<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Androgen insensitivity syndrome and can you explain it in depth? [/INST] Androgen insensitivity syndrome (AIS) is a difference in sex development involving hormonal resistance due to androgen receptor dysfunction.It affects 1 in 20,000 to 64,000 XY (karyotypically male) births. The condition results in the partial or complete inability of cells to respond to androgens. This unresponsiveness can impair or prevent the development of male genitals, as well as impairing or preventing the development of male secondary sexual characteristics at puberty. It does not significantly impair female genital or sexual development. The insensitivity to androgens is therefore clinically significant only when it occurs in genetic males, (i.e. individuals with a Y-chromosome, or more specifically, an SRY gene).  Clinical phenotypes in these individuals range from a typical male habitus with mild spermatogenic defect or reduced secondary terminal hair, to a full female habitus, despite the presence of a Y-chromosome.AIS is divided into three categories that are differentiated by the degree of genital masculinization: complete androgen insensitivity syndrome (CAIS) is indicated when the external genitalia are those of a typical female; mild androgen insensitivity syndrome (MAIS) is indicated when the external genitalia are those of a typical male, and partial androgen insensitivity syndrome (PAIS) is indicated when the external genitalia are partially, but not fully, masculinized. Androgen insensitivity syndrome is the largest single entity that leads to 46,XY undermasculinized genitalia.Management of AIS is currently limited to symptomatic management; no method is currently available to correct the malfunctioning androgen receptor proteins produced by AR gene mutations.  Areas of management include sex assignment, genitoplasty, gonadectomy to reduce tumor risk, hormone replacement therapy, genetic counseling, and psychological counseling.

Genetics
The human androgen receptor (AR) is a protein encoded by a gene located on the proximal long arm of the X chromosome (locus Xq11-Xq12).  The protein coding region consists of approximately 2,757 nucleotides (919 codons) spanning eight exons, designated 1-8 or A-H.  Introns vary in size between 0.7 and 26 kb.  Like other nuclear receptors, the AR protein consists of several functional domains: the transactivation domain (also called the transcription-regulation domain or the amino / NH2-terminal domain), the DNA-binding domain, the hinge region, and the steroid-binding domain (also called the carboxyl-terminal ligand-binding domain).  The transactivation domain is encoded by exon 1, and makes up more than half of the AR protein.  Exons 2 and 3 encode the DNA-binding domain, while the 5 portion of exon 4 encodes the hinge region.  The remainder of exons 4 through 8 encodes the ligand binding domain.

Trinucleotide satellite lengths and AR transcriptional activity
The AR gene contains two polymorphic trinucleotide microsatellites in exon 1.  The first microsatellite (nearest the 5 end) contains 8  to 60  repetitions of the glutamine codon "CAG" and is thus known as the polyglutamine tract.  The second microsatellite contains 4  to 31  repetitions of the glycine codon "GGC" and is known as the polyglycine tract.  The average number of repetitions varies by ethnicity, with Caucasians exhibiting an average of 21 CAG repeats, and Blacks 18.  In men, disease states are associated with extremes in polyglutamine tract length; prostate cancer, hepatocellular carcinoma, and intellectual disability are associated with too few repetitions, while spinal and bulbar muscular atrophy (SBMA) is associated with a CAG repetition length of 40 or more.  Some studies indicate that the length of the polyglutamine tract is inversely correlated with transcriptional activity in the AR protein, and that longer polyglutamine tracts may be associated with male infertility and undermasculinized genitalia in men.  However, other studies have indicated no such correlation exists. A comprehensive meta-analysis of the subject published in 2007 supports the existence of the correlation, and concluded these discrepancies could be resolved when sample size and study design are taken into account.  Some studies suggest longer polyglycine tract lengths are also associated with genital masculinization defects in men.  Other studies find no such association.

AR mutations
As of 2010, over 400 AR mutations have been reported in the AR mutation database, and the number continues to grow.  Inheritance is typically maternal and follows an X-linked recessive pattern; individuals with a 46,XY karyotype always express the mutant gene since they have only one X chromosome, whereas 46,XX carriers are minimally affected.  About 30% of the time, the AR mutation is a spontaneous result, and is not inherited.  Such de novo mutations are the result of a germ cell mutation or germ cell mosaicism in the gonads of one of the parents, or a mutation in the fertilized egg itself.  In one study, three of eight de novo mutations occurred in the postzygotic stage, leading to the estimate that up to one-third of de novo mutations result in somatic mosaicism.  Not every mutation of the AR gene results in androgen insensitivity; one particular mutation occurs in 8 to 14% of genetic males, and is thought to adversely affect only a small number of individuals when other genetic factors are present.

Other causes
Some individuals with CAIS or PAIS do not have any AR mutations despite clinical, hormonal, and histological features sufficient to warrant an AIS diagnosis; up to 5% of women with CAIS do not have an AR mutation, as well as between 27 and 72% of individuals with PAIS.
In one patient, the underlying cause for presumptive PAIS was a mutant steroidogenic factor-1 (SF-1) protein.  In another patient, CAIS was the result of a deficit in the transmission of a transactivating signal from the N-terminal region of the androgen receptor to the basal transcription machinery of the cell.  A coactivator protein interacting with the activation function 1 (AF-1) transactivation domain of the androgen receptor may have been deficient in this patient.  The signal disruption could not be corrected by supplementation with any coactivators known at the time, nor was the absent coactivator protein characterized, which left some in the field unconvinced that a mutant coactivator would explain the mechanism of androgen resistance in CAIS or PAIS patients with a typical AR gene.

XY karyotype
Depending on the mutation, a person with a 46,XY karyotype and AIS can have either a male (MAIS) or female (CAIS) phenotype, or may have genitalia that are only partially masculinized (PAIS).  The gonads are testes regardless of phenotype due to the influence of the Y chromosome.  A 46,XY female, thus, does not have ovaries, and can not contribute an egg towards conception. In some cases, 46, XY females do form a vestigial uterus and have been able to gestate a children. Such examples are rare and have required the use of an egg donor, hormone therapy, and IVF.Several case studies of fertile 46,XY males with AIS have been published, although this group is thought to be a minority.  In some cases, infertile males with MAIS have been able to conceive children after increasing their sperm count through the use of supplementary testosterone.A genetic male conceived by a man with AIS would not receive his fathers X chromosome,  thus would neither inherit nor carry the gene for the syndrome.  A genetic female conceived in such a way would receive her fathers X chromosome, thus would become a carrier.

XX karyotype
Genetic females (46,XX karyotype) have two X chromosomes, thus have two AR genes.  A mutation in one (but not both) results in a minimally affected, fertile, female carrier.  Some carriers have been noted to have slightly reduced body hair, delayed puberty, and/or tall stature, presumably due to skewed X-inactivation.  A female carrier will pass the affected AR gene to her children 50% of the time.  If the affected child is a genetic female, she, too, will be a carrier.  An affected 46,XY child will have AIS.A genetic female with mutations in both AR genes could theoretically result from the union of a fertile man with AIS and a female carrier of the gene, or from de novo mutation.  However, given the scarcity of fertile AIS men and low incidence of AR mutation, the chances of this occurrence are small.  The phenotype of such an individual is a matter of speculation; as of 2010, no such documented case has been published.

Correlation of genotype and phenotype
Individuals with partial AIS, unlike those with the complete or mild forms, present at birth with ambiguous genitalia, and the decision to raise the child as male or female is often not obvious.  Unfortunately,  little information regarding phenotype can be gleaned from precise knowledge of the AR mutation itself;  the same AR mutation may cause significant variation in the degree of masculinization in different individuals, even among members of the same family. Exactly what causes this variation is not entirely understood, although factors contributing to it could include the lengths of the polyglutamine and polyglycine tracts, sensitivity to and variations in the intrauterine endocrine milieu, the effect of coregulatory proteins active in Sertoli cells, somatic mosaicism, expression of the 5RD2 gene in genital skin fibroblasts, reduced AR transcription and translation from factors other than mutations in the AR coding region, an unidentified coactivator protein, enzyme deficiencies such as 21-hydroxylase deficiency, or other genetic variations such as a mutant steroidogenic factor-1 protein.  The degree of variation, however, does not appear to be constant across all AR mutations, and is much more extreme in some.  Missense mutations that result in a single amino acid substitution are known to produce the most phenotypic diversity.

Pathophysiology
Androgens and the androgen receptor
The effects that androgens have on the human body (virilization, masculinization, anabolism, etc.) are not brought about by androgens themselves, but rather are the result of androgens bound to androgen receptors; the androgen receptor mediates the effects of androgens in the human body.  Likewise, the androgen receptor itself is generally inactive in the cell until androgen binding occurs.The following series of steps illustrates how androgens and the androgen receptor work together to produce androgenic effects:

In this way, androgens bound to androgen receptors regulate the expression of target genes, thus produce androgenic effects.Theoretically, certain mutant androgen receptors can function without androgens; in vitro studies have demonstrated that a mutant androgen receptor protein can induce transcription in the absence of androgen if its steroid binding domain is deleted.  Conversely, the steroid-binding domain may act to repress the AR transactivation domain, perhaps due to the ARs unliganded conformation.

Androgens in fetal development
Human embryos develop similarly for the first six weeks, regardless of genetic sex (46,XX or 46,XY karyotype); the only way to tell the difference between 46,XX or 46,XY embryos during this time period is to look for Barr bodies or a Y chromosome.  The gonads begin as bulges of tissue called the genital ridges at the back of the abdominal cavity, near the midline.  By the fifth week, the genital ridges differentiate into an outer cortex and an inner medulla, and are called indifferent gonads.  By the sixth week, the indifferent gonads begin to differentiate according to genetic sex.  If the karyotype is 46,XY, testes develop due to the influence of the Y chromosome’s SRY gene.  This process does not require the presence of androgen, nor a functional androgen receptor.Until around the seventh week of development, the embryo has indifferent sex accessory ducts, which consist of two pairs of ducts: the Müllerian ducts and the Wolffian ducts.  Sertoli cells within the testes secrete anti-Müllerian hormone around this time to suppress the development of the Müllerian ducts, and cause their degeneration.  Without this anti-Müllerian hormone, the Müllerian ducts develop into the female internal genitalia (uterus, cervix, fallopian tubes, and upper vaginal barrel).  Unlike the Müllerian ducts, the Wolffian ducts will not continue to develop by default.  In the presence of testosterone and functional androgen receptors, the Wolffian ducts develop into the epididymides, vasa deferentia, and seminal vesicles.  If the testes fail to secrete testosterone, or the androgen receptors do not function properly, the Wolffian ducts degenerate.

Masculinization of the male external genitalia (the penis, penile urethra, and scrotum), as well as the prostate, are dependent on the androgen dihydrotestosterone.  Testosterone is converted into dihydrotestosterone by the 5-alpha reductase enzyme.  If this enzyme is absent or deficient, then dihydrotestosterone is not created, and the external male genitalia do not develop properly.  As is the case with the internal male genitalia, a functional androgen receptor is needed for dihydrotestosterone to regulate the transcription of target genes involved in development.

Pathogenesis of AIS
Mutations in the androgen receptor gene can cause problems with any of the steps involved in androgenization, from the synthesis of the androgen receptor protein itself, through the transcriptional ability of the dimerized, androgen-AR complex.  AIS can result if even one of these steps is significantly disrupted, as each step is required for androgens to activate the AR successfully and regulate gene expression.  Exactly which steps a particular mutation will impair can be predicted, to some extent, by identifying the area of the AR in which the mutation resides.  This predictive ability is primarily retrospective in origin; the different functional domains of the AR gene have been elucidated by analyzing the effects of specific mutations in different regions of the AR.  For example, mutations in the steroid binding domain have been known to affect androgen binding affinity or retention, mutations in the hinge region have been known to affect nuclear translocation, mutations in the DNA-binding domain have been known to affect dimerization and binding to target DNA, and mutations in the transactivation domain have been known to affect target gene transcription regulation.  Unfortunately, even when the affected functional domain is known, predicting the phenotypical consequences of a particular mutation (see Correlation of genotype and phenotype) is difficult.Some mutations can adversely impact more than one functional domain.  For example, a mutation in one functional domain can have deleterious effects on another by altering the way in which the domains interact.  A single mutation can affect all downstream functional domains if a premature stop codon or framing error results; such a mutation can result in a completely unusable (or unsynthesizable) androgen receptor protein.  The steroid binding domain is particularly vulnerable to the effects of a premature stop codon or framing error, since it occurs at the end of the gene, and its information is thus more likely to be truncated or misinterpreted than other functional domains.Other, more complex relationships have been observed as a consequence of mutated AR; some mutations associated with male phenotypes have been linked to male breast cancer, prostate cancer, or in the case of spinal and bulbar muscular atrophy, disease of the central nervous system.  The form of breast cancer seen in some men with PAIS is caused by a mutation in the ARs DNA-binding domain.  This mutation is thought to cause a disturbance of the ARs target gene interaction that allows it to act at certain additional targets, possibly in conjunction with the estrogen receptor protein, to cause cancerous growth. The pathogenesis of spinal and bulbar muscular atrophy (SBMA) demonstrates that even the mutant AR protein itself can result in pathology.  The trinucleotide repeat expansion of the polyglutamine tract of the AR gene that is associated with SBMA results in the synthesis of a misfolded AR protein that the cell fails to proteolyze and disperse properly.  These misfolded AR proteins form aggregates in the cell cytoplasm and nucleus.  Over the course of 30 to 50 years, these aggregates accumulate and have a cytotoxic effect, eventually resulting in the neurodegenerative symptoms associated with SBMA.

Diagnosis
The phenotypes that result from the insensitivity to androgens are not unique to AIS, thus the diagnosis of AIS requires thorough exclusion of other causes.  Clinical findings indicative of AIS include the presence of a short vagina  or undermasculinized genitalia, partial or complete regression of Müllerian structures, bilateral nondysplastic testes, and impaired spermatogenesis and/or virilization.  Laboratory findings include a 46,XY karyotype and typical or elevated postpubertal testosterone, luteinizing hormone, and estradiol levels.  The androgen binding activity of genital skin fibroblasts is typically diminished, although exceptions have been reported.  Conversion of testosterone to dihydrotestosterone may be impaired.  The diagnosis of AIS is confirmed if androgen receptor gene sequencing reveals a mutation, although not all individuals with AIS (particularly PAIS) will have an AR mutation (see Other Causes).Each of the three types of AIS (complete, partial, and mild) has a different list of differential diagnoses to consider.  Depending on the form of AIS suspected, the list of differentials can include:

Classification
AIS is broken down into three classes based on phenotype: complete androgen insensitivity syndrome (CAIS), partial androgen insensitivity syndrome (PAIS), and mild androgen insensitivity syndrome (MAIS).  A supplemental system of phenotypic grading that uses seven classes instead of the traditional three was proposed by pediatric endocrinologist Charmian A. Quigley et al. in 1995.  The first six grades of the scale, grades 1 through 6, are differentiated by the degree of genital masculinization; grade 1 is indicated when the external genitalia is fully masculinized, grade 6 is indicated when the external genitalia is fully feminized, and grades 2 through 5 quantify four degrees of decreasingly masculinized genitalia that lie in the interim.  Grade 7 is indistinguishable from grade 6 until puberty, and is thereafter differentiated by the presence of secondary terminal hair; grade 6 is indicated when secondary terminal hair is present, whereas grade 7 is indicated when it is absent.  The Quigley scale can be used in conjunction with the traditional three classes of AIS to provide additional information regarding the degree of genital masculinization, and is particularly useful when the diagnosis is PAIS.

Complete AIS
Partial AIS
Mild AIS
Management
Management of AIS is currently limited to symptomatic management; no method is currently available to correct the malfunctioning androgen receptor proteins produced by AR gene mutations.  Areas of management include sex assignment, genitoplasty, gonadectomy in relation to tumor risk, hormone replacement therapy, genetic counseling, and psychological counseling.

CAIS
PAIS
MAIS
Epidemiology
AIS represents about 15% to 20% of DSDs and affects 1 in 20,000 to 1 in 64,000 males.Estimates for the incidence of androgen insensitivity syndrome are based on a relatively small population size, thus are known to be imprecise.  CAIS is estimated to occur in one of every 20,400 46,XY births.  A nationwide survey in the Netherlands based on patients with genetic confirmation of the diagnosis estimates that the minimal incidence of CAIS is one in 99,000.  The incidence of PAIS is estimated to be one in 130,000.  Due to its subtle presentation, MAIS is not typically investigated except in the case of male infertility, thus its true prevalence is unknown.

Controversy
Preimplantation genetic diagnosis
Preimplantation genetic diagnosis (PGD or PIGD) refers to genetic profiling of embryos prior to implantation (as a form of embryo profiling), and sometimes even of oocytes prior to fertilization. When used to screen for a specific genetic sequence, its main advantage is that it avoids selective pregnancy termination, as the method makes it highly likely that a selected embryo will be free of the condition under consideration.In the UK, AIS appears on a list of serious genetic diseases that may be screened for via PGD.  Some ethicists, clinicians, and intersex advocates have argued that screening embryos to specifically exclude intersex traits is based on social and cultural norms as opposed to medical necessity.

History
Recorded descriptions of the effects of AIS date back hundreds of years, although significant understanding of its underlying histopathology did not occur until the 1950s.  The taxonomy and nomenclature associated with androgen insensitivity went through a significant evolution that paralleled this understanding.

Timeline of major milestones
1950: Lawson Wilkins administers daily methyltestosterone to a karyotype|46,XY female patient, who shows no signs of virilization.  His experiment is the first documented demonstration of the pathophysiology of AIS.
1970: Mary F. Lyon and Susan Hawkes reported that a gene on the X chromosome caused complete insensitivity to androgens in mice.
1981: Barbara Migeon et al. narrowed down the locus of the human androgen receptor gene (or a factor controlling the androgen receptor gene) to somewhere between Xq11 and Xq13.
1988: The human androgen receptor gene is first cloned and partially analyzed by multiple parties.  Terry Brown et al. reported the first mutations proven to cause AIS.
1989: Terry Brown et al. reported the exact locus of the AR gene (Xq11-Xq12), and Dennis Lubahn et al. published its intron-exon boundaries.
1994: The androgen receptor gene mutations database was created to provide a comprehensive listing of mutations published in medical journals and conference proceedings.

Early terminology
The first descriptions of the effects of AIS appeared in the medical literature as individual case reports or as part of a comprehensive description of intersex physicalities.  In 1839, Scottish obstetrician Sir James Young Simpson published one such description in an exhaustive study of intersexuality that has been credited with advancing the medical communitys understanding of the subject.  Simpsons system of taxonomy, however, was far from the first; taxonomies or descriptions for the classification of intersexuality were developed by Italian physician and physicist Fortuné Affaitati in 1549, French surgeon Ambroise Paré in 1573, French physician and sexology pioneer Nicolas Venette in 1687 (under the pseudonym Vénitien Salocini), and French zoologist Isidore Geoffroy Saint-Hilaire in 1832.  All five of these authors used the colloquial term "hermaphrodite" as the foundation of their taxonomies, although Simpson himself questioned the propriety of the word in his publication.  Use of the word "hermaphrodite" in the medical literature has persisted to this day, although its propriety is still in question.  An alternative system of nomenclature has been recently suggested, but the subject of exactly which word or words should be used in its place still one of much debate.

Pseudohermaphroditism
"Pseudohermaphroditism" has, until very recently, been the term used in the medical literature to describe the condition of an individual whose gonads and karyotype do not match the external genitalia in the gender binary sense.  For example, 46,XY individuals who have a female phenotype, but also have testes instead of ovaries—a group that includes all individuals with CAIS, as well as some individuals with PAIS—are classified as having "male pseudohermaphroditism", while individuals with both an ovary and a testis (or at least one ovotestis) are classified as having "true hermaphroditism".  Use of the word in the medical literature antedates the discovery of the chromosome,  thus its definition has not always taken karyotype into account when determining an individuals sex.  Previous definitions of "pseudohermaphroditism" relied on perceived inconsistencies between the internal and external organs; the "true" sex of an individual was determined by the internal organs, and the external organs determined the "perceived" sex of an individual.German-Swiss pathologist Edwin Klebs is sometimes noted for using the word "pseudohermaphroditism" in his taxonomy of intersexuality in 1876, although the word is clearly not his invention as is sometimes reported; the history of the word "pseudohermaphrodite" and the corresponding desire to separate "true" hermaphrodites from "false", "spurious", or "pseudo" hermaphrodites, dates back to at least 1709, when Dutch anatomist Frederik Ruysch used it in a publication describing a subject with testes and a mostly female phenotype.  "Pseudohermaphrodite" also appeared in the Acta Eruditorum later that same year, in a review of Ruyschs work.  Also some evidence indicates the word was already being used by the German and French medical community long before Klebs used it; German physiologist Johannes Peter Müller equated "pseudohermaphroditism" with a subclass of hermaphroditism from Saint-Hilaires taxonomy in a publication dated 1834, and by the 1840s "pseudohermaphroditism" was appearing in several French and German publications, including dictionaries.

Testicular feminization
In 1953, American gynecologist John Morris provided the first full description of what he called "testicular feminization syndrome" based on 82 cases compiled from the medical literature, including two of his own patients.  The term "testicular feminization" was coined to reflect Morris observation that the testicles in these patients produced a hormone that had a feminizing effect on the body, a phenomenon now understood to be due to the inaction of androgens, and subsequent aromatization of testosterone into estrogen.   A few years before Morris published his landmark paper, Lawson Wilkins had shown through experiment that unresponsiveness of the target cell to the action of androgenic hormones was a cause of "male pseudohermaphroditism".   Wilkins work, which clearly demonstrated the lack of a therapeutic effect when 46,XY patients were treated with androgens, caused a gradual shift in nomenclature from "testicular feminization" to "androgen resistance".

Other names
A distinct name has been given to many of the various presentations of AIS, such as Reifenstein syndrome (1947), Goldberg-Maxwell syndrome (1948), Morris syndrome (1953), Gilbert-Dreyfus syndrome (1957), Lubs syndrome (1959), "incomplete testicular feminization" (1963), Rosewater syndrome (1965), and Aimans syndrome (1979).  Since it was not understood that these different presentations were all caused by the same set of mutations in the androgen receptor gene, a unique name was given to each new combination of symptoms, resulting in a complicated stratification of seemingly disparate disorders.Over the last 60 years, as reports of strikingly different phenotypes were reported to occur even among members of the same family, and as steady progress was made towards the understanding of the underlying molecular pathogenesis of AIS, these disorders were found to be different phenotypic expressions of one syndrome caused by molecular defects in the androgen receptor gene.AIS is now the accepted terminology for the syndromes resulting from unresponsiveness of the target cell to the action of androgenic hormones.  CAIS encompasses the phenotypes previously described by "testicular feminization", Morris syndrome, and Goldberg-Maxwell syndrome; PAIS includes Reifenstein syndrome, Gilbert-Dreyfus syndrome, Lubs syndrome, "incomplete testicular feminization", and Rosewater syndrome; and MAIS includes Aimans syndrome.The more virilized phenotypes of AIS have sometimes been described as "undervirilized male syndrome", "infertile male syndrome", "undervirilized fertile male syndrome", etc., before evidence was reported that these conditions were caused by mutations in the AR gene </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Conus medullaris and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Neutral lipid storage disease and can you explain it in depth? [/INST] Neutral lipid storage disease (also known as Chanarin–Dorfman syndrome) is a congenital autosomal recessive disorder characterized by accumulation of triglycerides in the cytoplasm of leukocytes[1], (Jordan’s Anomaly) muscle, liver, fibroblasts, and other tissues. It commonly occurs as one of two subtypes, cardiomyopathic neutral lipid storage disease (NLSD-M), or ichthyotic neutral lipid storage disease (NLSD-I) which is also known as Chanarin–Dorfman syndrome), which are characterized primarily by myopathy and ichthyosis, respectively. Normally, the ichthyosis that is present is typically non-bullous congenital ichthyosiform erythroderma which appears as white scaling.
It has been associated genetically with mutations in the CGI58 gene, (for NLSD-I), or the ATGL gene (for NLSD-M.)

Cause
Neutral lipid storage disease is caused by the abnormal and excessive accumulation of lipids in certain bodily tissues, including the liver, the heart, and muscle. Normally, these lipids are stored as lipid droplets and are normally used for metabolism, cell signaling and trafficking of vesicles. Neutral lipid storage disease is a disease that is diagnosed with the simultaneous occurrence of myopathy and/or  ichthyosis. Myopathy is defined as a disease of the muscle tissue. Ichthyosis is a skin related disease in which the skin becomes very scaly, thick, and dry.

Genetics
Neutral lipid storage disease (NLSD) occurs in one of two genetic and clinical subtypes. Both subtypes are autosomal recessive disorders, meaning that a mutant allele must be inherited from both parents in order to cause disease.Subtype I: Neutral Lipid Storage Disease with Myopathy (NLSD-M), is caused by a mutation in the PNPLA2 gene, which reduces the normal expression orfunction of the ATGL protein. PNPLA2 is located on chromosome 11. ATGL is an enzyme involved in catabolism of triglycerides (long-term fat storage) into fatty acids (short-term fat storage) within the body In the absence of fully functional ATGL, triglycerides accumulate in the bloodstream and bodily tissues. Interestingly, individuals with NLSD are not typically obese. It has been proposed that the assimilation, rather than degradation of triglycerides is the main factor in fat accumulation in adipose cells. In the absence of functional ATGL, triglycerides accumulate in the bloodstream and bodily tissues. Interestingly, individuals with NLSD are not typically obese. It has been proposed that the assimilation, rather than degradation of triglycerides is the main factor in fat accumulation in adipose cells.  Patients with NLSD-M display progressive skeletal myopathy and severe cardiomyopathy in ~40% of cases.  The pathophysiology and mechanistic basis of myopathy arising from deficits is lipid metabolism is not yet known.Subtype II:  Neutral Lipid Storage Disease with Ichthyosis (NLSD-I), or Chanarin-Dorfman syndrome, is caused by a mutation in the CGI-58 protein. CGI-58 is a coactivator of ATGL, and together these proteins sustain blood lipid levels between meals.  Disruption of CGI-58 gives rise to the symptoms of ichthyosis, a dermatological condition in which skin becomes very scaly, thick and dry.Ichthyosis is an inherited disorder, like NLSD, and has been found to be genetically linked in some situations with the PNPLA2 gene. Therefore, sometimes when there is a mutation in the PNPLA2 gene, the linked allele of CG-58 is mutated as well. This specific gene, however, does not produce ichthyosis on its own. Ichthyosis can be diagnosed individually in a patient and the genetic cause for unlinked ichthyosis is different from the gene linked with PNPLA2. Keep in mind these disorders may occur individually within a patient as well.

Pathophysiology
The functional changes that occur with this disease are mostly metabolic. Accumulation of triglycerides in the body without an efficient mode for catabolism is thought to lead to the eventual symptoms of this disease. Upon digestion and absorption of fat by the small intestine, triglycerides are combined with vitamins and cholesterol to form chylomicrons. Chylomicrons travel from the intestine into the lymph system before entering the bloodstream. Enzymatic catalysis of chylomicrons by lipases in the bloodstream enables the uptake of lipids and fatty acids by cells.  In individuals with NLSD, their triglycerides are not catabolized in the blood, and cells accumulate partially processed lipid droplets over time, which may lead to dysfunction in absorbing tissues. In affected individuals, muscle cells, fibroblasts, and leukocytes appear to be prone to the excessive accumulation of triglycerides as lipid droplets. Excessive accumulation of lipids in tissues not designed for long term storage may underlie the clinical manifestations of weakened skeletal and cardiac muscle, fatty liver, pancreatitis, hypothyroidism, and type 2 diabetes.

Diagnosis
Main physical signs include a fatty liver, a weakened and enlarged heart (cardiomyopathy), inflammation of the pancreas (pancreatitis), reduced thyroid activity (hypothyroidism), type 2 diabetes, abnormal levels of creatine kinase in blood, and increased weakness of proximal muscles due to fatty replacement of skeletal muscle fibers. Accurate diagnosis is complicated by symptomatic overlap with other disorders. One of the earliest symptoms to manifest clinically is peripheral limb weakness, which becomes progressively more severe over time. Specifically, asymmetric right shoulder weakness is an idiosyncratic hallmark of NLSD enabling it to be distinguished from myopathies arising from alternative muscular disorders.
NLSD is often diagnosed by the presence of lipid inclusions within leukocytes (Jordan’ Anomaly), which can be detected using histochemical and electron microscopy. Image B shows the characteristic lipid accumulation in red blood cells, in a NLSD patient, as compared to a normal individual (Image A).
Classically, NLSD is associated with myopathy and can, in some cases, be linked with icthyosis. Therefore, with these symptoms or diagnosis, it is likely that the patient could and would be diagnosed with NLSD.
Although lipid accumulation is most prominent in  myocytes, hepatocytes, and granulocytes, other tissues displayed elevated deposits as well. For the purpose of diagnosis, MRIs have been used to identify large fat deposits within muscle tissue.
People can live with NLSD, but there can be complications due to the affects this disease has on other major parts of the body like the liver, the heart, and skeletal muscle. Whereas myopathy won’t necessarily show up until a patient is in the third decade of their life, a child born with ichthyosis, is immediately evaluated for NLSD, in which it is detected very early on. Also, the earlier that NLSD can be detected and symptoms treated, the better quality of life the patient can have.

Treatment
Although there is no current treatment to correct the abnormal metabolic processes underlying this disease, there are approaches to ameliorate symptoms and decrease the effects of this disease. Because there is an increase of fat storage and a decrease in fat catabolism, low fat diets are recommended for slowing the progression of the disease, including the onset of type 2 diabetes and hypothyroidism. In addition, diets containing triglycerides composed of short chain fatty acids are more beneficial than TGAs containing long chain fatty acids. Ketone bodies can be rapidly transported, catabolized, and used by many tissues including the brain. Medium-chain fatty acids in an individual’s diet are rapidly used by the body, limiting storage and therefore alleviating lipid droplet accumulation. Foods with medium-chain fatty acids include dairy, fat and coconut oil. Supplements can also be taken to increase uptake of these fatty acids. Triaheptanoin, a triglyceride containing three seven-carbon chain fatty acids, has also been proposed as a possible dietary supplement </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Keratitis and can you explain it in depth? [/INST] Keratitis is a condition in which the eyes cornea, the clear dome on the front surface of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves any of the following symptoms: pain, impaired eyesight, photophobia (light sensitivity), red eye and a gritty sensation.

Classification (by chronicity)
Acute
Acute epithelial keratitis
Nummular keratitis
Interstitial keratitis
Disciform keratitis

Chronic
Neurotrophic keratitis
Mucous plaque keratitis

Classification (infective)
Viral
Herpes simplex keratitis (dendritic keratitis). Viral infection of the cornea is often caused by the herpes simplex virus (HSV) which frequently leaves what is called a dendritic ulcer.
Herpes zoster keratitis, associated with herpes zoster ophthalmicus, which is a form of shingles.

Bacterial
Bacterial keratitis. Bacterial infection of the cornea can follow from an injury or from wearing contact lenses. The bacteria involved are Staphylococcus aureus and for contact lens wearers, Pseudomonas aeruginosa. Pseudomonas aeruginosa contains enzymes that can digest the cornea.

Fungal
Fungal keratitis, caused by Aspergillus fumigatus and Candida albicans (cf. Fusarium, causing an outbreak of keratitis in 2005–2006 through the possible vector of Bausch & Lomb ReNu with MoistureLoc contact lens solution)

Amoebic
Acanthamoebic keratitis
Amoebic infection of the cornea is a serious corneal infection, often affecting contact lens wearers. It is usually caused by Acanthamoeba. On May 25, 2007, the U.S </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Warfarin necrosis and can you explain it in depth? [/INST] Warfarin-induced skin necrosis is a condition in which skin and subcutaneous tissue necrosis (tissue death) occurs due to acquired protein C deficiency following treatment with anti-vitamin K anticoagulants (4-hydroxycoumarins, such as warfarin).Warfarin necrosis is a rare but severe complication of treatment with warfarin or related anticoagulants. The typical patient appears to be an obese, middle aged woman (median age 54 years, male to female ratio 1:3).: 122–3  This drug eruption usually occurs between the third and tenth days of therapy with warfarin derivatives. The first symptoms are pain and redness in the affected area. As they progress, lesions develop a sharp border and become petechial, then hard and purpuric. They may then resolve or progress to form large, irregular, bloody bullae with eventual necrosis and slow-healing eschar formation. Favored sites are breasts, thighs, buttocks and penis, all areas with subcutaneous fat.: 122   In rare cases, the fascia and muscle are involved.Development of the syndrome is associated with the use of large loading doses at the start of treatment.

Mechanism
Warfarin necrosis usually occurs three to five days after drug therapy is begun, and a high initial dose increases the risk of its development.: 122   Warfarin-induced necrosis can develop both at sites of local injection and - when infused intravenously - in a widespread pattern.: 123 In warfarins initial stages of action, inhibition of protein C and Factor VII is stronger than inhibition of the other vitamin K-dependent coagulation factors II, IX, and X. This results from the fact that these proteins have different half-lives: 1.5 to six hours for factor VII and eight hours for protein C, versus one day for factor IX, two days for factor X and two to five days for factor II. The larger the initial dose of vitamin K-antagonist, the more pronounced these differences are </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is SERKAL syndrome and can you explain it in depth? [/INST] SERKAL syndrome (SEx Reversion, Kidneys, Adrenal and Lung dysgenesis) is an autosomal recessive disorder in XX humans </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is CRLF1 and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Overriding aorta and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hereditary sensory and autonomic neuropathy and can you explain it in depth? [/INST] Hereditary sensory and autonomic neuropathy (HSAN) or hereditary sensory neuropathy (HSN) is a condition used to describe any of the types of this disease which inhibit sensation.
They are less common than Charcot-Marie-Tooth disease.

Classification
Eight different clinical entities have been described under hereditary sensory and autonomic neuropathies – all characterized by progressive loss of function that predominantly affects the peripheral sensory nerves. Their incidence has been estimated to be about 1 in 250,000.

Type 1
Hereditary sensory neuropathy type 1 is a condition characterized by nerve abnormalities in the legs and feet (peripheral neuropathy). Many people with this condition have tingling, weakness, and a reduced ability to feel pain and sense hot and cold. Some affected individuals do not lose sensation, but instead feel shooting pains in their legs and feet. As the disorder progresses, the sensory abnormalities can affect the hands, arms, shoulders, and abdomen. Affected individuals may also experience muscle wasting and weakness as they get older, but this varies widely within families.
Affected individuals typically get open sores (ulcers) on their feet or hands or infections of the soft tissue of the fingertips (whitlows) that are slow to heal. Because affected individuals cannot feel the pain of these sores, they may not seek treatment right away. Without treatment, the ulcers can become infected and may require amputation of the surrounding area.
Albeit rarely, people with hereditary sensory neuropathy type 1 may develop hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss).
The signs and symptoms of hereditary sensory neuropathy type 1 typically appear during a persons teens or twenties. While the features of this disorder tend to worsen over time, affected individuals have a normal life expectancy if signs and symptoms are properly treated.
Type 1 is the most common form among the 5 types of HSAN. Its historical names include mal perforant du pied, ulcero-mutilating neuropathy, hereditary perforating ulcers, familial trophoneurosis, familial syringomyelia, hereditary sensory radicular neuropathy, among others. This type includes a popular disease Charcot-Marie-Tooth type 2B syndrome (HMSN 2B). that is also named as HSAN sub-type 1C.
Type 1 is inherited as an autosomal dominant trait. The disease usually starts during early adolescence or adulthood. The disease is characterized by the loss of pain sensation mainly in the distal parts of the lower limbs; that is, in the parts of the legs farther away from the center of the body. Since the affected individuals cannot feel pain, minor injuries in this area may not be immediately recognized and may develop into extensive ulcerations. Once infection occurs, further complications such as progressive destruction of underlying bones may follow and may necessitate amputation. In rare cases, the disease is accompanied with nerve deafness and muscle wasting. Autonomic disturbance, if present, appears as anhidrosis, a sweating abnormality. Examinations of the nerve structure and function showed signs of neuronal degeneration such as a marked reduction in the number of myelinated fibers and axonal loss. Sensory neurons lose the ability to transmit signals, while motor neurons has reduced ability to transmit signals.Genes related to Hereditary sensory and autonomic neuropathy Type 1:
Mutations in the SPTLC1 gene cause hereditary sensory neuropathy type 1. The SPTLC1 gene provides instructions for making one part (subunit) of an enzyme called serine palmitoyltransferase (SPT). The SPT enzyme is involved in making certain fats called sphingolipids. Sphingolipids are important components of cell membranes and play a role in many cell functions.
SPTLC1 gene mutations reduce the amount of SPTLC1 subunit that is produced and result in an SPT enzyme with decreased function. A lack of functional SPT enzyme leads to a decrease in sphingolipid production and a harmful buildup of certain byproducts. Sphingolipids are found in myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. A decrease in sphingolipids disrupts the formation of myelin, causing nerve cells to become less efficient and eventually die. When sphingolipids are not made, an accumulation of toxic byproducts can also lead to nerve cell death. This gradual destruction of nerve cells results in loss of sensation and muscle weakness in people with hereditary sensory neuropathy type 1.

Type 2, Congenital sensory neuropathy
Hereditary sensory and autonomic neuropathy type II (HSAN2) is a condition that primarily affects the sensory nerve cells (sensory neurons) which transmit information about sensations such as pain, temperature, and touch. These sensations are impaired in people with HSAN2. In some affected people, the condition may also cause mild abnormalities of the autonomic nervous system, which controls involuntary body functions such as heart rate, digestion, and breathing. The signs and symptoms of HSAN2 typically begin in infancy or early childhood.
The first sign of HSAN2 is usually numbness in the hands and feet. Soon after, affected individuals lose the ability to feel pain or sense hot and cold. People with HSAN2 often develop open sores (ulcers) on their hands and feet. Because affected individuals cannot feel the pain of these sores, they may not seek treatment right away. Without treatment, the ulcers can become infected and may lead to amputation of the affected area. Unintentional self-injury is common in people with HSAN2, typically by biting the tongue, lips, or fingers. These injuries may lead to spontaneous amputation of the affected areas. Affected individuals often have injuries and fractures in their hands, feet, limbs, and joints that go untreated because of the inability to feel pain. Repeated injury can lead to a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed.
The effects of HSAN2 on the autonomic nervous system are more variable. Some infants with HSAN2 have trouble sucking, which makes it difficult for them to eat. People with HSAN2 may experience episodes in which breathing slows or stops for short periods (apnea); digestive problems such as the backflow of stomach acids into the esophagus (gastroesophageal reflux); or slow eye blink or gag reflexes. Affected individuals may also have weak deep tendon reflexes, such as the reflex being tested when a doctor taps the knee with a hammer.
Some people with HSAN2 experience a diminished sense of taste due to the loss of a type of taste bud on the tip of the tongue called lingual fungiform papillae.
Type 2, congenital sensory neuropathy (also historically known as Morvans disease), is characterized by onset of symptoms in early infancy or childhood. Upper & lower extremities are affected with chronic ulcerations and multiple injuries to fingers and feet. Pain sensation is affected predominantly and deep tendon reflexes are reduced. Autoamputation of the distal phalanges is common and so is neuropathic joint degeneration. The NCV shows reduced or absent sensory nerve action potentials and nerve biopsy shows total loss of myelinated fibers and reduced numbers of unmyelinated fibers. It is inherited as an autosomal recessive condition.
Genes related to Hereditary sensory and autonomic neuropathy Type 2:
There are two types of HSAN2, called HSAN2A and HSAN2B, each caused by mutations in a different gene. HSAN2A is caused by mutations in the WNK1 gene, and HSAN2B is caused by mutations in the RETREG1 gene (FAM134B). Although two different genes are involved, the signs and symptoms of HSAN2A and HSAN2B are the same.
The WNK1 gene provides instructions for making multiple versions (isoforms) of the WNK1 protein. HSAN2A is caused by mutations that affect a particular isoform called the WNK1/HSN2 protein. This protein is found in the cells of the nervous system, including nerve cells that transmit the sensations of pain, temperature, and touch (sensory neurons). The mutations involved in HSAN2A result in an abnormally short WNK1/HSN2 protein. Although the function of this protein is unknown, it is likely that the abnormally short version cannot function properly. People with HSAN2A have a reduction in the number of sensory neurons; however, the role that WNK1/HSN2 mutations play in that loss is unclear.
HSAN2B is caused by mutations in the RETREG1 gene. These mutations may lead to an abnormally short and nonfunctional protein. The RETREG1 protein is found in sensory and autonomic neurons. It is involved in the survival of neurons, particularly those that transmit pain signals, which are called nociceptive neurons. When the RETREG1 protein is nonfunctional, neurons die by a process of self-destruction called apoptosis.
The loss of neurons leads to the inability to feel pain, temperature, and touch sensations and to the impairment of the autonomic nervous system seen in people with HSAN2.

Type 3, Familial dysautonomia
Familial dysautonomia is a genetic disorder that affects the development and survival of certain nerve cells. The disorder disturbs cells in the autonomic nervous system, which controls involuntary actions such as digestion, breathing, production of tears, and the regulation of blood pressure and body temperature. It also affects the sensory nervous system, which controls activities related to the senses, such as taste and the perception of pain, heat, and cold. Familial dysautonomia is also called hereditary sensory and autonomic neuropathy, type III.
Problems related to this disorder first appear during infancy. Early signs and symptoms include poor muscle tone (hypotonia), feeding difficulties, poor growth, lack of tears, frequent lung infections, and difficulty maintaining body temperature. Older infants and young children with familial dysautonomia may hold their breath for prolonged periods of time, which may cause a bluish appearance of the skin or lips (cyanosis) or fainting. This breath-holding behavior usually stops by age 6. Developmental milestones, such as walking and speech, are usually delayed, although some affected individuals show no signs of developmental delay.
Additional signs and symptoms in school-age children include bed wetting, episodes of vomiting, reduced sensitivity to temperature changes and pain, poor balance, abnormal curvature of the spine (scoliosis), poor bone quality and increased risk of bone fractures, and kidney and heart problems. Affected individuals also have poor regulation of blood pressure. They may experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting. They can also have episodes of high blood pressure when nervous or excited, or during vomiting incidents. About one-third of children with familial dysautonomia have learning disabilities, such as a short attention span, that require special education classes. By adulthood, affected individuals often have increasing difficulties with balance and walking unaided. Other problems that may appear in adolescence or early adulthood include lung damage due to repeated infections, impaired kidney function, and worsening vision due to the shrinking size (atrophy) of optic nerves, which carry information from the eyes to the brain.
Type 3, familial dysautonomia (FD) or Riley-Day syndrome, is an autosomal recessive disorder seen predominantly in Jews of eastern European descent. Patients present with sensory and autonomic disturbances. Newborns have absent or weak suck reflex, hypotonia and hypothermia. Delayed physical development, poor temperature and motor incoordination are seen in early childhood. Other features include reduced or absent tears, depressed deep tendon reflexes, absent corneal reflex, postural hypotension and relative indifference to pain. Scoliosis is frequent. Intelligence remains normal. Many patients die in infancy and childhood. Lack of flare with intradermal histamine is seen. Histopathology of peripheral nerve shows reduced number of myelinated and non-myelinated axons. The catecholamine endings are absent.
Genes related to Hereditary sensory and autonomic neuropathy Type 3:
Mutations in the IKBKAP gene cause familial dysautonomia.
The IKBKAP gene provides instructions for making a protein called IKK complex-associated protein (IKAP). This protein is found in a variety of cells throughout the body, including brain cells.
Nearly all individuals with familial dysautonomia have two copies of the same IKBKAP gene mutation in each cell. This mutation can disrupt how information in the IKBKAP gene is pieced together to make a blueprint for the production of IKAP protein. As a result of this error, a reduced amount of normal IKAP protein is produced. This mutation behaves inconsistently, however. Some cells produce near normal amounts of the protein, and other cells—particularly brain cells—have very little of the protein. Critical activities in brain cells are probably disrupted by reduced amounts or the absence of IKAP protein, leading to the signs and symptoms of familial dysautonomia.

Type 4, Congenital insensitivity to pain with anhidrosis
Congenital insensitivity to pain with anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy type IV (HSAN IV), is characterized by insensitivity to pain, anhidrosis (the inability to sweat), and intellectual disability. The ability to sense all pain (including visceral pain) is absent, resulting in repeated injuries including: oral self-mutilation (biting of tongue, lips, and buccal mucosa); biting of fingertips; bruising, scarring, and infection of the skin; multiple bone fractures (many of which fail to heal properly); and recurrent joint dislocations resulting in joint deformity. Sense of touch, vibration, and position are normal. Anhidrosis predisposes to recurrent febrile episodes that are often the initial manifestation of CIPA. Hypothermia in cold environments also occurs. Intellectual disability of varying degree is observed in most affected individuals; hyperactivity and emotional lability are common.
Hereditary sensory neuropathy type IV (HSN4) is a rare genetic disorder characterized by the loss of sensation (sensory loss), especially in the feet and legs and, less severely, in the hands and forearms. The sensory loss is due to abnormal functioning of small, unmyelinated nerve fibers and portions of the spinal cord that control responses to pain and temperature as well as other involuntary or automatic body processes. Sweating is almost completely absent with this disorder. Intellectual disability is usually present.
Type 4, congenital insensitivity to pain with anhidrosis (CIPA), is an autosomal recessive condition and affected infants present with episodes of hyperthermia unrelated to environmental temperature, anhidrosis and insensitivity to pain. Palmar skin is thickened and charcot joints are commonly present. NCV shows motor and sensory nerve action potentials to be normal. The histopathology of peripheral nerve biopsy reveals absent small unmyelinated fibers and mitochondria are abnormally enlarged.
Management of Hereditary sensory and autonomic neuropathy Type 4:
Treatment of manifestations: Treatment is supportive and is best provided by specialists in pediatrics, orthopedics, dentistry, ophthalmology, and dermatology. For anhidrosis: Monitoring body temperature helps to institute timely measures to prevent/manage hyperthermia or hypothermia. For insensitivity to pain: Modify as much as reasonable a childs activities to prevent injuries. Inability to provide proper immobilization as a treatment for orthopedic injuries often delays healing; additionally, bracing and invasive orthopedic procedures increase the risk for infection. Methods used to prevent injuries to the lips, buccal mucosa, tongue, and teeth include tooth extraction, and/or filing (smoothing) of the sharp incisal edges of teeth, and/or use of a mouth guard. Skin care with moisturizers can help prevent palmar and plantar hyperkeratosis and cracking and secondary risk of infection; neurotrophic keratitis is best treated with routine care for dry eyes, prevention of corneal infection, and daily observation of the ocular surface. Interventions for behavioral, developmental and motor delays, as well as educational and social support for school-age children and adolescents, are recommended.
Prevention of secondary complications: Regular dental examinations and restriction of sweets to prevent dental caries; early treatment of dental caries and periodontal disease to prevent osteomyelitis of the mandible. During and following surgical procedures, potential complications to identify and manage promptly include hyper- or hypothermia and inadequate sedation, which may trigger unexpected movement and result in secondary injuries.

Type 5, Congenital insensitivity to pain with partial anhidrosis
Hereditary sensory and autonomic neuropathy type V (HSAN5) is a condition that primarily affects the sensory nerve cells (sensory neurons), which transmit information about sensations such as pain, temperature, and touch. These sensations are impaired in people with HSAN5.
The signs and symptoms of HSAN5 appear early, usually at birth or during infancy. People with HSAN5 lose the ability to feel pain, heat, and cold. Deep pain perception, the feeling of pain from injuries to bones, ligaments, or muscles, is especially affected in people with HSAN5. Because of the inability to feel deep pain, affected individuals suffer repeated severe injuries such as bone fractures and joint injuries that go unnoticed. Repeated trauma can lead to a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed.
Type 5, congenital insensitivity to pain with partial anhidrosis, also manifests with congenital insensitivity to pain & anhidrosis. There is a selective absence of small myelinated fibers differentiating it from Type IV (CIPA).
Genes related to Hereditary sensory and autonomic neuropathy Type 5:
Mutations in the NGF gene cause HSAN5. The NGF gene provides instructions for making a protein called nerve growth factor beta (NGFβ) that is important in the development and survival of nerve cells (neurons), including sensory neurons. The NGFβ protein functions by attaching (binding) to its receptors, which are found on the surface of neurons </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is IRAK4 and can you explain it in depth? [/INST] IRAK-4 (interleukin-1 receptor-associated kinase 4), in the IRAK family, is a protein kinase involved in signaling innate immune responses from Toll-like receptors. It also supports signaling from T-cell receptors. IRAK4 contains domain structures which are similar to those of IRAK1, IRAK2, IRAKM and Pelle. IRAK4 is unique compared to IRAK1, IRAK2 and IRAKM in that it functions upstream of the other IRAKs, but is more similar to Pelle in this trait. IRAK4 has important clinical applications.
Animals without IRAK-4 are more susceptible to viruses and bacteria but completely resistant to LPS challenge.

History
The first IL-1 receptor-associated kinase (IRAK) was observed in 1994 through experiments with murine T helper cell lines D10N and EL-4. Two years later the first experimental member of this family of kinases, IRAK1, was cloned. In 2002, through database searches at the National Center for Biotechnology Information in an attempt to recognize novel members of the IRAK family, a human cDNA sequence which encoded a peptide sharing significant homology with IRAK1 was identified. This cDNA sequence was found to have five amino acid substitutions compared to IRAK1 and was termed IRAK4.IRAK4 was proposed to be the mammalian homolog of the Pelle gene found in Drosophila melanogaster and was proposed to require its kinase activity in order for it to function in activating NF-κB. It was also proposed by Li et al. that it might function upstream of other IRAKs and possibly cause a cascade of phosphorylation events through its function as an IRAK1 kinase. This idea of a cascade of phosphorylation events was supported by a study where an IRAK4 knockout in mice showed a more severe phenotype than other IRAK knockout experiments and signalling through Toll/IL-1 receptor (TIR) is virtually eliminated.In 2007 it was found that IRAK4 activity was necessary for activating signal pathways which lead to mitogen-activated protein kinases (MAPK), or Toll-like receptor-mediated immune responses (TLR), but was not essential to T-cell Receptor (TCR) signalling as was originally proposed.

Protein structure
IRAK4 is a threonine/serine protein kinase made up of 460 amino acids, which contains both a kinase domain and a death domain. Its kinase domain exhibits the typical bilobed structure of kinases, with the N-terminal lobe consisting of a five-stranded antiparallel beta-sheet and one alpha helix. The C-terminal lobe is composed mainly of a number of alpha helices. Also contained within IRAK4s N-terminal is an extension of twenty amino acids, which is unique to IRAK4 among kinases, even within the IRAK family. Situated where the two lobes meet is an ATP binding site, which is covered by a tyrosine gatekeeper. Tyrosine as a gatekeeper is believed to be unique to the IRAK family of kinases. The protein also contains three auto-phosphorylation sites, each of which when mutated results in a decrease in the kinase activity of IRAK4.A structure of the autophosphorylation of the activation loop has been determined in which the activation loop Thr345 of one monomer is sitting in the active site of another monomer in the crystal (PDB: 4U9A, 4U97).

Function, mechanism, signalling pathway
Members of interleukin-1 receptor (Il-1R) and the Toll-like receptor superfamily share an intracytoplasmic Toll-IL-1 receptor (TIR) domain, which mediates recruitment of the interleukin-1 receptor-associated kinase (IRAK) complex via TIR-containing adapter molecules. The TIR-IRAK signaling pathway appears to be crucial for protective immunity against specific bacteria but is redundant against most other microorganisms. IRAK4 is considered the “master IRAK” in the mammalian IRAK family because it is the only component in the IL-1/TLR signalling pathway that is absolutely crucial to its functioning. When one of these pathways is stimulated, the cell is triggered to release proinflammatory signals and to trigger innate immune actions. The loss of IRAK4, or its intrinsic kinase activity, can entirely stop signalling through these pathways.IRAK4 is involved in signal transduction pathways stimulated by the cellular receptors belonging to the Toll/Interleukin-1 receptor superfamily. The Toll-Like Receptors (TLRs) are stimulated by recognition of pathogen-associated molecular patterns (PAMPS), whereas members of the IL-1R family are stimulated by cytokines.  Both play an essential role in the immune response. The ligand binding causes conformational changes to the intracellular domain which allows for the recruitment of scaffolding proteins. One of these proteins, MyD88, uses its death domains to recruit, orient, and activate IRAK4. IRAK2 can then be phosphorylated and joins with IRAK4 and MyD88 to form the myddosome complex, which further phosphorylates and recruits IRAK1. The myddosome complex and IRAK1 recruit and activate TNF receptor-associated factor 6 (TRAF6), a ubiquitin protein ligase. TRAF6 can polyubiquitinate IKK-γ as well as itself, which recruits TGF-β activated kinase 1 (TAK1) in order to activate its ability to phosphorylate IKK-β. These pathways both work to degrade IKKγ, which releases NFκB and free it for translocation into the nucleus. Additionally, TAK1 can activate JNK to induce a MAP kinase pathway which leads to AP-1-induced gene expression.  Together, AP-1 and NFκB lead to increased cytokine transcription, adhesion molecule production, and release of second messengers of infection.

Central to all of these signalling pathways is the kinase IRAK4. Results show that IRAK4 is a crucial component in an animals response to IL-1. Animals deficient in this kinase were found to be lacking in the ability to recognize viral and bacterial invaders, and were completely resistant to lethal doses of lipopolysaccharide (LPS). This is due to IRAK4s function as both a structural protein and as a kinase. Both of these functions are required for the myddosome complex formation. Additionally, IRAK4 has been shown to be absolutely essential in a TLR signalling.  IRAK4 deficient mice have a profoundly impaired ability to produce IL-6, TNF-α, and IL-12 in response to TLR ligands. However it is worthy of note that despite its importance to many immune signalling pathways, IRAK4 does not appear to be involved in TCR signalling.

Clinical significance
There are three components of evidence that illustrate IRAK4s involvement in TLR signalling. First, IRAK4 is the initial kinase near the TLR receptor to activate downstream effectors such as cytokines and chemokines in the inflammatory cascade. Second, deletion of the IRAK4 gene results in various cytokine response defects and finally, patients with IRAK4 deficiency have displayed defective immunity in response to IL-1, IL-8 and other TLR binding ligands. Considering IRAK4s downstream position of these signalling events, it is an important drug therapy target for various inflammatory disorders including rheumatoid arthritis, inflammatory bowel disease and other autoimmune diseases.

Prostate cancer
An important area of research currently being explored is the role the IRAK4 gene may play in the development of prostate cancer. There are several interacting factors that lead to the development of this disease however genetic susceptibility of chronic inflammation has been deemed one of the most important. It has been found that mutations in the IRAK4 gene can lead to dysfunctional TLR signalling and ultimately result in increased innate immune responses and therefore an increased inflammatory response. Over time, this can lead to the onset of prostate cancer.

Melanoma
Another interesting application of the IRAK4 gene was found in a study involving human melanoma patients </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Cutaneous actinomycosis and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Congenital contractural arachnodactyly and can you explain it in depth? [/INST] Congenital contractural arachnodactyly (CCA), also known as Beals-Hecht syndrome, is a rare autosomal dominant congenital connective tissue disorder. As with Marfan syndrome, people with CCA typically have an arm span that is greater than their height and very long fingers and toes </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Fetishism and can you explain it in depth? [/INST] A fetish (derived from the French fétiche, which comes from the Portuguese feitiço, and this in turn from Latin facticius, artificial and facere, to make) is an object believed to have supernatural powers, or in particular, a human-made object that has power over others. Essentially, fetishism is the attribution of inherent value, or powers, to an object.

Historiography
The term fetish has evolved from an idiom used to describe a type of object created in the interaction between European travelers and Africans in the early modern period to an analytical term that played a central role in the perception and study of non-Western art in general and African art in particular.
William Pietz, who, in 1994, conducted an extensive ethno-historical study of the fetish, argues that the term originated in the coast of West Africa during the sixteenth and seventeenth centuries. Pietz distinguishes between, on the one hand, actual African objects that may be called fetishes in Europe, together with the indigenous theories of them, and on the other hand, "fetish", an idea, and an idea of a kind of object, to which the term above applies.According to Pietz, the post-colonial concept of "fetish" emerged from the encounter between Europeans and Africans in a very specific historical context and in response to African material culture.
He begins his thesis with an introduction to the complex history of the word:

My argument, then, is that the fetish could originate only in conjunction with the emergent articulation of the ideology of the commodity form that defined itself within and against the social values and religious ideologies of two radically different types of noncapitalist society, as they encountered each other in an ongoing cross-cultural situation. This process is indicated in the history of the word itself as it developed from the late medieval Portuguese feitiço, to the sixteenth-century pidgin Fetisso on the African coast, to various northern European versions of the word via the 1602 text of the Dutchman Pieter de Marees... The fetish, then, not only originated from, but remains specific to, the problem of the social value of material objects as revealed in situations formed by the encounter of radically heterogeneous social systems, and a study of the history of the idea of the fetish may be guided by identifying those themes that persist throughout the various discourses and disciplines that have appropriated the term.
Stallybrass concludes that "Pietz shows that the fetish as a concept was elaborated to demonize the supposedly arbitrary attachment of West Africans to material objects. The European subject was constituted in opposition to a demonized fetishism, through the disavowal of the object."

History
Initially, the Portuguese developed the concept of the fetish to refer to the objects used in religious practices by West African natives. The contemporary Portuguese feitiço may refer to more neutral terms such as charm, enchantment, or abracadabra, or more potentially offensive terms such as juju, witchcraft, witchery, conjuration or bewitchment.
The concept was popularized in Europe circa 1757, when Charles de Brosses used it in comparing West African religion to the magical aspects of ancient Egyptian religion. Later, Auguste Comte employed the concept in his theory of the evolution of religion, wherein he posited fetishism as the earliest (most primitive) stage, followed by polytheism and monotheism. However, ethnography and anthropology would classify some artifacts of monotheistic religions as fetishes.
The eighteenth-century intellectuals who articulated the theory of fetishism encountered this notion in descriptions of "Guinea" contained in such popular voyage collections as Ramusios Viaggio e Navigazioni (1550), de Brys India Orientalis (1597), Purchass Hakluytus Posthumus (1625), Churchills Collection of Voyages and Travels (1732), Astleys A New General Collection of Voyages and Travels (1746), and Prevosts Histoire generale des voyages (1748).The theory of fetishism was articulated at the end of the eighteenth century by G. W. F. Hegel in Lectures on the Philosophy of History. According to Hegel, Africans were incapable of abstract thought, their ideas and actions were governed by impulse, and therefore a fetish object could be anything that then was arbitrarily imbued with imaginary powers.In the 19th and 20th centuries, Tylor and McLennan, historians of religion, held that the concept of fetishism fostered a shift of attention away from the relationship between people and God, to focus instead on a relationship between people and material objects, and that this, in turn, allowed for the establishment of false models of causality for natural events. This they saw as religious fetishism for Santa Claus on Christmas day and does not consider the birth of Jesus a central problem historically and sociologically.

Practice
The use of the concept in the study of religion derives from studies of traditional West African religious beliefs, as well as from Vodun, which in turn derives from those beliefs.
Fetishes were commonly used in some Native American religions and practices. For example, the bear represented the shaman, the buffalo was the provider, the mountain lion was the warrior, and the wolf was the pathfinder the cause of the war.

Japan
Kato Genchi cited jewelry, swords, mirrors, and scarves as examples of fetishism in Shintoism. Kato stated that leaving behind cities and going into rural areas, he could find many traces of animism, fetishism, and phallicism.Kato Genchi stated that the Ten Sacred Treasures were fetishes and the Imperial Regalia of Japan retained the same traits, and pointed out the similarities with the Pusaka of the natives of the East Indies and the Tjurunga of the Central Australians. The Kusanagi no Tsurugi was believed to provide supernatural protection (blessings) through the spiritual experience of the divine sword, and the Kusanagi no Tsurugi was deified and enshrined at Atsuta in Owari Province, which is now the Atsuta Shrine.Akaruhime no Kami, the deity of Hiyurikuso Shrine, was said to be a red ball. In the Kami era, the jewel around Izanagi-no-Mikotos neck was deified and called Mikuratana-kami.William George Aston remarked that the sword at Atsuta Shrine was originally an offering and later became a sacred object, as an example of Fetishism. Sword was one of mitama-shiro (spirit representative, spirit-token), or more commonly known as the shintai (god-body). He observed that people tends to think of the mitama (spirit) of a deity first as the seat of his real presence, and second as the deity itself </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is RAPADILINO syndrome and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is DSM-IV codes and can you explain it in depth? [/INST] DSM-IV codes are the classification found in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision, also known as DSM-IV-TR, a manual published by the American Psychiatric Association (APA) that includes almost all currently recognized mental health disorders.  The DSM-IV codes are thus used by mental health professionals to describe the features of a given mental disorder and indicate how the disorder can be distinguished from other, similar problems.The coding system utilized by the DSM-IV is designed to correspond with codes from the International Classification of Diseases, Ninth Revision, Clinical Modification, commonly referred to as the ICD-9-CM. Since early versions of the DSM did not correlate with ICD codes and updates of the publications for the ICD and the DSM are not simultaneous, some distinctions in the coding systems may still be present.  For this reason, it is recommended that users of these manuals consult the appropriate reference when accessing diagnostic codes
Note that NOS is an abbreviation for Not Otherwise Specified, indicating a cluster of symptoms that do not clearly fit in any single diagnostic category. NOS is often a provisional diagnosis pending additional information or testing.
For an alphabetical list, see DSM-IV codes (alphabetical).

Disorders usually first diagnosed in infancy, childhood, or adolescence
Mental retardation
317 Mild mental retardation
318.0 Moderate mental retardation
318.1 Severe mental retardation
318.2 Profound mental retardation
319 Mental retardation; severity unspecified

Learning disorders
315.00 Reading disorder
315.1 Mathematics disorder
315.2 Disorder of written expression
315.9 Learning disorder NOS

Motor skills disorders
315.4 Developmental coordination disorder

Communication disorders
315.31 Expressive language disorder
315.32 Mixed receptive-expressive language disorder
315.39 Phonological disorder
307.0 Stuttering
307.9 Communication disorder NOS

Pervasive developmental disorders
299.00 Autistic Disorder
299.80 Retts Disorder
299.10 Childhood Disintegrative Disorder
299.80 Asperger Syndrome
299.80 PDD-NOS

Attention-deficit and disruptive behavior disorders
Attention-Deficit Hyperactivity Disorder
314.01 Combined subtype
314.01 Predominantly hyperactive-impulsive subtype
314.00 Predominantly inattentive subtype
314.9 Attention-Deficit Hyperactivity Disorder NOS
Conduct disorder
312.81 Childhood onset
312.82 Adolescent onset
312.89 Unspecified onset
313.81 Oppositional Defiant Disorder
312.9 Disruptive Behavior Disorder NOS

Feeding and eating disorders of infancy or early childhood
307.52 Pica
307.53 Rumination disorder
307.59 Feeding disorder of infancy or early childhood

Tic disorders
307.23 Tourettes Disorder
307.22 Chronic motor or vocal tic disorder
307.21 Transient tic disorder
307.20 Tic disorder NOS

Elimination disorders
307.6 Enuresis (not due to a general medical condition)
307.7 Encopresis, without constipation and overflow incontinence
787.6 Encopresis, with constipation and overflow incontinence

Other disorders of infancy, childhood, or adolescence
309.21 Separation anxiety disorder
313.23 Selective mutism
313.89 Reactive attachment disorder of infancy or early childhood
307.3 Stereotypic movement disorder
313.9 Disorder of infancy, childhood, or adolescence NOSTop

Delirium, dementia, and amnestic and other cognitive disorders
Delirium
293.0 Delirium due to... [indicate the general medical condition]
780.09 Delirium NOS

Dementia
Dementia of the Alzheimers Type, with early onset
294.10 Without behavioral disturbance
294.11 With behavioral disturbance
Dementia of the Alzheimers Type, with late onset
294.10 Without behavioral disturbance
294.11 With behavioral disturbance
Vascular dementia
290.40 Uncomplicated
290.41 With delirium
290.42 With delusions
290.43 With depressed mood
Dementia due to HIV disease
294.10 Without behavioral disturbance
294.11 With behavioral disturbance
Dementia due to head trauma
294.10 Without behavioral disturbance
294.11 With behavioral disturbance
Dementia due to Parkinsons disease
294.10 Without behavioral disturbance
294.11 With behavioral disturbance
Dementia due to Huntingtons disease
294.10 Without behavioral disturbance
294.11 With behavioral disturbance
Dementia due to Picks disease
294.10 Without behavioral disturbance
294.11 With behavioral disturbance
Dementia due to Creutzfeldt–Jakob disease
294.10 Without behavioral disturbance
294.11 With behavioral disturbance
Dementia due to... [indicate other general medical condition]
294.10 Without behavioral disturbance
294.11 With behavioral disturbance
294.8 Dementia NOS

Amnestic disorders
294.0 Amnestic disorder due to... [indicate the general medical condition]
294.8 Amnestic disorder NOS

Other cognitive disorders
294.9 Cognitive disorder NOSTop

Mental disorders due to a general medical condition not elsewhere classified
293.89 Catatonic disorder due to... [indicate the general medical condition]
310.1 Personality change due to... [indicate the general medical condition]
(Subtypes: Labile, Disinhibited, Aggressive, Apathetic, Paranoid, Other, Combined, Unspecified)
293.9 Mental disorder NOS due to... [indicate the general medical condition]Top

Substance-related disorders
Alcohol-related disorders
Alcohol
305.00 Abuse
303.90 Dependence
291.89 -Induced anxiety disorder
291.89 -Induced mood disorder
291.1 -Induced persisting amnestic disorder
291.2 -Induced persisting dementia
291.5 -Induced psychotic disorder, with delusions
291.3 -Induced psychotic disorder, with hallucinations
291.89 -Induced sexual dysfunction
291.89 -Induced sleep disorder
303.00 Intoxication
291.0 Intoxication delirium
291.9 -Related disorder NOS
291.81 Withdrawal
291.0 Withdrawal delirium

Amphetamine (or amphetamine-like) related disorders
Amphetamine (or amphetamine-like)
305.70 Abuse
304.40 Dependence
292.89 -Induced anxiety disorder
292.84 -Induced mood disorder
292.11 -Induced psychotic disorder, with delusions
292.12 -Induced psychotic disorder, with hallucinations
292.89 -Induced sexual dysfunction
292.89 -Induced sleep disorder
292.89 Intoxication
292.81 Intoxication delirium
292.9 -Related disorder NOS
292.0 Withdrawal

Caffeine-related disorders
Caffeine
292.89 -Induced anxiety disorder
292.89 -Induced sleep disorder
305.90 Intoxication
292.9 -Related disorder NOS
293.9.10 consumption diversion

Cannabis-related disorders
Cannabis
305.20 Abuse
304.30 Dependence
292.89 -Induced anxiety disorder
292.11 -Induced psychotic disorder, with delusions
292.12 -Induced psychotic disorder, with hallucinations
292.89 Intoxication
292.81 Intoxication delirium
292.9 -Related disorder NOS

Cocaine-related disorders
Cocaine
305.60 Abuse
304.20 Dependence
292.89 -Induced anxiety disorder
292.84 -Induced mood disorder
292.11 -Induced psychotic disorder, with delusions
292.12 -Induced psychotic disorder, with hallucinations
292.89 -Induced sexual dysfunction
292.89 -Induced sleep disorder
292.89 Intoxication
292.81 Intoxication delirium
292.9 -Related disorder NOS
292.0 Withdrawal

Hallucinogen-related disorders
Hallucinogen
305.30 Abuse
304.50 Dependence
292.89 -Induced anxiety disorder
292.84 -Induced mood disorder
292.11 -Induced psychotic disorder, with delusions
292.12 -Induced psychotic disorder, with hallucinations
292.89 Intoxication
292.81 Intoxication delirium
292.89 -persisting perception disorder
292.9 -Related disorder NOS

Inhalant-related disorders
Inhalant
305.90 Abuse
304.60 Dependence
292.89 -Induced anxiety disorder
292.84 -Induced mood disorder
292.82 -Induced persisting dementia
292.11 -Induced psychotic disorder, with delusions
292.12 -Induced psychotic disorder, with hallucinations
292.89 Intoxication
292.81 Intoxication delirium
292.9 -Related disorder NOS

Nicotine-related disorders
Nicotine
305.1 Dependence
292.9 -Related disorder NOS
292.0 Withdrawal

Opioid-related disorders
Opioid
305.50 Abuse
304.00 Dependence
292.84 -Induced mood disorder
292.11 -Induced psychotic disorder, with delusions
292.12 -Induced psychotic disorder, with hallucinations
292.89 -Induced sexual dysfunction
292.89 -Induced sleep disorder
292.89 Intoxication
292.81 Intoxication delirium
292.9 -Related disorder NOS
292.0 Withdrawal

Phencyclidine (or phencyclidine-like) related disorders
Phencyclidine (or phencyclidine-like)
305.90 Abuse
304.60 Dependence
292.89 -Induced anxiety disorder
292.84 -Induced mood disorder
292.11 -Induced psychotic disorder, with delusions
292.12 -Induced psychotic disorder, with hallucinations
292.89 Intoxication
292.81 Intoxication delirium
292.9 -Related disorder NOS

Sedative-, hypnotic-, or anxiolytic-related disorders
Sedative, hypnotic, or anxiolytic
305.40 Abuse
304.10 Dependence
292.89 -Induced anxiety disorder
292.84 -Induced mood disorder
292.83 -Induced persisting amnestic disorder
292.82 -Induced persisting dementia
292.11 -Induced psychotic disorder, with delusions
292.12 -Induced psychotic disorder, with hallucinations
292.89 -Induced sexual dysfunction
292.89 -Induced sleep disorder
292.89 Intoxication
292.81 Intoxication delirium
292.9 -Related disorder NOS
292.0 Withdrawal
292.81 Withdrawal delirium

Polysubstance-related disorder
304.80 Polysubstance dependence

Other (or unknown) substance-related disorder
Other (or unknown) substance
305.90 Abuse
304.90 Dependence
292.89 -Induced anxiety disorder
292.81 -Induced delirium
292.84 -Induced mood disorder
292.83 -Induced persisting amnestic disorder
292.82 -Induced persisting dementia
292.11 -Induced psychotic disorder, with delusions
292.12 -Induced psychotic disorder, with hallucinations
292.89 -Induced sexual dysfunction
292.89 -Induced sleep disorder
292.89 Intoxication
292.9 -Related disorder NOS
292.0 Withdrawal
293.0 Delirium Due to ... [Indicate the General Medical Condition]Top

Schizophrenia and other psychotic disorders
Schizophrenia
295.20 Catatonic type
295.10 Disorganized type
295.30 Paranoid type
295.60 Residual type
295.90 Undifferentiated type
295.40 Schizophreniform disorder
295.70 Schizoaffective disorder
297.1 Delusional disorder
Erotomanic subtype
Grandiose subtype
Jealous subtype
Persecutory subtype
Somatic subtype
Mixed type
298.8 Brief psychotic disorder
297.3 Shared psychotic disorder
Psychotic disorder due to... [indicate the general medical condition]
293.81 With delusions
293.82 With hallucinations
298.9 Psychotic disorder NOSTop

Mood disorders
293.83 Mood Disorder Due to...[Indicate the General Medical Condition]
296.90 Mood Disorder NOS

Depressive disorders
300.4 Dysthymic disorder
Major depressive disorder
Major depressive disorder, recurrent
296.36 In full remission
296.35 In partial remission
296.31 Mild
296.32 Moderate
296.33 Severe without psychotic features
296.34 Severe with psychotic features
296.30 Unspecified
Major depressive disorder, single episode
296.26 In full remission
296.25 In partial remission
296.21 Mild
296.22 Moderate
296.23 Severe without psychotic features
296.24 Severe with psychotic features
296.20 Unspecified
311 Depressive disorder NOS

Bipolar disorders
Bipolar disorders
296.80 Bipolar disorder NOS
Bipolar I disorder, most recent episode depressed
296.56 In full remission
296.55 In partial remission
296.51 Mild
296.52 Moderate
296.53 Severe without psychotic features
296.54 Severe with psychotic features
296.50 Unspecified
296.40 Bipolar I disorder, most recent episode hypomanic
Bipolar I disorder, most recent episode manic
296.46 In full remission
296.45 In partial remission
296.41 Mild
296.42 Moderate
296.43 Severe without psychotic features
296.44 Severe with psychotic features
296.40 Unspecified
Bipolar I disorder, most recent episode mixed
296.66 In full remission
296.65 In partial remission
296.61 Mild
296.62 Moderate
296.63 Severe without psychotic features
296.64 Severe with psychotic features
296.60 Unspecified
296.7 Bipolar I disorder, most recent episode unspecified
Bipolar I disorder, single manic episode
296.06 In full remission
296.05 In partial remission
296.01 Mild
296.02 Moderate
296.03 Severe without psychotic features
296.04 Severe with psychotic features
296.00 Unspecified
296.89 Bipolar II disorder
301.13 Cyclothymic disorder
293.83 Mood disorder due to... [indicate the general medical condition]
296.90 Mood disorder NOSTop

Anxiety disorders
300.02 Generalized anxiety disorder
Panic disorder
300.21 With agoraphobia
300.01 Without agoraphobia
300.22 Agoraphobia without history of panic disorder
300.29 Specific phobia
300.23 Social phobia
300.3 Obsessive-compulsive disorder
309.81 Posttraumatic stress disorder
308.3 Acute stress disorder
293.84 Anxiety disorder due to a general medical condition
293.89 Anxiety disorder due to... [indicate the general medical condition]
300.00 Anxiety disorder NOSTop

Somatoform disorders
300.81 Somatization disorder
300.82 Undifferentiated somatoform disorder
300.11 Conversion disorder
Pain disorder
307.89 Associated with both psychological factors and a general medical condition
307.80 Associated with psychological factors
300.7 Hypochondriasis/Illness anxiety disorder
300.7 Body dysmorphic disorder
300.82 Somatoform disorder NOSTop

Factitious disorders
Factitious disorder
300.19 With combined psychological and physical signs and symptoms
300.19 With predominantly physical signs and symptoms
300.16 With predominantly psychological signs and symptoms
300.19 Factitious disorder NOSTop

Dissociative disorders
300.6 Depersonalization disorder
300.12 Dissociative amnesia
300.14 Dissociative identity disorder
300.15 Dissociative disorder not otherwise specified

Sexual and gender identity disorders
Sexual dysfunctions
625.8 Female hypoactive sexual desire disorder due to.. </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Iniencephaly and can you explain it in depth? [/INST] Iniencephaly is a rare type of cephalic disorder characterised by three common characteristics: a defect to the occipital bone, spina bifida of the cervical vertebrae and retroflexion (backward bending) of the head on the cervical spine. Stillbirth is the most common outcome, with a few rare examples of live birth, after which death almost invariably occurs within a short time.
The disorder was first described by Étienne Geoffroy Saint-Hilaire in 1836. The name is derived from the Ancient Greek word ἰνίον inion, for the occipital bone/nape of the neck.

Classifications
There are two types of iniencephaly. The more severe group is iniencephaly apertus (open iniencephaly), involving the development of an encephalocele. In the other group, iniencephaly clausus (closed iniencephaly), the encephalocele is absent.

Signs and symptoms
The affected infant tends to be short, with a disproportionately large head. The fetal head of infants born with iniencephaly are hyperextended while the foramen magnum is enlarged and opens through the widened pedicles. The defective neural arches directly into the upper cervical reach of the spinal canal, causing the formation of a common cavity between most of the spinal cord and the brain. The skin of the anterior chest is connected directly to the face, bypassing the formation of a neck, while the scalp is directly connected to the skin of the back. Because of this, those born with this anomaly either have a highly shortened neck or no neck at all. This causes extreme retroflexion, or backward bending, of the head in a "star-gazing" fashion. The spine is severely distorted as well along with significant shortening due to marked lordosis. The vertebrae, especially cervical, are fused together in abnormal shapes and their numbers are reduced. The spinal cord is almost always defective while the ventricular system is often dilated and the cortex is thinned. Sometimes, in the case of iniencephaly apertus, an encephalocele (sac-like protrusions of the brain through an opening in the cranium) forms.

Additional symptoms
Additional symptoms include:

Causes
Though the iniencephaly is not genetic with its cause unknown, studies have shown that there are certain factors that can increase the risk of mothers giving birth to children with these anomalies.

Chromosomal abnormalities
Abnormalities in chromosomes such as trisomy 18, trisomy 13, and monosomy X have been shown to be tied to this disorder.

Environmental factors
Mothers with poor socioeconomic conditions, poor nutrition, low parity, and lack of folic acid supplementation, and/or hyperhomocysteinemia have shown to be at larger risk.

Drugs
Animal studies have shown that administration of the drugs vinblastine, streptonigrin, triparano, sulfonamide, tetracycline, antihistamines, and antitumor agents to pregnant mothers have resulted in offspring born with iniencephaly. The drug clomiphene, a drug commonly used for ovulation stimulation in fertility treatments, has also been seen to be associated with iniencephaly.

Obesity
Studies have shown that obesity of the mother increases the risk of neural tube disorders such as iniencephaly by 1.7 fold while severe obesity increases the risk by over 3 fold.

History of iniencephaly
Once a mother has given birth to a child with iniencephaly, risk of reoccurrence increases to 1-5%.

Pathogenesis
The exact pathogenesis of iniencephaly is still unknown though there are proposed theories, most of which view the neural tube malformation from the primary neural anomaly standpoint.
Marin-Padilla and MarinPadilla have proposed that the cause for the abnormalities has to do with a deficiency in the primary mesoderm. P. Erdinçler, et al. suggests from their findings that the cause of the anomaly is actually a defect in the occipital bone and rachischisis of the posterior vertebral arches leading to herniation of neural tissue through the opening in the bone during gestation.

Diagnosis
The most accurate method of diagnosis is prenatal screening through real-time fetal images </s>