<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 Floating–Harbor syndrome and can you explain it in depth? [/INST] Floating–Harbor syndrome, also known as Pelletier–Leisti syndrome, is a rare disease with fewer than 50 cases described in the literature. It is usually diagnosed in early childhood and is characterized by the triad of proportionate short stature with delayed bone age, characteristic facial appearance, and delayed speech development. Although its cause is unknown, it is thought to result from genetic mutation, and diagnosis is established by the presence of a heterozygous SRCAP mutation in those with clinical findings of FHS.

Signs and symptoms
Below are the common clinical features of those diagnosed with Floating–Harbor syndrome. Patients will show varying degrees of some or all FHS symptoms. Facial abnormalities  are the most defining aspects of those diagnosed with this disease.

Cardinal facial features
Triangular face
Deep-set eyes
Short philtrum
Wide mouth with a thin vermilion border of the upper lip
Long nose with a narrow bridge and broad, bulbous base
Low-set ears

Voice quality and language
Dysarthria and verbal dyspraxia with phoneme imprecision
Hypernasality
High-pitched voices
Severe receptive and expressive language impairment across all domains of function

Bodily features
Significant delay in bone age (-2 SD or greater) with normalization between 6–12 years old
Skeletal anomalies: brachydactyly, broad fingertips or clubbing, clinodactyly, short thumbs, prominent joints, clavicle abnormalities
Short adult stature: for females, maximum height was at the 20th percentile; for males, the maximum height was at the 25th percentile, though male height varied more widelyThe differential diagnosis of broad thumbs includes Rubinstein-taybi syndrome, where they are a cardinal feature. FHS is also in the differential, which logically agrees with the thought that the disease is a result of a mutation in SRCAP, as this gene interacts with CBP.

Behavior
Tantrums during infancy
Attention deficit-hyperactivity disorder (ADHD) during school years: impulsivity, inattention, restlessness
Unpredictable, aggressive outbursts
Autistic spectrum disorder (one case)
Asperger syndrome (one case)
Obsessive compulsive disorder (two cases)

Other observations
Intellectual disability: in all cases each individual showed a varying degree of intellectual impairment and learning disability, ranging from borderline normal to moderate intellectual disability
Early entry into puberty is shown in some girls, leading to menorrhagia and irregular periods
Dental problems (caries, malocclusion, dysplastic, small teeth)
Visual impairment

Mechanism
The cause of this condition is unknown but evidence of familial inheritance and sporadic genetic mutation has been linked to cases of FHS. Two possibly familial cases have been reported—one in a mother and son, and the other in a mother and daughter. This suggests an autosomal dominant inheritance but additional cases need to be investigated to establish this. Another report has suggested that the inheritance may be autosomal recessive. In all of these cases, however, the mothers and children were not similarly affected, suggesting a variable clinical expression of the syndrome.In a study published by the American Journal of Human Genetics in 2012, exome sequencing was used to investigate a group of unrelated individuals with classic features of FHS and identified heterozygous mutations in SRCAP as causative of this disorder.  Each reported mutation was truncating (nonsense or frameshift) and occurred between codons 2,407 and 2,517 in exon 34, resulting in the loss of three C-terminal AT-hook motifs. SRCAP encodes a SNF2-related chromatin-remodeling ATPase that is a coactivator for CREB-binding protein (or CBP), which is the major cause of Rubinstein–Taybi syndrome. This disrupted interaction between the proteins most likely explains the clinical overlap between FHS and RTS.
SRCAP has been shown to transduce signals of nuclear (steroid) hormone receptors and Notch pathways, showing that it plays diverse roles in gene expression.
SRCAP contains several functional domains (SNF2 like ATPase, an N-terminal HSA domain, and three C-terminal AT-hook DNA-binding motifs).
The CBP interaction domain of SRCAP is located centrally.Thus, the mechanism of disease in FHS is suspected to be dominant-negative (or antimorphic) due to the mutation in the final exon that results in the loss of the major transactivation function of SRCAP (or loss of one or more critical domains). All of the patients that carried the mutation also had obvious physical symptoms (i.e., prominent nose, delayed bone age, and short stature). Those who tested negative for the mutation often had dysmorphic facial features distinct from classical FHS, as well as a formal diagnosis of autism.

Drawbacks to findings
From the same group, three individuals whose phenotype most closely resembled FHS carried no mutation on the SRCAP gene. Though these findings are a large step in determining the underlying cause of FHS and widely accepted, others would claim molecular diagnosis is not always successful and the mutation is not a mandatory feature for the diagnosis of FHS.

Diagnosis
Until recently, doctors have diagnosed patients with FHS based on clinical observations and how well they fit the disease description, usually occurring in early childhood. Molecular genetic testing is also used now to test for genetic mutations. By performing a sequence analysis test of select exons, mutations can be detected in exon 34 of the SRCAP gene. This mutation has been observed in 19 patients to date.
In most cases, if the patient shows classic facial features of FHS, the molecular testing will show a mutation on the SRCAP gene.

Differential diagnosis
FHS shares some common features with Rubinstein–Taybi (due to overlapping effects of mutations on SRCAP), however cranial and hand anomalies are distinctive: broad thumbs, narrow palate, and microcephaly are absent in Floating-Harbor Syndrome. One child in the UK has a diagnosis of microcephaly alongside Floating–Harbor syndrome.

Management
There are no cures for FHS. Close monitoring of growth in the first few years is essential, as well as annual general health screening and tests listed below. An FHS diagnosis will affect the individual and those there to support them.Managing symptoms and features of FHS involves maintaining a close watch on the patients physical as well as mental health. This would include:
Sequencing of SRCAP exons 31–34 in all suspected cases
Complete assessments of auditory and visual systems
Renal and urinary tract ultrasound
Orthopedic assessment of hip dysplasia and clavicle abnormalities
Neurologic assessment if there is a suspicion of seizures
Dental hygiene to prevent cavities and to monitor for malocclusion
Evaluation for growth hormone deficiency at baseline, to be repeated if loss of growth velocity occurs
Monitoring of bone age and pubertal timing in case of precocious puberty
Psychoeducational assessments corrected for deficiencies in expressive language and sensory issues
Monitoring of behavioral disturbances and provision of early intervention
Counseling for families regarding recurrence risk and the offspring of individuals with FHSSpecial education programs and vocational training to address developmental disabilities are highly recommended, as well as communication rehabilitation with sign language or alternative means of communication. Behavior management strategies could also include referrals to behavior specialists or psychologists for help. For those concerned, genetic counseling can be sought for issues related to testing of at-risk relatives.

History
The first identified instances occurred in 1973 at the Boston Floating Hospital, and in 1975 at Harbor General Hospital in Torrance, California </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 Recurrent miscarriage and can you explain it in depth? [/INST] Recurrent miscarriage is three or more consecutive pregnancy losses. In contrast, infertility is the inability to conceive. In many cases the cause of RPL is unknown. After three or more losses, a thorough evaluation is recommended by American Society of Reproductive Medicine. About 1% of couples trying to have children are affected by recurrent miscarriage.

Causes
There are various causes for recurrent miscarriage, and some can be treated. Some couples never have a cause identified, often after extensive investigations. About 50–75% of cases of recurrent miscarriage are unexplained.

Chromosomal disorders
A balanced translocation or Robertsonian translocation in one of the partners leads to unviable fetuses that are miscarried. This explains why a karyogram is often performed in both partners if a woman has experienced repeated miscarriages.Aneuploidy may be a cause of a random spontaneous as well as recurrent pregnancy loss. Aneuploidy is more common with advanced reproductive age reflecting decreased germ cell quality.Larger chromosomal disorders are generally detected on karyotype. In couples where a miscarried embryo has an abnormal karyotype, 76% of subsequent miscarried embryos have shown abnormal karyotypes as well. On the other hand, this group of couples have a better long-term live birth rate than those where miscarried embryos have normal karyotype.

Lifestyle factors
While lifestyle factors have been associated with increased risk for miscarriage in general, and are usually not listed as specific causes for RPL, every effort should be made to address these issues  in patients with RPL. Of specific concern are chronic exposures to toxins including smoking, alcohol, and drugs.

Anatomical conditions
Fifteen percent of women who have experienced three or more recurring miscarriages have some anatomical reason for the inability to complete the pregnancy. The structure of the uterus has an effect on the ability to carry a child to term. Anatomical differences are common and can be congenital.

Cervical conditions
In the second trimester a weak cervix can become a recurrent problem. Such cervical incompetence leads to premature pregnancy loss resulting in miscarriages or preterm deliveries. It has been estimated that cervical insufficiency is a cause in about 8% of women with second trimester recurrent miscarriages.

Endocrine disorders
Women with hypothyroidism are at increased risk for pregnancy losses. Unrecognized or poorly treated diabetes mellitus leads to increased miscarriages. Women with polycystic ovary syndrome also have higher loss rates possibly related to hyperinsulinemia or excess androgens. Inadequate production of progesterone in the luteal phase may set the stage for RPL (see below).

Thrombophilia
An important example is the possible increased risk of miscarriage in women with thrombophilia (propensity for blood clots). The most common problem is the factor V Leiden and prothrombin G20210A mutation. Some preliminary studies suggest that anticoagulant medication may improve the chances of carrying pregnancy to term but these studies need to be confirmed before they are adopted in clinical practice. Note that many women with thrombophilia go through one or more pregnancies with no difficulties, while others may have pregnancy complications. Thrombophilia may explain up to 49–65% of recurrent miscarriages.

Immune factors
A common feature of immune factors in causing recurrent pregnancy loss appears to be a decreased maternal immune tolerance towards the fetus.

Antiphospholipid syndrome
The antiphospholipid syndrome is an autoimmune disease that is a common cause of recurrent pregnancy loss. Around 15% of the women who have recurrent miscarriages have high levels of antiphospholipid antibodies. Women who have had more than one miscarriage in the first trimester, or a miscarriage in the second trimester, may have their blood tested for antibodies, to determine if they have antiphospholipid syndrome. Women diagnosed with antiphospholipid syndrome generally take aspirin or heparin in subsequent pregnancies, but questions remain due to the lack of high quality trials.

Thyroid antibodies
Anti-thyroid autoantibodies are associated with an increased risk of recurrent miscarriage with an odds ratio of 2.3 with a 95% confidence interval of 1.5–3.5.

Increased uterine NK cells
Natural killer cells, a type of white blood cell, are present in uterine tissue. High levels of these cells may be linked to RPL but high numbers or the presence of these cells is not a predictor of pregnancy loss in women who have not have had a miscarriage.

Parental HLA sharing
Earlier studies that perhaps paternal sharing of HLA genes would be associated with increased pregnancy loss have not been confirmed.

Male-specific minor histocompatibility
Immunization of mothers against male-specific minor histocompatibility (H-Y) antigens has a pathogenic role in many cases of secondary recurrent miscarriage, that is, recurrent miscarriage in pregnancies succeeding a previous live birth. An example of this effect is that the male:female ratio of children born prior and subsequent to secondary recurrent miscarriage is 1.49 and 0.76 respectively.

Ovarian factors
Luteal phase defect
The issue of a luteal phase defect is complex. The theory behind the concept suggests that an inadequate amount of progesterone is produced by the corpus luteum to maintain the early pregnancy. Assessment of this situation was traditionally carried out by an endometrial biopsy, however recent studies have not confirmed that such assessment is valid. Studies about the value of progesterone supplementation remain deficient, however, such supplementation is commonly carried out on an empirical basis.

Infection
Infections are estimated to be responsible for between 0.5 and 5% of cases with recurrent miscarriage. The main suspected pathogens are mycoplasma, ureaplasma, Chlamydia trachomatis, Listeria monocytogenes, and herpes simplex virus. An infectious evaluation may be warranted in people with immunodeficiency, or with signs of chronic endometritis/cervicitis on examination. Otherwise, there is no evidence that routine infectious evaluation is appropriate or productive.Chronic endometritis (CE) due to common bacteria has been found to be prevalent in some women with a history of recurrent miscarriage. One study found that 71 percent of women who tested positive for this condition were successfully treated by an antibiogram-based antibiotic treatment. 78.4 percent of these women subsequently became pregnant in the year following treatment. The study concludes that "CE is frequent in women with recurrent miscarriages," and that "antibiotic treatment seems to be associated with an improved reproductive outcome." The authors also conclude, "that hysteroscopy should be a part of the diagnostic workup of infertile women complaining of unexplained recurrent miscarriage." Despite challenges in diagnosing chronic endometritis, often done by identifying plasma cells within the lining of the womb, a recent study identified women with chronic endometritis were more likely to have a miscarriage than women without.

Assessment
Transvaginal ultrasonography has become the primary method of assessment of the health of an early pregnancy.
In non-pregnant patients who are evaluated for recurrent pregnancy loss the following tests are usually performed.
Parental chromosome testing (karyogram) is generally recommended after 2 or 3 pregnancy losses. Blood tests for thrombophilia, ovarian function, thyroid function and diabetes are performed.

Treatment
If the likely cause of recurrent pregnancy loss can be determined treatment is to be directed accordingly. In pregnant women with a history of recurrent miscarriage, anticoagulants seem to increase the live birth rate among those with antiphospholipid syndrome and perhaps those with congenital thrombophilia but not in those with unexplained recurrent miscarriage. One study found that in many women with chronic endometritis, "fertility was restored after appropriate antibiotic treatment."There are currently no treatments for women with unexplained recurrent pregnancy loss. The majority of patients are counseled to try to conceive again, and chances are about 60% that the next pregnancy is successful without treatment. However, each additional loss worsens the prognostic for a successful pregnancy and increases the psychological and physical risks to the mother. Aspirin has no effect in preventing recurrent miscarriage in women with unexplained recurrent pregnancy loss. Immunotherapy has not been found to help </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 Dandy–Walker malformation and can you explain it in depth? [/INST] Dandy–Walker malformation (DWM), also known as Dandy–Walker syndrome (DWS), is a rare congenital brain malformation in which the part joining the two hemispheres of the cerebellum (the cerebellar vermis) does not fully form, and the fourth ventricle and space behind the cerebellum (the posterior fossa) are enlarged with cerebrospinal fluid. Most of those affected develop hydrocephalus within the first year of life, which can present as increasing head size, vomiting, excessive sleepiness, irritability, downward deviation of the eyes and seizures. Other, less common symptoms are generally associated with comorbid genetic conditions and can include congenital heart defects, eye abnormalities, intellectual disability, congenital tumours, other brain defects such as agenesis of the corpus callosum, skeletal abnormalities, an occipital encephalocele or underdeveloped genitalia or kidneys. It is sometimes discovered in adolescents or adults due to mental health problems.DWM is usually caused by a ciliopathic or chromosomal genetic condition, though the causative condition is only identified in around half of those diagnosed before birth and a third of those diagnosed after birth. The mechanism involves impaired cell migration and division affecting the long period of development of the cerebellar vermis. The mechanism by which hydrocephalus occurs in DWM is not yet fully understood. The condition is diagnosed by MRI or, less commonly, prenatal ultrasound. There are other malformations that can strongly resemble DWM, and disagreement exists around the criteria and classifications used for the malformation.Treatment for most involves the implantation of a cerebral shunt in infancy. This is usually inserted in the posterior fossa, but a shunt in the lateral ventricles may be used instead or in conjunction. Endoscopic third ventriculostomy (ETV) is a less invasive option for patients older than 1 year. Posterior fossa shunts are most effective (80% of the time) but carry the highest risk of complications, while ETV is least effective but has the least risk of complications. The mortality rate is roughly 15%, mostly due to complications from hydrocephalus or its treatment, which can include subdural haematomas or infection. The prognosis after successful hydrocephalus treatment is usually good but depends on any associated condition and its symptoms. Those without hydrocephalus are treated based on any associated symptoms or condition.The prevalence of DWM is estimated at between 1 in 25,000 to 1 in 50,000. DWM is the cause of around 4.3% of cases of congenital hydrocephalus and 2.5% of all cases of hydrocephalus. At least 21% of those with DWM have a sibling with the malformation, and at least 16% have a parent with the malformation. The malformation was first described by English surgeon John Bland-Sutton in 1887, though it was named by German psychiatrist Clemens Ernst Benda in 1954 after American neurosurgeons Walter Dandy and Arthur Earl Walker, who described it in 1914 and 1942, respectively.

Signs and symptoms
Hydrocephalus
The most frequent and prominent symptoms of DWM are those associated with hydrocephalus in the postnatal period. Hydrocephalus occurs in an estimated 80% of patients with classic DWM. This usually presents within the first year of life (85% of the time), most often within the first 3 months. Signs of hydrocephalus in infants include increasing head size, vomiting, excessive sleepiness, irritability, downward deviation of the eyes (known as "sunsetting eyes") and seizures. In contrast to classic DWM, only around 30% of those with Dandy–Walker variant (DWV), in which the posterior fossa is not enlarged, have hydrocephalus.

Neurological
Despite the hypoplastic cerebellar vermis, just over half of individuals with DWM (between 27% and 84%) do not appear to have significant intellectual disability or developmental delay. However, many of the genetic conditions associated with DWM can present with developmental delay and other brain anomalies. Agenesis of the corpus callosum has been found in between 5% and 17% of those with DWM. This does not seem to result in intellectual disability on its own, however. Other brain abnormalities known to be sometimes associated with DWM include grey matter heterotopia, pachygyria (fewer ridges in the brain), lissencephaly (shallower ridges), polymicrogyria, holoprosencephaly and schizencephaly. Individuals with these features tend to have developmental delay or seizures. Those without any other central nervous system abnormalities tend to have normal or close-to-normal intellectual development. A 2003 review found that moderate-to-severe intellectual disability and non-DWM brain abnormalities were only present in those with the most severe cerebellar vermis malformations (less than two fissures/three lobules in the vermis), and these comprised 16% of their sample. Hydrocephalus also affected all of these patients.In Dandy–Walker variant (DWV) and mega cisterna magna specifically, which are less severe malformations, there appears to be an increased rate of psychotic spectrum disorders such as schizophrenia, bipolar disorder, mania or catatonia.

Associated anomalies
A 2017 review found the following associations in patients with DWS (usually from an associated genetic condition or abnormality):
27% of patients had a congenital heart defect. These included patent ductus arteriosus, coarctation of the aorta, ventricular septal defect and atrial septal defect. In 2.7% of patients, heart failure was reported.
24% of patients had at least one ocular abnormality. These included cataracts, small eyes (microphthalmia), chorioretinal dysplasia/atrophy, optic nerve dysplasia/atrophy, a small cornea (microcornea) or corneal opacity (leukoma), short-sightedness (myopia) and coloboma (a hole in an eye structure).
16% of patients were diagnosed with a mental or behavioural disorder, with 6.4% also having a learning disability. 5.3% had either bipolar disorder or a psychotic spectrum disorder, and 2.1% had ADHD. Slightly more of these were found in Dandy–Walker variant (DWV) than in classic DWM, despite DWV being less common, at only around 20% of DWS diagnoses.
Around 12% of patients had cancers or tumours arising from congenital genetic abnormalities. The most common were neurocutaneous melanosis (5.9%), hemangiomas (4.8%, including those with PHACE syndrome) and Wilms tumour (4.4%). 3.2% of patients had congenital melanocytic nevi, and 2.1% had tongue hamartoma. The melanocytic tumours in these cases are thought to relate to the same genetic errors in the development of the embryonic neural tube that lead to the DWM, since the subsequent embryonic neural crest gives rise to melanocytes, among other cells.
10% of patients had endocrine or metabolic disorders, and 2.7% had excessive hair growth (hypertrichosis).
9% of patients (almost all with classic DWM) had musculoskeletal abnormalities, which included scoliosis or kyphoscoliosis and arthrogryposis.
5.9% of patients had underdeveloped reproductive organs, such as hypoplastic genitalia or undescended testicles (cryptorchidism).
5.3% of patients had underdeveloped or polycystic kidneys.Occipital encephalocele may occur in DWM. This has generally been found at rates between 6 and 8%. It has been suggested to occur to compensate for the increased pressure in the posterior fossa during foetal life.Syringomyelia occasionally occurs with DWM, though it is not certain how often. One review reported an occurrence of 4.3% in a sample. This may be due to herniation of the bottom of the cyst through the foramen magnum (a similar mechanism to Chiari malformation). Alternatively, it may be a result of hydrocephalus, in which it forms as a "fifth ventricle" due to an enlarged central canal.Rarely, spina bifida has been found with DWM. When it is present, it is usually spina bifida occulta.

Cause
DWM is caused by any disruption to embryonic development that affects the formation of the cerebellar vermis. This is usually a genetic mutation that results in impaired cell migration and division. A large number of genetic conditions can result in the anomaly. In a large portion of DWM cases, the condition is identified in the person affected, however in most cases the cause is not identified. At least 21% of those with DWM have a sibling with the malformation, and at least 16% have a parent with the malformation.

Ciliopathic genetic conditions
A genetic condition is identified in around 33% of those diagnosed with DWM after birth. In a 2017 review, 4.3% were found to have PHACE syndrome, a condition involving brain, cardiovascular and eye abnormalities, while 2.3% had Joubert syndrome, a condition involving neurological and sometimes eye and kidney abnormalities. Anywhere from 21% to 81% of those with PHACE syndrome have DWM. Other comorbid genetic conditions that were found included oculocerebrocutaneous syndrome, oral-facial-digital syndrome, Coffin–Siris syndrome, Meckel–Gruber syndrome type 7 and Kallmann syndrome, among many others. DWM has also been associated with 3C syndrome, Rubinstein–Taybi syndrome, Marden–Walker syndrome, Sheldon–Hall syndrome, Shah–Waardenburg syndrome, Fryns syndrome,< Walker–Warburg syndrome, Fukuyama congenital muscular dystrophy, Ellis–van Creveld syndrome, Fraser syndrome, Aicardi syndrome, Cornelia de Lange syndrome,< Klippel–Feil syndrome and acrocallosal syndrome, among others. Many of these disorders are classified as ciliopathies, genetic disorders that affect the cellular primary cilia, thin cell projections made from microtubules that are believed to be crucial in signalling embryonic cell division and migration. DWM is one of the single largest predictors of a ciliopathic genetic disease.Other genes that have been linked to DWM include ZIC1, ZIC4, FOXC1, FGF17, LAMC1 and NID1.

Chromosomal abnormalities
In those who are diagnosed with DWM before birth on ultrasound, up to half are found to have a chromosomal abnormality, with the most common being Edwards syndrome (trisomy 18), at roughly 26% of prenatal DWM cases. 6.5% of those diagnosed with DWM after birth also have Edwards syndrome. Other chromosomal abnormalities that can lead to DWM include triploidy, Patau syndrome (trisomy 13), trisomy 9 and partial 3q deletion or duplication. The 3q24 region contains the ZIC1 and ZIC4 genes, known to be associated with DWM.

External toxins
Warfarin use during pregnancy has been known to lead to systemic defects in the fetus, including ocular dysgenesis, microcephaly, agenesis of the corpus callosum, skeletal abnormalities and heart defects. In 1985, it was also linked to DWM.

Pathophysiology
The cerebellum begins forming at the fifth week of embryonic development. It differentiates at the top of the metencephalon, while the pons (in the brainstem) differentiates at the bottom, separated by the fourth ventricle. The cerebellar hemispheres form from the rhombic lips on the forward surface of the fourth ventricle, which expand and roll over to fuse in the midline to form the cerebellar vermis by the 15th week. If this process does not complete, the cerebellar vermis will not form fully. This long period of development of the cerebellar vermis makes it particularly vulnerable to disruptions.In DWM, the fourth ventricle opens up into and is continuous with almost the entire posterior fossa subarachnoid space.

Pathophysiology of hydrocephalus
The reason why hydrocephalus occurs in DWM is not yet fully understood. The earliest authors had put it down it to blockage or narrowing of the foramina of Magendie and Luschka, the two apertures in the fourth ventricle that allow cerebrospinal fluid (CSF) to escape into the subarachnoid space of the posterior fossa. However, later studies found that these foramina are usually open in DWM. Hydrocephalus is also usually (80% of the time) not present at birth in those with DWM.The impairment to CSF flow may lie beyond the outlets of the fourth ventricle. Theories of abnormal development or inflammation of the arachnoid mater in the posterior fossa have been put forward. The arachnoid mater contains granulations necessary to return CSF from the subarachnoid spaces to the dural veins and circulation. Excisions of the cyst in DWM have not been able to show whether impaired arachnoid absorption is involved, since the subarachnoid space always takes days to weeks to fill up following excision.Aqueductal stenosis (narrowing of the passage between the third and fourth ventricles) does not seem to be a factor in DWM. It is usually open, and shunts placed in the posterior fossa cyst almost always drain all above ventricles. When it is present, it may be the result of compression from a herniated vermis or cyst or an associated developmental abnormality.It is known that once hydrocephalus has started, the compression by the posterior fossa cyst against the venous passages in the arachnoid mater is involved in the worsening pathology.

Diagnosis
Dandy–Walker malformation is diagnosed based on the characteristic neuroimaging findings. It can be diagnosed prenatally on ultrasound as early as 14 weeks of gestation, although it is usually diagnosed postnatally by MRI. It is diagnosed within the first year of life 41% of the time, normally due to increasing signs of hydrocephalus, but 28% of the time it is discovered in adolescence or adulthood due to mental health problems, such as psychosis or mood disorder.

Criteria and classification
The precise diagnostic criteria and classification systems of DWM are not agreed upon, and significant dispute exists as to which terms or criteria should be used. The core criteria of DWM are hypoplasia of the cerebellar vermis and an enlarged fourth ventricle and posterior fossa (the space behind the cerebellum), though the specific degree of hypoplasia or cystic enlargement for diagnosis of DWM is not agreed upon. Additionally, there are several similar conditions which have at various times been grouped with DWM on a continuum by some authors and separated as distinct by others, further complicating diagnosis.In 1976, Harwood-Nash and Fitz proposed the term Dandy–Walker variant (DWV) for a malformation in which the posterior fossa is not enlarged but the cerebellar vermis is hypoplastic. In 1989, Barkovich et al. proposed the term Dandy–Walker complex (DWC) to include classic DWM and DWV (under type A) plus a third malformation (under type B) in which the cerebellar vermis remains large enough to sit between the fourth ventricle and the cisterna magna beneath it, and instead it is mostly the cisterna magna that is enlarged. In this type, the hypoplasia of the cerebellar vermis does not reach past the horizontal midline of the fourth ventricle, and the posterior fossa is also not as large. The authors noted that this form would previously have been classified as simply mega–cisterna magna. In 1999, Calabró et al. first used the phrase Dandy–Walker continuum when referring to proposals that a condition known as Blakes pouch cyst falls under the umbrella of the Dandy–Walker complex proposed by Barkovich. Later authors would put these terms and systems under intense scrutiny and state that they added considerable confusion to the diagnosis of DWM. However, they remain commonly used.In 2011, Spennato et al. came up with a set of criteria based on Klein et al. (2003) that they considered necessary for diagnosis of DWM:
The lower portion of the cerebellar vermis is absent to varying degrees (three quarters, one half or one quarter missing).
The posterior fossa (the space behind the cerebellum) is enlarged, and its cerebrospinal fluid flow is continuous with that of the fourth ventricle.
The rest of the cerebellar vermis is hypoplastic and is pushed upwards and rotated forwards due to the enlarged posterior fossa.
The cerebellar hemispheres are pushed forwards and to the side by the enlarged posterior fossa.
The angle at the centre of the cerebellar vermis (representing the location of the fastigial nucleus) is large, giving a flattened appearance to the bottom of the vermis, or the fastigial nucleus is absent entirely.
The confluence of sinuses, part of the drainage system located at the far rear of the occipital lobe, is elevated due to the enlarged posterior fossa. (The adjacent cerebellar tentorium is also elevated.)Due to the inconsistency of the presence of hydrocephalus in DWM, Spennato and Klein suggested that it should not be considered a criterion for DWM. Kleins criteria differed from Spennatos mainly in that it required no apparent cerebellar hemisphere hypoplasia, but it may also have required the vermis to touch the tentorium or an absence of brainstem abnormalities.

Methods
DWM can be observed prenatally on ultrasound as early as 14 weeks of gestation, though an MRI scan is the most useful method for diagnosis. MRI can delineate the shape and extent of the malformation as well as assessing additional areas for malformations such as the cerebellar hemispheres, cerebral aqueduct or corpus callosum. Cardiac-gated phase-contrast MRI can observe the flow of cerebrospinal fluid (CSF) during systole and diastole of the heart. In true DWM, this will find a flow from the cerebral aqueduct to the posterior fossa and no flow between the cisterna magna and the space behind the cervical spinal cord.CT may also be used if MRI is unavailable, but it provides less detail. Klein et al. (2003) suggested that a suspected diagnosis based on CT or ultrasound should not be confirmed until an MRI is performed, due to the large number of conditions that can present highly similarly and confound diagnosis.

Differential diagnosis
DWM has a large number of conditions that can present highly similarly on imaging and confound diagnosis.

Blakes pouch cyst
Blakes pouch cyst (BPC), or persistent Blakes pouch, is a condition that arises when Blakes pouch, an invagination in the fourth ventricle that ruptures at around 4 months of gestation to form the foramen of Magendie (medial aperture), fails to rupture. This can lead to a dilated fourth ventricle and subsequent hydrocephalus of all four ventricles.In a Blakes pouch cyst, unlike in DWM:
The cerebellum is not hypoplastic, though it may be compressed by the enlarged posterior fossa (mass effect).
The posterior fossa is not enlarged.
The cerebellar tentorium/confluence of sinuses is not raised.
Hydrocephalus, when it occurs, involves all four ventricles.Some authors, however, consider Blakes pouch cyst part of a continuum with DWM (the "Dandy–Walker continuum").

Mega cisterna magna
Mega cisterna magna is a condition in which the cisterna magna, the subarachnoid cistern below the fourth ventricle, is enlarged. It has been proposed to be due to a delayed rupture of Blakes pouch rather than a failed rupture.In mega cisterna magna, unlike in DWM:
The cerebellum is not usually hypoplastic.
The fourth ventricle is of relatively normal shape.
Hydrocephalus is uncommon.There is debate as to whether this malformation is distinct from DWM or forms part of the "Dandy–Walker continuum".

Posterior fossa arachnoid cyst
An arachnoid cyst is a collection of cerebrospinal fluid (CSF) in the arachnoid mater. 10% of these occur in the posterior fossa.In a posterior fossa arachnoid cyst, unlike in DWM:
The cyst is clearly localised in a specific location separate from the fourth ventricle outlets.
The cerebellum is not hypoplastic, though it may be compressed by the cyst (mass effect).
The CSF flow in the cyst is not continuous with that of the fourth ventricle.
Hydrocephalus, if it occurs, is due to the cyst pressing on the cerebellum and compressing the cerebral aqueduct or fourth ventricle outlets.

Treatment
The main immediate goal of treatment is the control of hydrocephalus and the enlarged posterior fossa cyst, as these can lead to increased intracranial pressure and brain damage. A minority of those affected do not develop hydrocephalus and are treated based on any associated symptoms or condition.

Hydrocephalus/cyst
For hydrocephalus or the posterior fossa cyst, shunts are the mainstay of treatment. However, those with DWM have a higher rate of shunt-related complications than other patients with hydrocephalus (mainly due to the unconventional anatomy). One explanation for a failure of a shunt to reduce intracranial pressure in DWM has been that the cyst may herniate into the foramen magnum and form a scarring adhesion at the cervical junction, preventing it from shrinking again. If this occurs, a suboccipital decompression with duraplasty may be attempted.In DWM, it is not agreed whether a shunt should be placed in the fourth ventricle (a cystoperitoneal shunt, or CP shunt), the lateral ventricles (a ventriculoperitoneal shunt, or VP shunt) or both, due to conflicting studies on whether the cerebral aqueduct is affected by the malformation. However, a CP shunt almost always drains both the fourth and lateral ventricles in DWM, and according to strict definitions of the malformation, the aqueduct should be assumed open, though imaging is important to confirm this. Many authors therefore recommend the CP shunt as the logical option. However, it is associated with a high rate of complications, including shifting and overdrainage. Overdrainage can lead to subdural haematomas, a tethered spinal cord, due to scarring, or downward herniation of the cerebral hemispheres. Spennato et al. therefore recommend a flow-regulating or anti-syphon valve. On the other hand, VP shunts have a lower rate of complications than CP shunts and are recommended initially by some. However, they are less effective in DWM, and the elevated position of the tentorium should be considered before installing a VP shunt.In patients older than 1 year, endoscopic third ventriculostomy (ETV) may be considered as the first-line treatment. This less invasive procedure creates an artificial hole in the third ventricle to allow CSF to bypass any obstruction. It cannot be used on those with brain abnormalities such as agenesis of the corpus callosum, due to the risk of CSF escaping to other brain areas. A compressed brainstem is not a contraindication, however. ETV has a more modest success rate than shunts, as the hole often closes over. It is more likely to fail in younger patients (below 1 year), and its effects on the developing brain are not yet known. Cysts posterior to the cerebellum, presenting in children younger than 5 years, have been labeled developmental retrocerebellar cysts under a new classification in relation to the proposed neuroendoscopic management.Previously, craniotomy of the posterior fossa and excision of the cystic membrane was used, which was often unsuccessful in preventing cyst reformation and carried a degree of mortality. This may still be reserved for patients with repeated shunt failures/infections.

Other
Treatments for any other symptoms are generally focussed on the specific condition involved and may include supported education, physical therapy or other services. Genetic counselling may be offered to parents for future conceptions.

Prognosis
The prognosis is first and foremost dependent on the early and successful treatment of hydrocephalus, if present. The other significant factor affecting prognosis is the presence of a comorbid genetic condition or brain anomaly.Mortality rates from DWM are roughly 15%. In a study of Dandy–Walker variant (DWV), a mortality rate of 12.5% was observed. The most common cause of death is complications from hydrocephalus or its treatment. Untreated hydrocephalus can lead to increased intracranial pressure and brain damage. Shunts used to treat DWM have a moderate-to-good success rate, but they have a higher-than-average failure rate, which can result in failure to reduce the intracranial pressure or infection, such as meningitis. Complications from overdrainage such as subdural haematomas are also possible and can lead to mortality. Shunts in the fourth ventricle (cystoperitoneal shunts, or CP shunts) have a generally high rate of successful cyst and ventricle size reduction, especially in the cyst (at least 80%). With a shunt in the lateral ventricles (ventriculoperitoneal shunt, or VP shunt), studies have generally found a roughly 50% successful cyst size reduction rate, with successful ventricle size reduction roughly two thirds of the time.Other systemic or genetic conditions are often present with DWM, and each have their own significant effect on prognosis.

Epidemiology
The prevalence of DWM is estimated at between 1 in 25,000 to 1 in 50,000 </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 Clubfoot and can you explain it in depth? [/INST] Clubfoot is a birth defect where one or both feet are rotated inward and downward. Congenital clubfoot, is the most common congenital malformation of the foot with an incidence of 1 per 1000 births.  In approximately 50% of cases, clubfoot affects both feet, but it can present unilaterally causing one leg or foot to be shorter than the other. Most of the time, it is not associated with other problems. Without appropriate treatment, the foot deformity will persist and lead to pain and impaired ability to walk, which can have a dramatic impact on the quality of life.The exact cause is usually not identified. Both genetic and environmental factors are believed to be involved. There are two main types of congenital clubfoot: idiopathic (80% of cases) and secondary clubfoot (20% of cases). The idiopathic congenital clubfoot is a multifactorial condition that includes environmental, vascular, positional, and genetic factors. There appears to be hereditary component for this birth defect given that the risk of developing congenital clubfoot is 25% when a first-degree relative is affected. In addition, if one identical twin is affected, there is a 33% chance the other one will be as well. The underlying mechanism involves disruption of the muscles or connective tissue of the lower leg, leading to joint contracture. Other abnormalities are associated 20% of the time, with the most common being distal arthrogryposis and myelomeningocele. The diagnosis may be made at birth by physical examination or before birth during an ultrasound exam.The most common initial treatment is the Ponseti method, which is divided into two phases: 1) correcting of foot position and 2) casting at repeated weekly intervals. If the clubfoot deformity does not improve by the end of the casting phase, an Achilles tendon tenotomy can be performed. The procedure consists of a small posterior skin incision through which the tendon cut is made. In order to maintain the correct position of the foot, it is necessary to wear an orthopedic brace until 5 years of age.Initially, the brace is worn nearly continuously and then just at night. In about 20% of cases, further surgery is required. Treatment can be carried out by a range of healthcare providers and can generally be achieved in the developing world with few resources.Clubfoot occurs in 1 to 4 of every 1,000 live births, making it one of the most common birth defects affecting the legs. About 80% of cases occur in developing countries where there is limited access to care. Clubfoot is more common in firstborn children and males. It is more common among Māori people, and less common among Chinese people.

Epidemiology
Birth prevalence of clubfoot varies between 0.51 and 2.03/1,000 live births in Low to middle income countries. It is one of the most common birth defects affecting the legs. Clubfoot is more common in firstborn children and males, who are twice as likely to be affected as females. It is more common among Māori people, and less common among Chinese people.Clubfoot disproportionally affects those in low and middle-income countries (LMICs). About 80% of those with clubfoot, or approximately 100,000 children per year as of 2018, are born in LMICs.

History
Pharaohs Siptah and Tutankhamun had clubfoot, and the condition appeared in Egyptian paintings. Indian texts (c. 1000 BC) and Hippocrates (c. 400 BC) described treatment. In 1823, Delpech presented another way to treat patient with clubfoot. This new way was tenotomy, which means the cut of the Achilles tendon in those patients. As a surgical procedure it had its complications like infections.

Signs and symptoms
In clubfoot, feet are rotated inward and downward. The affected foot and leg may be smaller than the other, while in about half of cases, clubfoot affects both feet. Most of the time clubfoot is not associated with other problems.Clubfoot can be diagnosed by ultrasound of the fetus in more than 60% of cases. The earliest week of gestation in which the condition is diagnosed with a high degree of confidence was the 12th and the latest was the 32nd. Not all patients were diagnosed at an early stage. In 29% of fetuses the first ultrasound examination failed to detect the deformity which subsequently became obvious at a later examination. Clubfoot was diagnosed between 12 and 23 weeks of gestation in 86% of children and between 24 and 32 weeks of gestation in the remaining 14%.Without treatment the foot remains deformed and people walk on the sides or tops of their feet, which can cause calluses, foot infections, trouble fitting into shoes, pain, difficulty walking, and disability.

Causes
Hypotheses about the precise cause of clubfoot vary. However, research has found that genetics, environmental factors or a combination of both are associated with this condition.  Evidence suggests that the etiology of clubfoot is most likely multifactorial. A meta-analysis and systematic review found that the most clinically relevant risk factors for clubfoot were family history, paternal and maternal smoking, birthing parent obesity, gestational diabetes, amniocentesis, and the use of selective serotonin re-uptake inhibitors (SSRIS). Many findings agree that "it is likely there is more than one different cause and at least in some cases the phenotype may occur as a result of a threshold effect of different factors acting together." The most commonly associated conditions are distal arthrogryposis or myelomeningocele. The factors contributing to the development of clubfoot can be categorized as extrinsic and intrinsic factors.Extrinsic Factors
Factors that can influence the positioning of the fetal foot in uteru include oligohydramnios, breech presentation, Müllerian anomalies, multiple gestation, amniotic band sequence, or amniocentesis at <15 weeks of gestation. In cases that impede normal growth and position for longstanding period of times, clubfoot can be accompanied with other deformations and may be associated with developmental hip dysplasia. The theory of fetal growth arrest was proposed by Von Volkmann in 1863, and has been verified by other authors since. According to this theory, intrinsic errors or environmental insults during gestation prevents the correction of a equinovarus to pronated foot. Other researchers hypothesize that clubfoot may derive from external insults during gestation. For example, a research study found an alarming high incidence of club foot and limb contractures associated with iatrogenic amniotic leakage cause by early amniocentesis between the 11th and 12th week of gestation.Intrinsic Factors

Chromosomal abnormalities found in 30% and 2% of complex clubfoot and isolated clubfoot respectively. These include trisomy 18, 13, 21, sex chromosome abnormalities, micro-deletions and duplications.
Genetic Syndromes: Larsen, Gordon, Pierre-Robin, Meckel-Gruber, Roberts, Smith-Lemli-Opitz, TARP (Talipes equinovarus, Atrial septal defect, Robin sequence, Persistence of left superior vena cava).
Skeletal Dysplasias: Ellis van Creveld syndrome, diastrophic dysplasia, chondrodysplasia punctata, camptomelic dysplasia, atelosteogenesis, and mesomelic dysplasia.
Neuromuscular and Neurologic abnormalities: arthrogryposis multiplex congenita, myotonic dystrophy, spinal muscular atrophy,  neural tube defects, holoprosencephaly, and hydranencephaly.

Genetics
Clubfoot can be diagnosed prenatally as early as 13 weeks of gestation via ultrasound. According to the Society of Maternal-Fetal Medicine, a diagnostic testing for genetic causes is recommended when clubfoot is diagnoses prenatally. If prenatal screening is suspicious for aneuploidy, karyotype analysis or chromosomal microarray (CMA) may be performed. However, if patients decline diagnostic testing, Cell-Free DNA is another screening option to identify high-risk pregnancies for aneuploidy and it is not diagnostic.  The incidence of chromosomal abnormalities in fetuses with prenatal diagnosis of clubfoot is relatively low.  Overall, fetal ultrasound should be performed with a prenatal diagnosis of clubfoot in order to classify the condition as either complex or isolated because of the significant differences in rates of chromosomal abnormalities and outcomes between these two groups.If one identical twin is affected, there is a 33% chance the other one will be as well.Mutations in genes involved in muscle development are risk factors for clubfoot, specifically those encoding the muscle contractile complex (MYH3, TPM2, TNNT3, TNNI2 and MYH8). These can cause congenital contractures, including clubfoot, in distal arthrogryposis (DA) syndromes. Clubfoot can also be present in people with genetic conditions such as Loeys–Dietz syndrome and Ehlers-Danlos syndrome.Genetic mapping and the development of models of the disease have improved understanding of developmental processes. Its inheritance pattern is explained as a heterogenous disorder using a polygenic threshold model. The PITX1-TBX4 transcriptional pathway has become key to the study of clubfoot. PITX1 and TBX4 are uniquely expressed in the hind limb.

Diagnosis
Clubfoot is diagnosed through physical examination. Typically, babies are examined from head-to-toe shortly after they are born. There are four components of the clubfoot deformity:

Factors used to assess severity include the stiffness of the deformity (how much it can be corrected by manually manipulating the foot), the presence of skin creases at the arch and heel, and poor muscle consistency.
Sometimes, it is possible to detect clubfoot before birth using ultrasound. Prenatal diagnosis by ultrasound can allow parents to learn more about this condition and plan ahead for treatment after their baby is born.More testing and imaging is typically not needed, unless there is concern for other associated conditions.

Treatment
Treatment is usually with some combination of the Ponseti method and French method. The Ponseti method involves a combination of casting, Achilles tendon release, and bracing. It is widely used and highly effective under the age of two. The French method involves realignment, taping, and long-term home exercises and night splinting. It is also effective but outcomes vary and rely on heavy involvement of caregivers. Generally, the Ponseti method is preferred. Another technique, the Kite method, does not appear to be as effective. In about 20% of cases, additional surgery is required after initial treatment.

Ponseti method
The Ponseti method corrects clubfoot over the course of several stages.

Serial casting: First, the foot is manually manipulated into an improved position and held in place with a long leg cast which extends from the toes up to the thigh. After a week this cast is removed, the foot is re-manipulated, and placed into a new cast. This process repeats and the foot is gradually reshaped over the course of 4-6 serial casts, although some feet may require additional casts.
The goal of the initial cast is to align the forefoot with the hindfoot. Ponseti describes the forefoot as pronated in relation to the hindfoot, so supinating the forefoot and elevating the first metatarsal improves this alignment.
Subsequent casts are applied after stretching the foot with a focus on abducting the forefoot with lateral pressure at the talus, to bring the navicular laterally and improve the alignment of the talonavicular joint. In contrast to the Kite method of casting, it is important to avoid constraining the calcanocuboid joint. With each additional cast, the abduction is increased and this moves the hindfoot from varus into valgus. It is important to leave the ankle in equinus until the forefoot and hindfoot are corrected.
The final stage of casting is to correct the equinus. After fully abducting the forefoot with spontaneous correction of the hindfoot, an attempt is made to bring the ankle up and into dorsiflexion.  The foot must have the ability to dorsiflex to at least 10 degrees past 0 (neutral, or L position), although 15 degrees or more is better and preferred.  If the foot can not dorsiflex enough, the brace will not work/be tolerated.  If it is determined the foot can not dorsiflex at least 10 degrees, the Achilles Tenotomy surgical procedure is performed.
Achilles tendon release: At the end of the serial casting, most children have corrected cavus, adductus and varus deformities, but continue to have equinus deformity. To correct this, a procedure called an Achilles tendon release (commonly called Achilles tenotomy) is performed. Before the procedure, many centers place the child under sedation or monitored anesthesia care, although Ponseti recommended using local anesthetic alone. Next, the area around the heel is cleansed and numbed, and a small scalpel is used to cut the Achilles tendon. The incision is small so there is minimal bleeding and no need for stitches. The skin is covered with a small dressing, and the foot is placed into a final long leg cast in a fully corrected position. This cast is typically left in place for three weeks. During this time, the Achilles tendon will regrow in a lengthened position.
Bracing: After successful correction is achieved through serial casting and Achilles tenotomy, the foot must be kept in a brace to prevent it from returning to the deformed position over the first few years of a childs life. The brace is made up of two shoes or boots that are connected to each other by a bar that is bent under the shoes at 10-15 degrees, or curved to create 10-15 degrees dorsiflexion. This device is also called a foot abduction brace (FAB) or more generally boots and bar (BnB). At first, the brace is worn full-time (23 hours per day) on both feet, regardless of whether the clubfoot affects one or two feet. After 3 months of 23/7 wear, the brace is worn less frequently by gradually reducing hours a couple at a time, every couple months so that hours are down to 12-14 per day at or around a year old.  From this point on until at least 4–5 years, or even longer (6–9 years if needed), the brace is worn mostly while sleeping at night and during naps (12–14 hours per day).  Bracing is essential in preventing recurrence of the deformity and is a major determinant of a childs long-term outcome.The Ponseti method is highly effective with short-term success rates of 90%. However, anywhere from 14% to 41% of children experience a recurrence of the deformity. The most common reason for this is inadequate adherence to bracing, such as not wearing the brace properly, not keeping it on for the recommended length of time, or not using it every day. Children who do not follow proper bracing protocol have up to seven times higher recurrence rates than those who follow bracing protocol, as the muscles around the foot can pull it back into the abnormal position. Low parental education level and failure to understand the importance of bracing is a major contributor to non-adherence. Relapses are managed by repeating the casting process. Relapsed feet may also require additional, more extensive surgeries and have a reduced chance of achieving subsequent correction.Another reason for recurrence is a congenital muscle imbalance between the muscles that invert the ankle (tibialis posterior and tibialis anterior muscles) and the muscles that evert the ankle (peroneal muscles). This imbalance is present in approximately 20% of infants successfully treated with the Ponseti casting method, and makes them more prone to recurrence. This relapse is usually treated with Ponseti casting and can be done multiple times before resorting to surgery.  If after all non-surgical casting and bracing options have been exhausted, and when the child is over four years of age (many doctors prefer to wait until after seven years old), this can be addressed with a surgery to transfer the tibialis anterior tendon from its medial attachment (on the navicula) to a more lateral position (on the lateral cuneiform). The surgery requires general anesthesia and subsequent casting while the tendon heals, but it is a relatively minor surgery that re-balances the muscles of the foot without disturbing any joints.

French method
The French method is a conservative, non-operative method of clubfoot treatment that involves daily physical therapy for the first two months followed by thrice-weekly physical therapy for the next four months and continued home exercises following the conclusion of formal physical therapy. During each physical therapy session the feet are manipulated, stretched, then taped to maintain any gains made to the feets range of motion. Exercises may focus on strengthening the peroneal muscles, which is thought to contribute to long-term correction. After the two month mark, the frequency of physical therapy sessions can be weaned down to three times a week instead of daily, until the child reaches six months. After the conclusion of the physical therapy program, caregivers must continue performing exercises at home and splinting at night in order to maintain long-term correction.
Compared to the Ponseti method which uses rigid casts and braces, the French method uses tape which allows for some motion in the feet. Despite its goal to avoid surgery, the success rate varies and surgery may still be necessary. The Ponseti method is generally preferred over the French method.

Surgery
If non-operative treatments are unsuccessful or achieve incomplete correction of the deformity, surgery is sometimes needed. Surgery was more common prior to the widespread acceptance of the Ponseti method. The extent of surgery depends on the severity of the deformity. Usually, surgery is done at 9 to 12 months of age and the goal is to correct all the components of the clubfoot deformity at the time of surgery.
For feet with the typical components of deformity (cavus, forefoot adductus, hindfoot varus, and ankle equinus), the typical procedure is a Posteromedial Release (PMR) surgery. This is done through an incision across the medial side of the foot and ankle, that extends posteriorly, and sometimes around to the lateral side of the foot. In this procedure, it is typically necessary to release (cut) or lengthen the plantar fascia, several tendons, and joint capsules/ligaments. Typically, the important structures are exposed and then sequentially released until the foot can be brought to an appropriate plantigrade position. Specifically, it is important to bring the ankle to neutral, the heel into neutral, the midfoot aligned with the hindfoot (navicula aligned with the talus, and the cuboid aligned with the calcaneus). Once these joints can be aligned, thin wires are usually placed across these joints to hold them in the corrected position. These wires are temporary and left out through the skin for removal after 3–4 weeks. Once the joints are aligned, tendons (typically the Achilles, posterior tibialis, and flexor halluces longus) are repaired at an appropriate length. The incision (or incisions) are closed with dissolvable sutures. The foot is then casted in the corrected position for 6–8 weeks. It is common to do a cast change with anesthesia after 3–4 weeks, so that pins can be removed and a mold can be made to fabricate a custom AFO brace. The new cast is left in place until the AFO is available. When the cast is removed, the AFO is worn to prevent the foot from returning to the old position.For feet with partial correction of deformity with non-operative treatment, surgery may be less extensive and may involve only the posterior part of the foot and ankle. This might be called a posterior release. This is done through a smaller incision and may involve releasing only the posterior capsule of the ankle and subtalar joints, along with lengthening the Achilles tendon.
Surgery leaves residual scar tissue and typically there is more stiffness and weakness than with nonsurgical treatment. As the foot grows, there is potential for asymmetric growth that can result in recurrence of foot deformity that can affect the forefoot, midfoot, or hindfoot. Many patients do fine, but some require orthotics or additional surgeries. Long-term studies of adults with post-surgical clubfeet, especially those needing multiple surgeries, show that they may not fare as well in the long term. Some people may require additional surgeries as they age, though there is some dispute as to the effectiveness of such surgeries, in light of the prevalence of scar tissue present from earlier surgeries.

Developing world
Despite effective treatments, children in LMICs face many barriers such as limited access to equipment (specifically casting materials and abduction braces), shortages of healthcare professionals, and low education levels and socioeconomic status amongst caregivers and families. These factors make it difficult to detect and diagnose children with clubfoot, connect them to care, and train their caregivers to follow the proper treatment and return for follow-up visits. It is estimated that only 15% of those diagnosed with clubfoot receive treatment.In an effort to reduce the burden of clubfoot in LMICs, there have been initiatives to improve early diagnosis, organize high-volume Ponseti casting centers, utilize mid-level practitioners and non-physician health workers, engage families in care, and provide local follow-up in the persons community.

Cultural references
Hippolyte Tautain, the stableman at the Lion DOr public house in the 1856 novel Madame Bovary by Gustave Flaubert, has clubfoot. Charles Bovary tries to correct it, but the procedure is unsuccessful, and Tautain must have an amputation.
Philip Carey, the main character of the 1915 novel Of Human Bondage by W </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 Hypoplastic left heart syndrome and can you explain it in depth? [/INST] Hypoplastic left heart syndrome (HLHS) is a rare congenital heart defect in which the left side of the heart is severely underdeveloped and incapable of supporting the systemic circulation. It is estimated to account for 2-3% of all congenital heart disease. Early signs and symptoms include poor feeding, cyanosis, and diminished pulse in the extremities. The etiology is believed to be multifactorial resulting from a combination of genetic mutations and defects resulting in altered blood flow in the heart.Several structures can be affected including the left ventricle, aorta, aortic valve, or mitral valve all resulting in decreased systemic blood flow.Diagnosis can occur prenatally via ultrasound or shortly after birth via echocardiography. Initial management is geared to maintaining patency of the ductus arteriosus - a connection between the pulmonary artery and the aorta that closes shortly after birth.Patient subsequently undergoes a three-stage palliative repair over the next few years of life. The Norwood procedure is typically done within a few days of birth. The Glenn procedure is typically performed at three to six months of age. Finally the Fontan procedure is done sometime between the age of two and five years of age.
If left untreated patients with HLHS die within the first weeks of life while 70% of those that undergo three-staged palliative surgery reach adulthood. After surgery children with HLHS typically experience neurodevelopmental as well as motor delay and are at an increased risk of heart failure as adults.

Epidemiology
HLHS occurs in an estimated 1 out of 3,841 live births in the United States, or an estimated total of 1,025 live births per year in the US. Overall, it is estimated to make up 2-3% of all cases of congenital heart disease, and is the most common single-ventricle defect. It is thought to be more common in male infants, 1.5 times as common as in female infants. A recent systematic review found a slight decrease in prevalence of HLHS from 0.689/1000 in 1995 -1999, to 0.475/1000 in 2010 - 2017. This is thought to be due to improvements in prenatal detection and prenatal counseling and subsequent pregnancy.

Signs and symptoms
Closing of the ductus arteriosus in a heart that is severely underdeveloped on the left results in cyanosis and respiratory distress which can progress to cardiogenic shock and death. Early symptoms might include poor feeding or cyanosis that does not respond to oxygen administration. Peripheral pulses may be weak and extremities cool to the touch.HLHS often co-occurs with low birth weight and premature birth.In neonates with a small atrial septal defect, termed "restrictive", there is inadequate mixing of oxygenated and deoxygenated blood. These neonates quickly decompensate and develop acidosis and cyanosis.On EKG, right axis deviation and right ventricular hypertrophy are common, but not indicative of HLHS. Chest x-ray may show a large heart (cardiomegaly) or increased pulmonary vasculature. Neonates with HLHS do not typically have a heart murmur, but in some cases, a pulmonary flow murmur or tricuspid regurgitation murmur may be audible.Co-occurring tricuspid regurgitation or right ventricular dysfunction can cause hepatomegaly to develop.

Pathogenesis
The majority of HLHS cases are sporadic meaning they arise in patients with no family history of HLHS. Some cases may have a genetic component, as HLHS has been shown to be heritable and associated with specific gene mutations. Possible contributing factors may include intrauterine infarction, infectious changes, and a selective left ventricular cardiomyopathy.

Genetics
Genetic loci associated with HLHS include GJA1 (connexin 43), HAND1, NKX2.5, 10q22, and 6q23. There is a slight risk of recurrence in future pregnancies, estimated to be 2-4%, which increases to 25% in families with two affected children. This is thought to be mediated by genetic mutations with incomplete penetrance.HLHS is also associated with several genetic syndromes, including trisomy 13 (Patau syndrome), trisomy 18 (Edwards syndrome), partial trisomy 9, Turners syndrome (XO), Jacobsen syndrome (11q deletion syndrome), Holt-Oram syndrome, and Smith-Lemli-Opitz syndrome.

Altered Blood Flow
A popular theory termed the "no flow, no grow" hypothesis suggest that primary anatomic defects of the aortic and mitral valves lead to malformations of the left ventricle and its outflow tract.  These primary defects can be divided into those that lead to outflow tract obstruction or reduced left ventricular filling. Outflow tract obstruction leads to left ventricular hypertrophy and reduction in the left ventricular lumen. One example of this would be in the case of aortic stenosis. Aortic stenosis that occurs during fetal development results in added stress on the left ventricle in utero. This can eventually lead to decreased perfusion through the left ventricle which is believed to inhibit ventricular growth.

Pathophysiology
At birth, the ductus arteriosus is still open, and there is higher than normal resistance to blood flow in the lungs. This allows for adequate oxygenation via mixing between the atria and a normal appearance at birth. When the ductus begins to close and pulmonary vascular resistance decreases, blood flow through the ductus is restricted and flow to the lungs is increased.In typical anatomy, the left side of the heart receives oxygen-rich blood from the lungs and pumps it to the rest of the body. Patients with HLHS can have a number of cardiac malformations that ultimately lead to a diminutive left ventricle that is unable to supply sufficient blood flow to the rest of the body. There are three main anatomic variants of the disease differentiated by either stenosis or atresia of the aortic and mitral valve.Mitral atresia and aortic atresia (MA-AA) subtype is the most severe form of HLHS resulting in no blood flow entering the left ventricle at all resulting in no possibility of left ventricular output. In the mitral stenosis and aortic atresia (MS-AA) subtype blood is able to fill the left ventricle, however it is unable to be supplied to the systemic circulation via the hypoplastic ascending aorta. Lastly, the mildest form is the mitral stenosis and aortic stenosis (MS-AS) subtype. In these patients although the left ventricle is able to supply some blood flow to the rest of the body the overall left ventricular systemic output remains inadequate.In all of these cases blood is unable to be pumped to the rest of the body by the left ventricle. The neonate is reliant on blood flowing through an atrial septal defect to mix oxygenated and deoxygenated blood, and on a patent ductus arteriosus to allow blood to reach the aorta and the systemic circulation via the right ventricle. This is what defines HLHS as a "single ventricle" defect.Due to the underdevelopment of the left side of the heart in utero, the increased afterload causes hypertension of the left atrium, pulmonary edema, and therefore lung damage to the fetus before birth.

Diagnosis
Hypoplastic left heart syndrome can be diagnosed prenatally or after birth via echocardiography. Typical findings include a small left ventricle and aorta, abnormalities of the mitral and aortic valves, retrograde flow in the transverse arch of the aorta, and left-to-right flow between the atria. It is often recognized during the second trimester of pregnancy, between 18 and 24 weeks gestation.

Management
Medical
Without life-prolonging interventions, HLHS is fatal, but with intervention, an infant may survive. A cardiothoracic surgeon may perform a series of operations or a full heart transplant. While surgical intervention has emerged as the standard of care in the United States, other national health systems, notably in France, approach diagnosis of HLHS in a more conservative manner, with an emphasis on termination of pregnancy or compassionate care after delivery.Before surgery, the ductus must be kept open to allow blood-flow using medication containing prostaglandin. Air with less oxygen than normal is used for infants with hypoplastic left heart syndrome. These low oxygen levels increases the pulmonary vascular resistance (PVR) and thus improve blood flow to the rest of the body due to the greater pressure difference between the lungs and body.  Achieving oxygen levels below atmosphere requires the use of inhaled nitrogen. Nitric oxide is a potent pulmonary vasodilator, and thus reduces PVR and improves venous return. Any factor that increases PVR will impede right sided flow.

Surgical
Surgical operations to assist with hypoplastic left heart are complex and need to be individualized for each patient. A cardiologist must assess all medical and surgical options on a case-by-case basis.Currently, infants undergo either the staged reconstructive surgery (Norwood or Sano procedure within a few days of birth, Glenn or Hemi-Fontan procedure at 3 to 6 months of age, and the Fontan procedure at 1 1/2 to 5 years of age) or cardiac transplantation. Current expectations are that 70% of those with HLHS may reach adulthood. Many studies show that the higher the volume (number of surgeries performed) at a hospital, the lower the mortality (death) rate. Factors that increase an infants risk include lower birth weight, additional congenital anomalies, a genetic syndrome or those with a highly restrictive atrial septum. For patients without these additional risk factors, 5 year survival now approaches 80%.  Studies show that about 75% of those children who survive surgery show developmental delays in one or more areas, such as motor, cognitive, or language impairments, with about a third of single-ventricle children without a genetic syndrome having significant impairments. Current research focuses on charting the connections between neurodevelopment injuries, surgical and intensive care procedures, and genetic susceptibility with the goal of modifying interventions that impair neurodevelopmental and psychosocial outcomes.  An alternative to the traditional Norwood is the Hybrid procedure.Some physicians offer compassionate care, instead of the surgeries, which results in the childs death, usually within 2 weeks of birth.  Compassionate care is overseen by a physician, and may be carried out either in the hospital or at home.  However, due to the vast improvement of surgical intervention, with many hospitals achieving over 90% survival, there is debate on whether or not compassionate care should still be offered to families. A study in 2003 concluded that a selection of physicians who are experts in the care of children with HLHS were evenly split when asked what they would do if their own children were born with HLHS, with 1/3 stating that they would choose surgery, 1/3 stating that they would choose palliative (compassionate) treatment without surgery, and 1/3 stating that they are uncertain which choice they would make.The three-stage procedure is a palliative procedure (not a cure), as the childs circulation is made to work with only two of the hearts four chambers.

Norwood procedure
The first step is the Norwood procedure. In this procedure, the right ventricle is used to pump blood into the systemic circulation. Since the right ventricle is no longer directly pumping blood to the lungs, a shunt is required in order to pass deoxygenated blood through the lungs. Either the subclavian artery can be connected to the pulmonary circulation (Blalock-Taussig shunt), or a shunt is made directly from the right ventricle to the pulmonary circulation (Sano shunt). The narrow aorta is enlarged using a patch to improve blood flow to the body.During this time the baby may be medically fragile and have feeding problems because the heart is working very hard. There is a considerable degree of venous mixing in the right ventricle, leading to lower oxygenation saturation. In addition, both the Blalock-Taussig and the Sano shunts expose the lungs to systemic arterial pressures, leading to long-term pulmonary hypertension and eventually heart failure.

Hybrid procedure
The Hybrid procedure may be used in place of the Norwood.  The Hybrid procedure does not necessitate the use of heart-lung bypass or performing a sternotomy.  Instead of a six-hour surgery, the Hybrid typically takes one to two hours.  In this procedure, a stent is placed in the ductus arteriosus to maintain its patency, and bands are placed over both the left and right pulmonary artery branches to limit pressure and over-circulation to the lungs.  Outcomes with the Hybrid approach are comparable to those with the Norwood.

Glenn procedure
The second stage—the bidirectional Glenn or Hemi-Fontan (see also Kawashima procedure)—relieves some of the problems introduced by Stage I palliation. In this operation, the superior vena cava is ligated from the heart and connected to the pulmonary circulation. At this time, the Blalock-Taussig or Sano shunt is taken down. The lungs are no longer exposed to systemic arterial pressures, but much lower venous pressures. Although venous blood from the upper half of the body is no longer mixing with oxygenated blood in the right ventricle, there is still venous mixing from the lower half of the body, leading to some degree of oxygen desaturation.

Fontan procedure
The final procedure, the Fontan procedure, completes the repair of the hypoplastic left heart. Although there are several variations, the functional effect is to redirect venous blood from the lower body (through the inferior vena cava) away from the right atrium to the pulmonary artery. This should eliminate any mixing of oxygenated and deoxygenated blood in the right ventricle. The right ventricle performs the traditional job of the left, supplying the body with oxygenated blood, while the passive systemic venous pressure performs the traditional job of the right, passing deoxygenated blood to the lungs.

Fetal surgery
Interventions performed during fetal development are under investigation. In fetuses with hypoplastic left ventricles and an intact interatrial septum, percutaneous atrial septostomy has been attempted.

Prognosis
95% of untreated infants with HLHS die in the first weeks of life.Early survival has improved since the introduction of the Norwood procedure. Since there are no long-term studies of HLHS adults, statistics are usually derived from post-Fontan patients; it is estimated that 70% of HLHS patients may reach adulthood.Prognosis is dependent upon the health of the child, as there is an increased demand on respiratory and heart rate in infants during common childhood illnesses. This fragile population has little cardiac reserve to accommodate these demands and provide hemodynamic stability during illnesses.Children with HLHS and other comparable single-ventricle conditions, as a group, have poorer neurodevelopmental outcomes than their healthy peers. Deficits in language, executive functioning, and higher rates of anxiety and depression disorders have been demonstrated </s>


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<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 Median nerve and can you explain it in depth? [/INST] The median nerve is a nerve in humans and other animals in the upper limb. It is one of the five main nerves originating from the brachial plexus.
The median nerve originates from the lateral and medial cords of the brachial plexus, and has contributions from ventral roots of C5-C7 (lateral cord) and C8 and T1 (medial cord).The median nerve is the only nerve that passes through the carpal tunnel. Carpal tunnel syndrome is the disability that results from the median nerve being pressed in the carpal tunnel.

Structure
The median nerve arises from the branches from lateral and medial cords of the brachial plexus, courses through the anterior part of arm, forearm, and hand, and terminates by supplying the muscles of the hand.

Arm
After receiving inputs from both the lateral and medial cords of the brachial plexus, the median nerve enters the arm from the axilla at the inferior margin of the teres major muscle. It then passes vertically down and courses lateral to the brachial artery between biceps brachii (above) and brachialis (below). At first, it is lateral to the artery and lies anterior to the shoulder joint; it then crosses anteriorly to run medial to the artery in the distal arm and into the cubital fossa. Inside the cubital fossa, the median nerve passes medial to the brachial artery. The median nerve gives off an articular branch to the elbow joint. A branch to pronator teres muscle arise from the median nerve immediately above the elbow joint.

Forearm
The median nerve continues in the cubital fossa medial to the brachial artery and passes between the two heads of  the pronator teres, deep to the bicipital aponeurosis (aponeurosis of biceps) and superficial the brachialis muscle. It crosses the ulnar artery (branch of brachial artery) while being separated by the deep head of the pronator teres. It then travels between the flexor digitorum superficialis (above) and flexor digitorum profundus (below). The median nerve is accompanied by the median artery (a branch of anterior interosseous artery) during this course. Then,  about 5 cm above the flexor retinaculum (wrist), it emerges between the flexor digitorum superficialis (medially) and the flexor carpi radialis (laterally) into the hand.The main trunk of the median nerve innervates the superficial and deep groups of the muscles in the anterior compartment of the forearm with the exception of flexor carpi ulnaris. The median nerve does this by giving off two branches as it courses through the forearm:

Muscular branches are given off in the cubital fossa to supply flexor carpi radialis, palmaris longus, and flexor digitorum superficialis.
The anterior interosseous branch is given off in the upper part of the forearm, courses with the anterior interosseous artery and innervates flexor pollicis longus and the lateral half of flexor digitorum profundus (the ulnar half is supplied by ulnar nerve, as is the flexor carpi ulnaris muscle). It ends with its innervation of pronator quadratus. In addition to its supply to muscles, this nerve also supplies the distal radioulnar joint and wrist joint.The median nerve also gives off sensory and other branches in the forearm. The palmar cutaneous branch of the median nerve arises at the distal part of the forearm. It supplies sensory innervation to the thenar eminence of the palm and the central palm. Articular branches are given to the elbow joint and proximal radioulnar joint. Vascular branches supply the radial and ulnar arteries. Meanwhile, a communicating branch is given to the ulnar nerve.

Hand
The median nerve enters the hand through the carpal tunnel, deep to the flexor retinaculum along with the tendons of flexor digitorum superficialis, flexor digitorum profundus, and flexor pollicis longus. From there, it is divided into recurrent muscular branch and digital cutaneous branch:
The muscular branch (also known as recurrent branch) supplies the thenar muscles (opponens pollicis, abductor pollicis brevis, and superficial part of flexor pollicis brevis)
Digital cutaneous to the proper palmar digital branch and the common palmar digital branch: The proper palmar digital branch gives out three digital branches to the lateral one and a half digits (two digital branches to the thumb, one digital branch to the lateral side of the index finger). The digital branch to the index finger also supplies the first lumbrical. The common palmar digital branch divides further into two branches. Both the medial and lateral branches supply the second and third interdigital clefts with adjoining index, middle, and lateral half of ring finger. The lateral branch also supplies the second lumbrical.

Variation
The naturally occurring anomalies of the median nerve are:

Bifurcation of the median nerve typically occurs after the nerve exits the carpal tunnel; however, in a small percentage (5-10%) of individuals, the median nerve bifurcates more proximal in the carpal tunnel, wrist, or forearm.
During gestation, a median artery that serves the hand retracts.  However, in some individuals, the median artery does not retract and follows the course next to the median nerve into the hand.
Martin-Gruber anastomoses can occur when branches of the median nerve cross-over in the forearm and merge with the ulnar nerve to innervate portions of the forehand.
Riche-Cannieu anastomosis can occur when a connection exists between recurrent branch of the median nerve and deep branch of the ulnar nerve of the hand.

Function
The median nerve is the main nerve of the front of the forearm. It supplies the muscles of the front of the forearm and muscles of the thenar eminence, thus controlling the coarse movements of the hand. Therefore, it is also called "labourers nerve".

Arm
The median nerve has no voluntary motor or cutaneous function in the brachium </s>


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<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 Orthorexia nervosa and can you explain it in depth? [/INST] Orthorexia nervosa  (also known as orthorexia) (ON) is a proposed eating disorder characterized by an excessive preoccupation with eating healthy food. The term was introduced in 1997 by American physician Steven Bratman, M.D. He suggested that some peoples dietary restrictions intended to promote health may paradoxically lead to unhealthy consequences, such as social isolation, anxiety, loss of ability to eat in a natural, intuitive manner, reduced interest in the full range of other healthy human activities, and, in rare cases, severe malnutrition or even death.In 2009, Ursula Philpot, chair of the British Dietetic Association and senior lecturer at Leeds Metropolitan University, described people with orthorexia nervosa as being "solely concerned with the quality of the food they put in their bodies, refining and restricting their diets according to their personal understanding of which foods are truly pure." This differs from other eating disorders, such as anorexia nervosa and bulimia nervosa, where those affected focus on the quantity of food eaten.Orthorexia nervosa also differs from anorexia nervosa in that it does not disproportionally affect one gender. Studies have found that orthorexia nervosa is equally found in both men and women with no significant gender differences at all. Furthermore, research has found significant positive correlations between ON and both narcissism and perfectionism, but no significant correlation between ON and self esteem. This shows that high-ON individuals likely take pride over their healthy eating habits over others and that is the driving force behind their orthorexia as opposed to body image like anorexia.
Orthorexia nervosa is not recognized as an eating disorder by the American Psychiatric Association, and so is not mentioned as an official diagnosis in the widely used Diagnostic and Statistical Manual of Mental Disorders (DSM).

Signs and symptoms
Symptoms of orthorexia nervosa include "obsessive focus on food choice, planning, purchase, preparation, and consumption; food regarded primarily as source of health rather than pleasure; distress or disgust when in proximity to prohibited foods; exaggerated faith that inclusion or elimination of particular kinds of food can prevent or cure disease or affect daily well-being; periodic shifts in dietary beliefs while other processes persist unchanged; moral judgment of others based on dietary choices; body image distortion around sense of physical "impurity" rather than weight; persistent belief that dietary practices are health-promoting despite evidence of malnutrition."

Cause
There has been no investigation into whether there may be a biological cause specific to orthorexia nervosa. It may be a food-centered manifestation of obsessive-compulsive disorder, which has a lot to do with control.

Diagnosis
In 2016, formal criteria for orthorexia were proposed in the peer-reviewed journal Eating Behaviors by Thom Dunn and Steven Bratman. These criteria are as follows:
Criterion A.  Obsessive focus on "healthy" eating, as defined by a dietary theory or set of beliefs whose specific details may vary; marked by exaggerated emotional distress in relationship to food choices perceived as unhealthy; weight loss may ensue, but this is conceptualized as an aspect of ideal health rather than as the primary goal.  As evidenced by the following:

Compulsive behavior and/or mental preoccupation regarding affirmative and restrictive dietary practices believed by the individual to promote optimum health. (Footnotes to this criteria add: Dietary practices may include use of concentrated "food supplements." Exercise performance and/or fit body image may be regarded as an aspect or indicator of health.)
Violation of self-imposed dietary rules causes exaggerated fear of disease, sense of personal impurity and/or negative physical sensations, accompanied by anxiety and shame.
Dietary restrictions escalate over time, and may come to include elimination of entire food groups and involve progressively more frequent and/or severe "cleanses" (partial fasts) regarded as purifying or detoxifying. This escalation commonly leads to weight loss, but the desire to lose weight is absent, hidden or subordinated to ideation about healthy food.Criterion B. The compulsive behavior and mental preoccupation becomes clinically impairing by any of the following:

Malnutrition, severe weight loss or other medical complications from restricted diet
Intrapersonal distress or impairment of social, academic or vocational functioning secondary to beliefs or behaviors about healthy diet
Positive body image, self-worth, identity and/or satisfaction excessively dependent on compliance with self-defined "healthy" eating behavior.A diagnostic questionnaire has been developed for orthorexia sufferers, similar to questionnaires for other eating disorders, named the ORTO-15. However, Dunn and Bratman critique this survey tool as lacking appropriate internal and external validation.

Epidemiology
Results across scientific findings have yet to find a definitive conclusion to support whether nutrition students and professionals are at higher risk than other population subgroups, due to differing results in the research literature. There are only a few notable scientific works that, in an attempt to explore the breadth and depth of the still vaguely-understood illness, have tried to identify which groups in society are most vulnerable to its onset. This includes a 2008 German study, which based its research on the widespread suspicion that the most nutritionally-informed, such as university nutrition students, are a potential high-risk group for eating disorders, due to a substantial accumulation of knowledge on food and its relationship to health; the idea being that the more one knows about health, the more likely an unhealthy fixation about being healthy can develop. This study also inferred that orthorexic tendencies may even fuel a desire to study the science, indicating that many within this field might suffer from the disorder before commencing the course. However the results found that the students in the study, upon initial embarkation of their degree, did not have higher orthorexic values than other non-nutrition university students, and thus the report concluded that further research is needed to clarify the relationship between food-education and the onset of ON.Similarly, in a Portuguese study on nutrition tertiary students, the participants orthorexic scores (according to the ORTO-15 diagnostic questionnaire) actually decreased as they progressed through their course, as well as the overall risk of developing an eating disorder being an insignificant 4.2 percent. The participants also answered questionnaires to provide insight into their eating behaviours and attitudes, and despite this study finding that nutrition and health-science students tend to have more restrictive eating behaviours, these studies however found no evidence to support that these students have "more disturbed or disordered eating patterns than other students" These two aforementioned studies conclude that the more understanding of food one has is not necessarily a risk factor for ON, explaining that the data gathered suggests dietetics professionals are not at significant risk of it.
However, these epidemiologic studies have been critiqued as using a fundamentally flawed survey tool that inflates prevalence rates. Scholars have questioned both the reliability and validity of the ORTO-15.Most scientific findings tend to agree, however, young adults and adolescents are extremely susceptible to developing eating disorders. One study found that there was no relationship between BOT score and college major, which may indicate the prevalence of mental health issues and eating disorders on college campuses and that health and science majors are no longer the only ones affected More studies have also been conducted on the link between increased Instagram use and Orthorexia nervosa. The social media based healthy community has recently grown in popularity especially on platforms such as Instagram. The hashtag #food is one of the top 25 most popular hashtags on Instagram. A study that investigated this relationship found that increased use of Instagram correlated between symptoms of ON with no other social media platform having the same effect. With young adults and adolescents making up the majority of social media users, exposure to this type of content can lead to developing unhealthy behavior.

History
In a 1997 article in the magazine Yoga Journal, the American physician Steven Bratman coined the term "orthorexia nervosa" from the Greek ορθο- (ortho, "right" or "correct"), and όρεξις (orexis, "appetite"), literally meaning correct appetite, but in practice meaning correct diet. The term is modeled on anorexia, literally meaning "without appetite", as used in the definition of the condition anorexia nervosa </s>