<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 Twin and can you explain it in depth? [/INST] Twins are two offspring produced by the same pregnancy. Twins can be either monozygotic (identical), meaning that they develop from one zygote, which splits and forms two embryos, or dizygotic (non-identical or fraternal), meaning that each twin develops from a separate egg and each egg is fertilized by its own sperm cell. Since identical twins develop from one zygote, they will share the same sex, while fraternal twins may or may not.  In rare cases twins can have the same mother and different fathers (heteropaternal superfecundation).
In contrast, a fetus that develops alone in the womb (the much more common case, in humans) is called a singleton, and the general term for one offspring of a multiple birth is a multiple. Unrelated look-alikes whose resemblance parallels that of twins are referred to as doppelgängers.

Statistics
The human twin birth rate in the United States rose 76% from 1980 through 2009, from 9.4 to 16.7 twin sets (18.8 to 33.3 twins) per 1,000 births. The Yoruba people have the highest rate of twinning in the world, at 45–50 twin sets (90–100 twins) per 1,000 live births, possibly because of high consumption of a specific type of yam containing a natural phytoestrogen which may stimulate the ovaries to release an egg from each side. In Central Africa, there are 18–30 twin sets (or 36–60 twins) per 1,000 live births. In North America, South Asia (India, Pakistan, Bangladesh, Nepal), and Southeast Asia, the lowest rates are found; only 6 to 9 twin sets per 1,000 live births. North America and Europe have intermediate rates of 9 to 16 twin sets per 1,000 live births.Multiple pregnancies are much less likely to carry to full term than single births, with twin pregnancies lasting on average 37 weeks, three weeks less than full term. Women who have a family history of fraternal twins have a higher chance of producing fraternal twins themselves, as there is a genetically linked tendency to hyper-ovulate. There is no known genetic link for identical twinning. Other factors that increase the odds of having fraternal twins include maternal age, fertility drugs and other fertility treatments, nutrition, and prior births. Some women intentionally turn to fertility drugs in order to conceive twins.

Types and zygosity
The vast majority of twins are either dizygotic (fraternal) or monozygotic (identical). Less common variants are discussed further down the article.
Fraternal twins can be any of the following:

Female–female twins: Sometimes called sororal twins (25%).
Male–male twins: Sometimes called fraternal twins (25%).
Female-male twins: This is the most common pairing (50%), simply by virtue of it encompassing both "female-male" (25%) and "male-female" (25%) twins.Among non-twin births, male singletons are slightly (about five percent) more common than female singletons. The rates for singletons vary slightly by country. For example, the sex ratio of birth in the US is 1.05 males/female, while it is 1.07 males/female in Italy. However, males are also more susceptible than females to die in utero, and since the death rate in utero is higher for twins, it leads to female twins being more common than male twins.Zygosity is the degree of identity in the genome of twins.

Dizygotic (fraternal) twins
Dizygotic (DZ) or fraternal twins (also referred to as "non-identical twins", "dissimilar twins", "biovular twins", and, informally in the case of females, "sororal twins") usually occur when two fertilized eggs are implanted in the uterus wall at the same time. When two eggs are independently fertilized by two different sperm cells, fraternal twins result. The two eggs, or ova, form two zygotes, hence the terms dizygotic and biovular. Fraternal twins are, essentially, two ordinary siblings who happen to develop in the womb together and who are born at the same time, since they arise from two separate eggs fertilized by two separate sperm, just like ordinary siblings. This is the most common type of twin.Dizygotic twins, like any other siblings, will practically always have different sequences on each chromosome, due to chromosomal crossover during meiosis. Dizygotic twins share only 50 percent of each others genes, which resemble amongst siblings that are conceived and born at different times. Like any other siblings, dizygotic twins may look similar, particularly as they are the same age. However, dizygotic twins may also look very different from each other (for example, be of opposite sexes).
Studies show that there is a genetic proclivity for dizygotic twinning. However, it is only the mother who has any effect on the chances of having such twins; there is no known mechanism for a father to cause the release of more than one ovum. Dizygotic twinning ranges from six per thousand births in Japan (similar to the rate of monozygotic twins) to 14 and more per thousand in some African countries.Dizygotic twins are also more common for older mothers, with twinning rates doubling in mothers over the age of 35. With the advent of technologies and techniques to assist women in getting pregnant, the rate of fraternals has increased markedly.

Monozygotic (identical) twins
Monozygotic (MZ) or identical twins occur when a single egg is fertilized to form one zygote (hence, "monozygotic") which then divides into two separate embryos. The chances of having identical twins is relatively rare — around 3 or 4 in every 1,000 births.

Mechanism
Regarding spontaneous or natural monozygotic twinning, a recent theory proposes that monozygotic twins are probably formed when a blastocyst contains two inner cell masses (ICM), each of which will lead to a separate fetus, rather than by the embryo splitting while hatching from the zona pellucida (the gelatinous protective coating around the blastocyst).Monozygotic twins may also be created artificially by embryo splitting. It can be used as an expansion of in vitro fertilization (IVF) to increase the number of available embryos for embryo transfer.

Incidence
Monozygotic twinning occurs in birthing at a rate of about 3 in every 1000 deliveries worldwide (about 0.3% of the world population).The likelihood of a single fertilization resulting in monozygotic twins is uniformly distributed in all populations around the world. This is in marked contrast to dizygotic twinning, which ranges from about six per thousand births in Japan (almost similar to the rate of identical twins, which is around 4–5) to 15 and more per thousand in some parts of India and up to over 20 in some Central African countries. The exact cause for the splitting of a zygote or embryo is unknown.
IVF techniques are more likely to create dizygotic twins. For IVF deliveries, there are nearly 21 pairs of twins for every 1,000.

Genetic and epigenetic similarity
Monozygotic twins are genetically nearly identical and they are always the same sex unless there has been a mutation during development. The children of monozygotic twins test genetically as half-siblings (or full siblings, if a pair of monozygotic twins reproduces with another pair or with the same person), rather than first cousins. Identical twins do not have the same fingerprints however, because even within the confines of the womb, the fetuses touch different parts of their environment, giving rise to small variations in their corresponding prints and thus making them unique.Monozygotic twins always have the same genotype. Normally due to an environmental factor or the deactivation of different X chromosomes in female monozygotic twins, and in some extremely rare cases, due to aneuploidy, twins may express different sexual phenotypes, normally from an XXY Klinefelter syndrome zygote splitting unevenly.Monozygotic twins, although genetically very similar, are not genetically exactly the same. The DNA in white blood cells of 66 pairs of monozygotic twins was analyzed for 506,786 single-nucleotide polymorphisms known to occur in human populations. Polymorphisms appeared in 2 of the 33 million comparisons, leading the researchers to extrapolate that the blood cells of monozygotic twins may have on the order of one DNA-sequence difference for every 12 million nucleotides, which would imply hundreds of differences across the entire genome. The mutations producing the differences detected in this study would have occurred during embryonic cell-division (after the point of fertilization). If they occur early in fetal development, they will be present in a very large proportion of body cells.
Another cause of difference between monozygotic twins is epigenetic modification, caused by differing environmental influences throughout their lives. Epigenetics refers to the level of activity of any particular gene. A gene may become switched on, switched off, or could become partially switched on or off in an individual. This epigenetic modification is triggered by environmental events. Monozygotic twins can have markedly different epigenetic profiles. A study of 80 pairs of monozygotic twins ranging in age from three to 74 showed that the youngest twins have relatively few epigenetic differences. The number of epigenetic differences increases with age. Fifty-year-old twins had over three times the epigenetic difference of three-year-old twins. Twins who had spent their lives apart (such as those adopted by two different sets of parents at birth) had the greatest difference. However, certain characteristics become more alike as twins age, such as IQ and personality.In January 2021, new research from a team of researchers in Iceland was published in the journal Nature Genetics suggesting that identical twins may not be quite as identical as previously thought. The four-year study of monozygotic (identical) twins and their extended families revealed that these twins have genetic differences that begin in the early stages of embryonic development.

Polar body and semi-identical twins
A 1981 study of a deceased triploid XXX twin fetus without a heart showed that although its fetal development suggested that it was an identical twin, as it shared a placenta with its healthy twin, tests revealed that it was probably a polar body twin. The authors were unable to predict whether a healthy fetus could result from a polar body twinning. However, a study in 2012 found that it is possible for a polar body to result in a healthy fetus.In 2003, a study argued that many cases of triploidy arise from sesquizygotic (semi-identical) twinning.

Sesquizygotic twin type
See Semi-identical (sesquizygotic) twins below, under Unusual twinnings.

Degree of separation
The degree of separation of the twins in utero depends on if and when they split into two zygotes.  Dizygotic twins were always two zygotes.  Monozygotic twins split into two zygotes at some time very early in the pregnancy.  The timing of this separation determines the chorionicity (the number of placentae) and amniocity (the number of sacs) of the pregnancy.  Dichorionic twins either never divided (i.e.: were dizygotic) or they divided within the first 4 days. Monoamnionic twins divide after the first week.
In very rare cases, twins become conjoined twins. Non-conjoined monozygotic twins form up to day 14 of embryonic development, but when twinning occurs after 14 days, the twins will likely be conjoined. Furthermore, there can be various degrees of shared environment of twins in the womb, potentially leading to pregnancy complications.
It is a common misconception that two placentas automatically implies dizygotic twins, but if monozygotic twins separate early enough, the arrangement of sacs and placentas in utero is in fact indistinguishable from that of dizygotic twins.

Demographics
A 2006 study has found that insulin-like growth factor present in dairy products may increase the chance of dizygotic twinning. Specifically, the study found that vegan mothers (who exclude dairy from their diets) are one-fifth as likely to have twins as vegetarian or omnivore mothers, and concluded that "Genotypes favoring elevated IGF and diets including dairy products, especially in areas where growth hormone is given to cattle, appear to enhance the chances of multiple pregnancies due to ovarian stimulation."From 1980 to 1997, the number of twin births in the United States rose 52%. This rise can at least partly be attributed to the increasing popularity of fertility drugs and procedures such as IVF, which result in multiple births more frequently than unassisted fertilizations do. It may also be linked to the increase of growth hormones in food.

Ethnicity
About 1 in 90 human births (1.1%) results from a twin pregnancy. The rate of dizygotic twinning varies greatly among ethnic groups, ranging as high as about 45 per 1000 births (4.5%) for the Yoruba to 10% for Linha São Pedro, a tiny Brazilian settlement which belongs to the city of Cândido Godói. In Cândido Godói, one in five pregnancies has resulted in twins. The Argentine historian Jorge Camarasa has put forward the theory that experiments of the Nazi doctor Josef Mengele could be responsible for the high ratio of twins in the area. His theory was rejected by Brazilian scientists who had studied twins living in Linha São Pedro; they suggested genetic factors within that community as a more likely explanation. A high twinning rate has also been observed in other places of the world, including:

Igbo-Ora in Nigeria
Kodinhi, located in Kerala, India
Mohammadpur Umri, located in Uttar Pradesh, IndiaThe widespread use of fertility drugs causing hyperovulation (stimulated release of multiple eggs by the mother) has caused what some call an "epidemic of multiple births". In 2001, for the first time ever in the US, the twinning rate exceeded 3% of all births. Nevertheless, the rate of monozygotic twins remains at about 1 in 333 across the globe.
In a study on the maternity records of 5750 Hausa women living in the Savannah zone of Nigeria, there were 40 twins and 2 triplets per 1000 births. Twenty-six percent of twins were monozygotic. The incidence of multiple births, which was about five times higher than that observed in any western population, was significantly lower than that of other ethnic groups, who live in the hot and humid climate of the southern part of the country. The incidence of multiple births was related to maternal age but did not bear any association to the climate or prevalence of malaria.Twins are more common in people of African descent.

Predisposing factors
The predisposing factors of monozygotic twinning are unknown.
Dizygotic twin pregnancies are slightly more likely when the following factors are present in the woman:

She is of West African descent (especially Yoruba)
She is between the age of 30 and 40 years
She is greater than average height and weight
She has had several previous pregnancies.Women undergoing certain fertility treatments may have a greater chance of dizygotic multiple births. In the United States it has been estimated that by 2011 36% of twin births resulted from conception by assisted reproductive technology.The risk of twin birth can vary depending on what types of fertility treatments are used. With in vitro fertilisation (IVF), this is primarily due to the insertion of multiple embryos into the uterus. Ovarian hyperstimulation without IVF has a very high risk of multiple birth. Reversal of anovulation with clomifene (trade names including Clomid) has a relatively less but yet significant risk of multiple pregnancy.

Delivery interval
A 15-year German study of 8,220 vaginally delivered twins (that is, 4,110 pregnancies) in Hesse yielded a mean delivery time interval of 13.5 minutes. The delivery interval between the twins was measured as follows:

Within 15 minutes: 75.8%
16–30 minutes: 16.4%
31–45 minutes: 4.3%
46–60 minutes: 1.7%
Over 60 minutes: 1.8% (72 instances)The study stated that the occurrence of complications "was found to be more likely with increasing twin-to-twin delivery time interval" and suggested that the interval be kept short, though it noted that the study did not examine causes of complications and did not control for factors such as the level of experience of the obstetrician, the wish of the women giving birth, or the "management strategies" of the procedure of delivering the second twin.
There have also been cases in which twins are born a number of days apart. Possibly the worldwide record for the duration of the time gap between the first and the second delivery was the birth of twins 97 days apart in Cologne, Germany, the first of which was born on November 17, 2018.

Complications during pregnancy
Vanishing twins
Researchers suspect that as many as 1 in 8 pregnancies start out as multiples, but only a single fetus is brought to full term, because the other fetus has died very early in the pregnancy and has not been detected or recorded. Early obstetric ultrasonography exams sometimes reveal an "extra" fetus, which fails to develop and instead disintegrates and vanishes in the uterus. There are several reasons for the "vanishing" fetus, including it being embodied or absorbed by the other fetus, placenta or the mother. This is known as vanishing twin syndrome. Also, in an unknown proportion of cases, two zygotes may fuse soon after fertilization, resulting in a single chimeric embryo, and, later, fetus.

Conjoined twins
Conjoined twins (or the once-commonly used term "siamese") are monozygotic twins whose bodies are joined together during pregnancy. This occurs when the zygote starts to split after day 12 following fertilization and fails to separate completely. This condition occurs in about 1 in 50,000 human pregnancies.
Most conjoined twins are now evaluated for surgery to attempt to separate them into separate functional bodies. The degree of difficulty rises if a vital organ or structure is shared between twins, such as the brain, heart, liver or lungs.

Chimerism
A chimera is an ordinary person or animal except that some of their parts actually came from their twin or from the mother. A chimera may arise either from monozygotic twin fetuses (where it would be impossible to detect), or from dizygotic fetuses, which can be identified by chromosomal comparisons from various parts of the body. The number of cells derived from each fetus can vary from one part of the body to another, and often leads to characteristic mosaicism skin coloration in human chimeras. A chimera may be intersex, composed of cells from a male twin and a female twin. In one case DNA tests determined that a woman, Lydia Fairchild, mystifyingly, was not the mother of two of her three children; she was found to be a chimera, and the two children were conceived from eggs derived from cells of their mothers twin.

Parasitic twins
Sometimes one twin fetus will fail to develop completely and continue to cause problems for its surviving twin. One fetus acts as a parasite towards the other.
Sometimes the parasitic twin becomes an almost indistinguishable part of the other, and sometimes this needs to be treated medically.

Partial molar twins
A very rare type of parasitic twinning is one where a single viable twin is endangered when the other zygote becomes cancerous, or "molar". This means that the molar zygotes cellular division continues unchecked, resulting in a cancerous growth that overtakes the viable fetus. Typically, this results when one twin has either triploidy or complete paternal uniparental disomy, resulting in little or no fetus and a cancerous, overgrown placenta, resembling a bunch of grapes.

Miscarried twin
Occasionally, a woman will suffer a miscarriage early in pregnancy, yet the pregnancy will continue; one twin was miscarried but the other was able to be carried to term. This occurrence is similar to the vanishing twin syndrome, but typically occurs later, as the twin is not reabsorbed.

Low birth weight
It is very common for twins to be born at a low birth weight. More than half of twins are born weighing less than 5.5 pounds (2.5 kg), while the average birth weight of a healthy baby should be around 6–8 pounds (3–4 kg). This is largely due to the fact that twins are typically born premature. Premature birth and low birth weights, especially when under 3.5 pounds (1.6 kg), can increase the risk of several health-related issues, such as vision and hearing loss, mental disabilities, and cerebral palsy. There is an increased possibility of potential complications as the birth weight of the baby decreases.

Twin-to-twin transfusion syndrome
Monozygotic twins who share a placenta can develop twin-to-twin transfusion syndrome. This condition means that blood from one twin is being diverted into the other twin. One twin, the donor twin, is small and anemic, the other, the recipient twin, is large and polycythemic. The lives of both twins are endangered by this condition.

Stillbirths
Stillbirths occurs when a fetus dies after 20 weeks of gestation. There are two types of stillbirth, including intrauterine death and intrapartum death. Intrauterine death occurs when a baby dies during late pregnancy. Intrapartum death, which is more common, occurs when a baby dies while the mother is giving birth. The cause of stillbirth is often unknown, but the rate of babies who are stillborn is higher in twins and multiple births. Caesareans or inductions are advised after 38 weeks of pregnancy for twins, because the risk of stillbirth increases after this time.

Heterotopic pregnancy
Heterotopic pregnancy is an exceedingly rare type of dizygotic twinning in which one twin implants in the uterus as normal and the other remains in the fallopian tube as an ectopic pregnancy. Ectopic pregnancies must be resolved because they can be life-threatening to the mother. However, in most cases, the intrauterine pregnancy can be salvaged.

Management of birth
For otherwise healthy twin pregnancies where both twins are head down a trial of vaginal delivery is recommended at between 37 and 38 weeks. Vaginal delivery in this case does not worsen the outcome for the infant as compared with Caesarean section.  There is controversy on the best method of delivery where the first twin is head first and the second is not. When the first twin is not head down a caesarean section is often recommended.  It is estimated that 75% of twin pregnancies in the United States were delivered by caesarean section in 2008. In comparison, the rate of caesarean section for all pregnancies in the general population varies between 14% and 40%. In twins that share the same placenta, delivery may be considered at 36 weeks. For twins who are born early, there is insufficient evidence for or against placing preterm stable twins in the same cot or incubator (co-bedding).

Human twin studies
Twin studies are utilized in an attempt to determine how much of a particular trait is attributable to either genetics or environmental influence. These studies compare monozygotic and dizygotic twins for medical, genetic, or psychological characteristics to try to isolate genetic influence from epigenetic and environmental influence. Twins that have been separated early in life and raised in separate households are especially sought-after for these studies, which have been used widely in the exploration of human nature.  Classical twin studies are now being supplemented with molecular genetic studies which identify individual genes.

Unusual twinnings
Bi-paternal twins
This phenomenon is known as heteropaternal superfecundation. One 1992 study estimates that the frequency of heteropaternal superfecundation among dizygotic twins, whose parents were involved in paternity suits, was approximately 2.4%; see the references section, below, for more details.Dizygotic twins from biracial couples can sometimes be mixed twins, which exhibit differing ethnic and racial features. One such pairing was born in London in 1993 to a white mother and Caribbean father.

Monozygotic twins of different sexes
Among monozygotic twins, in extremely rare cases, twins have been born with different sexes (one male, one female). When monozygotic twins are born with different sexes it is because of chromosomal defects.  The probability of this is so small that multiples having different sexes is universally accepted as a sound basis for in utero clinical determination that the multiples are not monozygotic.
Another abnormality that can result in monozygotic twins of different sexes is if the egg is fertilized by a male sperm but during cell division only the X chromosome is duplicated. This results in one normal male (XY) and one female with Turner syndrome (45,X).  In these cases, although the twins did form from the same fertilized egg, it is incorrect to refer to them as genetically identical, since they have different karyotypes.

Semi-identical (sesquizygotic) twins
Monozygotic twins can develop differently, due to their genes being differently activated. More unusual are "semi-identical twins", also known as "sesquizygotic". As of 2019, only two cases have been reported. These "half-identical twins" are hypothesized to occur when an unfertilized egg cleaves into two identical attached ova, both of which are viable for fertilization. Both ova are then fertilized, each by a different sperm, and the coalesced zygotes undergo further cell duplications developing as a chimeric blastomere. If this blastomere then undergoes a twinning event, two embryos will be formed, with different paternal genetic information and identical maternal genetic information.
This results in a set of twins with identical gene sequence from the mothers side, but different sequences from the fathers side. Cells in each fetus carry chromosomes from either sperm, resulting in chimeras. This form had been speculated until only recently being recorded.

In 2007, a study reported a case of a pair of living twins, which shared an identical set of maternal chromosomes, while each having a distinct set of paternal chromosomes, albeit from the same man, and thus they most likely share half of their fathers genetic makeup. The twins were both found to be chimeras. One was an intersex XX, and one a XY male. The exact mechanism of fertilization could not be determined but the study stated that it was unlikely to be a case of polar body twinning.In 2019, a second case of sesquizygotic twins was reported and molecular evidence of the phenomenon was documented by Gabbett and Fisk. In this case, the twins shared 100% of their maternal chromosomes and 78% of their paternal genomic information. The authors postulate two sperm from the same man fertilized an ovum simultaneously. The chromosomes assorted themselves through heterogonesis to form three cell lines. The purely paternal cell line died out due to genomic imprinting lethality, while the other two cell lines, each conisiting of the same maternal DNA but only 50% identical paternal DNA, formed a morula which subsequently split into twins

Mirror image twins
Mirror image twins result when a fertilized egg splits later in the embryonic stage than normal timing, around day 9–12. This type of twinning could exhibit characteristics with reversed asymmetry, such as opposite dominant handedness, dental structure, or even organs (situs inversus). If the split occurs later than this time period, the twins risk being conjoined. There is no DNA-based zygosity test that can determine if twins are indeed mirror image. The term "mirror image" is used because the twins, when facing each other, appear as matching reflections.

Language development
There have been many studies highlighting the development of language in twins compared to single-born children. These studies have converged on the notion that there is a greater rate of delay in language development in twins compared to their single-born counterparts.  The reasons for this phenomenon are still in question; however, cryptophasia was thought to be the major cause.  Idioglossia is defined as a private language that is usually invented by young children, specifically twins. Another term to describe what some people call "twin talk" is cryptophasia where a language is developed by twins that only they can understand.  The increased focused communication between two twins may isolate them from the social environment surrounding them.  Idioglossia has been found to be a rare occurrence and the attention of scientists has shifted away from this idea.  However, there are researchers and scientists that say cryptophasia or idioglossia is not a rare phenomenon. Current research is looking into the impacts of a richer social environment for these twins to stimulate their development of language.

Animals
Twins are common in many mammal species, including cats, sheep, ferrets, giant pandas,Cow,dolphins, dogs, deer, marmosets, tamarins, and elephants. The incidence of twinning among cattle is about 1–4%, and research is underway to improve the odds of twinning, which can be more profitable for the breeder if complications can be sidestepped or managed. A female calf that is the twin of a bull becomes partially masculinized and is known as a freemartin.

See also
References
Further reading
Bacon, Kate. Twins in Society: Parents, Bodies, Space, and Talk (Palgrave Macmillan; 2010) 221 pages; explores the experience of child twins, adult twins, and parents of twins, with a focus on Britain.
Nieuwint, Aggie; Van Zalen-Sprock, Rieteke; Hummel, Pieter; Pals, Gerard; Van Vugt, John;  et al. (1999). "Identical twins with discordant karyotypes". Prenatal Diagnosis. 19 (1): 72–6. doi:10.1002/(SICI)1097-0223(199901)19:1<72::AID-PD465>3.0.CO;2-V. PMID 10073913. S2CID 19112883.
Wenk RE, Houtz T, Brooks M, Chiafari FA (1992). "How frequent is heteropaternal superfecundation?". Acta Geneticae Medicae et Gemellologiae. 41 (1): 43–7. doi:10.1017/S000156600000249X. PMID 1488855. S2CID 23507167.
Girela, Eloy; Lorente, Jose A.; Alvarez, J. Carlos; Rodrigo, Maria D.; Lorente, Miguel;  et al. (1997). "Indisputable double paternity in dizygous twins". Fertility and Sterility. 67 (6): 1159–61. CiteSeerX 10.1.1.378.4082. doi:10.1016/S0015-0282(97)81456-2. PMID 9176461.
Shinwell ES, Reichman B, Lerner-Geva L, Boyko V, Blickstein I (September 2007). ""Masculinizing" effect on respiratory morbidity in girls from unlike-sex preterm twins: a possible transchorionic paracrine effect". Pediatrics. 120 (3): e447–53. doi:10.1542/peds.2006-3574. PMID 17766488. S2CID 20498737. Retrieved 2008-10-06.
Lummaa V, Pettay JE, Russell AF (June 2007). "Male twins reduce fitness of female co-twins in humans". Proceedings of the National Academy of Sciences of the United States of America. 104 (26): 10915–20. Bibcode:2007PNAS..10410915L. doi:10.1073/pnas.0605875104. PMC 1904168. PMID 17576931.
Schein, Elyse; Paula Bernstein (2007). Identical Strangers: A Memoir of Twins Separated and Reunited. New York: Random House. ISBN 978-1-4000-6496-0. OCLC 123390922.
Helle, Samuli; Virpi Lummaa; Jukka Jokela (2004). "Selection for Increased Brood Size in Historical Human Populations" (PDF). Evolution. 58 (2): 430–436. doi:10.1111/j.0014-3820.2004.tb01658.x. PMID 15068359. S2CID 9460009. Archived from the original (PDF) on 2008-10-02. Retrieved 2008-10-02.
"TWINS Guide to the First Year" (PDF). TWINS Magazine. Fort Collins, Colorado. 2008. Archived from the original (PDF) on 2008-10-30 </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 Primary juvenile glaucoma and can you explain it in depth? [/INST] Primary juvenile glaucoma is glaucoma that develops due to ocular hypertension and is evident either at birth or within the first few years of life. It is caused due to abnormalities in the anterior chamber angle development that obstruct aqueous outflow in the absence of systemic anomalies or other ocular malformation.

Presentation
The typical infant who has congenital glaucoma usually is initially referred to an ophthalmologist because of apparent corneal edema. The commonly described triad of epiphora (excessive tearing), blepharospasm and photophobia may be missed until the corneal edema becomes apparent.

Systemic associations
Two of the more commonly encountered disorders that may be associated with congenital glaucoma are Aniridia and Sturge-Weber syndrome.

Genetics
JOAG is an autosomal dominant condition. The primary cause is the myocilin protein dysfunction. Myocilin gene mutations are identified in approximately 10% of patients affected by juvenile glaucoma.

Diagnosis
The diagnosis is clinical. The intraocular pressure (IOP) can be measured in the office in a conscious swaddled infant using a Tonopen or hand-held Goldmann tonometer. Usually, the IOP in normal infants is in the range of 11-14 mmHg. Buphthalmos and Haabs striae can often be seen in case of congenital glaucoma.

Differential diagnosis
Corneal cloudiness may have myriad of causes. Corneal opacity that results from hereditary dystrophies is usually symmetric.
Corneal enlargement may result from megalocornea, a condition in which the diameter of the cornea is larger than usual and the eye is otherwise normal.

Treatment
The preferred treatment of congenital glaucoma is surgical, not medical. The initial procedures of choice are goniotomy or trabeculotomy if the cornea is clear, and trabeculectomy ab externo if the cornea is hazy. The success rates are similar for both procedures in patients with clear corneas </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 Neutrophilic eccrine hidradenitis and can you explain it in depth? [/INST] Neutrophilic eccrine hidradenitis (NEH) usually is a cutaneous complication of chemotherapy, but it can also occur for other reasons. It consists of fever and non specific skin lesions. It is rare, and self-limited.

Signs and symptoms
Fever and a non specific skin eruption – with reddening (erythema) and swelling (oedema) of the skin – are the most common symptoms of NEH. Patients usually present with the skin eruption 1-2 weeks after use of the cytotoxic drug. Sometimes, the skin eruption can be painful. Skin eruptions can be located on the extremities, trunk, and face. Severe lesions are rare, and can mimic cellulitis. Generalised lesions resembling erythema multiforme have been reported.

Cause
The overwhelming majority of neutrophilic eccrine hidradenitis (NEH) is seen in people with cancer, especially leukaemia, who receive chemotherapy with a cytotoxic drug. These include: Bleomycin, chlorambucil, cyclophosphamide, cytarabine, doxorubicin, lomustine, mitoxantrone, topotecan, and vincristine.NEH was first described in 1982 in a patient with acute myeloid leukaemia (AML) who had received cytarabine as chemotherapy.Cancer itself, infections, and other medicinal drugs also can lead to NEH. NEH has been reported in patients with cancer who have not received any form of chemotherapy (i.e., as a paraneoplastic syndrome), in patients with HIV and/or AIDS, and after the use of paracetamol (acetaminophen). Also the use of targeted agents can lead to NEH, e.g. imatinib, a tyrosine kinase inhibitor.NEH has also been described without any known reason (idiopathic cases), including idiopathic cases in children.The exact cause of NEH is unknown </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 Spermatocele and can you explain it in depth? [/INST] Spermatocele is a fluid-filled cyst that develops at the top of the testicle of the epididymis. The fluid is usually a clear or milky white color and may contain sperm. Spermatoceles are typically filled with spermatozoa and they can vary in size from several millimeters to many centimeters. Small spermatoceles are relatively common, occurring in an estimated 30 percent of males. They are generally not painful. However, some people may experience discomfort such as a dull pain in the scrotum from larger spermatoceles. They are not cancerous, nor do they cause an increased risk of testicular cancer. Additionally, unlike varicoceles, they do not reduce fertility.

History
"Spermatocele" is originally derived from the Greek term spermatos (sperm) and kele (cavity or mass). Oftentimes, "epididymal cyst" has been used interchangeably with "spermatocele." However, it is important to note their differences. Epididymal cysts may appear anywhere along or within the epididymis and do not contain sperm, whereas spermatoceles may contain sperm. Epididymal cysts have been shown to occur more frequently in children before reaching puberty.

Epidemiology
Spermatoceles usually affect men who are middle-aged and can, although rarely, affect children during puberty. The incidence rate is around 5-20% for children. It is estimated that approximately 30 percent of men have been diagnosed with small spermatoceles while less have larger spermatoceles. The incidence of spermatoceles increases as men age. Before puberty, children from the male sex may develop a similar benign mass called epididymis cyst. Although both epididymis cyst and spermatocele may be referred as the same, the epididymis cyst does not contain sperm and it can occur anywhere within the epididymis. It can be differentiated through an ultrasound imagining. Epididymis cysts larger than 10mm in diameter are recommended for surgery but if there is no problem then surgery is discouraged as it can affect fertility in the future.

Chronic infectious epididymitis
Chronic infectious epididymitis is rare. Some signs and symptoms include localized tenderness and swelling in the epididymis, which are different from any tenderness/abnormality present in the testis, these are usually not found in lower urinary tract. Chronic infectious epididymitis may be diagnosed in healthy adolescents as well as men. Some factors that predispose individuals to chronic infectious epididymitis include sexual activity, heavy physical exertion, and bicycle or motorcycle riding. Those diagnosed with chronic or recurrent epididymitis should receive a CT scan with contrast and a prostate ultrasonography to rule out structural abnormality of the urinary tract. If suspected to have chronic infectious epididymitis, consider getting a urinalysis, urine culture, and urine nucleic acid amplification tests for presence of Neisseria gonorrhoeae and Chlamydia trachomatis. Management of chronic infectious epididymitis is similar to management of acute infectious epididymitis, rarely does treatment extend to surgical management.

Chronic noninfectious epididymitis
Chronic noninfectious epididymitis – Trauma, autoimmune disease, or vasculitis can cause chronic noninfectious epididymitis, but no clear cause or origin of the disease is found in most cases.  Noninfectious epididymitis that happen spontaneously might be caused by the reflux of urine through the ejaculatory ducts and vas deferens into the epididymis, producing inflammation that leads to swelling and ductal obstruction. Men with history of vasectomy are also predisposed to chronic nonifectious epididymitis. Typical inciting factors include prolonged periods of sitting (long plane or car travel, sedentary desk jobs) or vigorous exercise (heavy lifting). Acute infectious epididymitis are often associated with more tenderness and swelling, whereas chronic noninfectious epididymitis tend to have less tenderness and swelling upon examination. Thorough past medical history and physical examination can help with determining the diagnosis. It is often that individuals with chronic noninfectious epididymitis will present with a history of a lack of symptom improvement while on antibiotic therapy. Management of chronic noninfectious epididymitis includes scrotal elevation, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (unless unable to take for medical reasons), and it is recommended that individuals avoid physical activities that may cause said symptoms. Those with sedentary jobs or often experience prolonged periods of time sitting should practice physical mobility more frequently.

Risk Factors
It is not well known what may be causing the growth of a spermatocele. It has been observed that pregnant women who were prescribed diethylstilbestro (DES) to prevent pregnancy complications, such as miscarriage, and gave birth to a son most likely increased the risk of the son to develop a spermatocele in the future. However, doctors stopped prescribing this medication in 1971 since it increased the risk of women developing a rare vaginal cancer.

Causes
Spermatoceles can originate as diverticulum from the tubules found in the head of the epididymis. Sperm accumulation gradually causes the diverticulum to increase in size, causing a spermatocele. Since there are many tubules connecting the epididymis to the testis, a blockage in one of the tubules may lead to formation of a cyst. In many instances they appear to occur spontaneously without any preceding instances of injury.Scarring of any part of the epididymis due to trauma or inflammation can cause it to become obstructed and in turn form a spermatocele.

Diagnosis
Spermatoceles can be discovered as incidental scrotal masses found on physical examination by a physician or by self-inspection of the scrotum and testicles. The various types of diagnosis for spermatocele types include hydrocele, varicocele, hernia, simple epididymal cyst, and neoplasm.The primary care physician may diagnose and manage benign causes of scrotal masses such as hydrocele, varicocele and spermatocele. However, if a "must not miss" diagnoses related to testicular masses such as testicular torsion, epididymitis, acute orchitis, strangulated hernia and testicular cancer is suspected, the family physician must refer to a urologist.
Finding a painless, cystic mass at the head of the epididymis that is clearly separate from the testicle can indicate a spermatocele. Shining a light through the mass through a process known as transillumination can also help differentiate between a fluid-filled cyst and a tumor, which would not allow as much light to pass. If uncertainty exists, ultrasonography of the scrotum can confirm the presence of a spermatocele. The location and history of any scrotal masses are crucial in determining whether or not the mass is benign or malignant. Lab tests such as a complete blood count (CBC test) or urine test can also be conducted to check for any possible infection or signs of inflammation.Spermatoceles come in varying sizes and shapes. Some spermatoceles are very small and can only be detected through an ultrasound. More commonly seen are spermatoceles that are a pea-sized lump. They tend to form above or behind a testicle and have a shape and size that looks like a pea. Larger growths have been reported to look similar to a third testicle and can be very discomforting. For those who are affected with large spermatoceles, some have reported feeling pain, heaviness, and fullness in the affected testicle.

When to see a doctor
If a person is experiencing pain and/or swelling in the scrotum or if a person notices a physical difference such as a mass during a testicular self-exam then they must seek medical attention quickly to help rule out any other causes and begin treatment.

Special Populations
Spermatoceles in Children
Epididymal cysts may arise in children due to numerous different reasons. They may even originate from a disturbance in endocrine factors during the development of the embryo. The incidence of these cysts are possibly linked to boys who are exposed to diethylstilbestrol, an estrogen medication, while in the fetus.Although the evidence and information for incidence of spermatoceles in children is lacking, there are general management guidelines for caregivers who may encounter spermatoceles in their children. Epididymal cysts are typically benign in nature. However, caregivers should take note of any discomfort and symptoms in children, including but not limited to, erythema, scrotal edema or swelling. Epididymal cysts appear in approximately 70% of boys who present as asymptomatic. The diagnosis of epididymal cysts in children can be discovered upon physical examination and eventually confirmed via ultrasound.

Treatment
Small cysts as well as asymptomatic larger cysts are better left alone and carefully observed. However, treatment can be considered if the cysts are causing discomfort/pain, enlarging in size, or per patient request. There are a few different treatment options, ranging in levels of invasiveness.

Medications
Certain drugs such as oral analgesics or anti-inflammatory medications can be taken by mouth to decrease spermatocele-related symptoms such as pain and/or swelling. At the moment, there is no medication that can inhibit the production of a spermatocele or cure it. Common medications recommended by doctors are acetaminophen (Tylenol) that can treat pain. To treat the inflammation and pain, non-steroidal anti-inflammatory drugs (NSAIDs) are recommended such as ibuprofen (Motrin, Advil), naproxen (Aleve), and others. Antibiotics may also be prescribed in cases where risk of infection and discomfort is indicated.

Medical Procedures
Aspiration and sclerotherapy are treatments that remove fluid from the spermatocele and seal the spermatocele sac closed from further fluid build-up, respectively. Due to a higher risk of epididymis damage, fertility problems, and further recurrences, these procedures are not recommended and not commonly used.

Surgical Treatments
Surgical treatments must be thoroughly discussed with people prior to any final decisions. Different types of surgical procedures may be chosen based on the extent of risk.A short procedure called a spermatocelectomy can be performed for spermatoceles that cause irritating symptoms. This standard procedure can be performed in an outpatient setting with the use of local or general anesthesia. This procedure typically consists of removing the spermatocele and a portion of the epididymis. The risk of epididymal injury is 17.12%. This incident may happen when the spermatocele is being dissected from the head of the epididymis. Spermatocelectomy can cause complications such as hematoma, wound infection, scrotal abscess as well as recurrence. After surgery, the doctor may recommend to apply ice packs for several days to help reduce swelling. Oral pain medications can also be taken for a few days to reduce discomfort. In addition, the patient returns 2–6 weeks after to inspect any progress/complications. If received a vasectomy, then two semen samples must be collected and analyzed after 6–12 weeks post-operation and several ejaculations. The centrifuged semen samples are used to look for the absence of viable sperm in the semen.

Risk of Complications
After surgical removal, it is possible that the pain will persist and recurrence can occur. Fertility may be compromised with these surgical procedures, so people may consider postponing surgery until after having children </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 Cutis laxa and can you explain it in depth? [/INST] Cutis laxa  or pachydermatocele is a group of rare connective tissue disorders in which the skin becomes inelastic and hangs loosely in folds.

Signs and symptoms
It is characterised by skin that is loose, hanging, wrinkled, and lacking in elasticity. The loose skin can be either generalised or localised. Biopsies have shown reduction and degeneration of dermal elastic fibres in the affected areas of skin. The loose skin is often most noticeable on the face, resulting in a prematurely aged appearance. The affected areas of skin may be thickened and dark. In addition, the joints may be loose (hypermobile) because of lax ligaments and tendons. When cutis laxa is severe, it can also affect the internal organs. The lungs, heart (supravalvular pulmonary stenosis), intestines, or arteries may be affected with a variety of severe impairments. In some cases, hernias and outpouching of the bladder can be observed. Patients can also present with whites of the eyes that are blue.

Causes
In many cases, cutis laxa is inherited. Autosomal dominant, autosomal recessive, and X-linked recessive forms have been described, but acquired forms also occur.Cutis laxa is associated with deficient or absent elastin fibers in the extracellular matrix. This can be related to decreased elastin synthesis or structural defects in the extracellular matrix.Cutis laxa may be caused by mutations in the genes: ELN, ATP6V0A2,ATP7A, FBLN4, FBLN5, and PYCR1. A related neurocutaneous syndrome may be caused by mutations in the gene ALDH18A1 (P5CS). Cutis laxa may also be seen in association with inherited connective tissue disorders such as Ehlers–Danlos syndromes </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 Primary cutaneous coccidioidomycosis and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Sonoda syndrome and can you explain it in depth? [/INST] Sonoda syndrome is a rare genetic disorder characterized by cranio-facial dysmorphisms, fingerprint abnormalities, intellectual disability, and congenital cardiopathy. It has been described in a Japanese family.

History
This condition has only been described once in history in three siblings from Japan (1987).This trio of siblings was born in Miyazaki Prefecture, Japan to healthy, non-consanguineous Japanese parents who were in their mid-20s (25 years old, to be exact). The parents height (the father was 170 cm tall and the mother was 153 cm tall), skin color (light), and craniofacial appearance were normal and average for their Japanese background, the mother did not have any history of miscarriage or stillbirth. While the both of them denied parental consanguinity, both of their familial lineages had lived in the same small isolated village for various years.The proband was a 6-year-old toddler girl, she was born weighing 2664 grams. Measurements taken in March 1983 (nearly 2 years after her birth) showed a height of 73.1 cm, a weight of 7.1 kg, and a head circumference of 46 cm. Physical examination done in 87 detailed her dark skin tone and light brown hair (which the authors described as uncommon among the Japanese), a round face, flat nasal bridge, small nose, nostril anteversion, and the presence of whorls and loops in her fingerprints (3 and 7, respectively). Routine laboratory tests and a 550-band level karyotype gave normal results. She was noted to have a heart murmur which was then discovered to be caused by a ventricular septal defect (a type of congenital heart defect), but it disappeared on its own few years after the physical examination that discovered said defect (thought to be caused by a spontaneous closure of said defect).The second case was her younger, 4-year-old toddler brother. He was born weighing 3042 grams, and was noted to have cyanosis at birth, which was an indicator for a possible heart anomaly. He learned how to control his head at 3 months of age and learned how to walk when he was 20 months old, at the age of 2 he was found to have a speech delay and could only say a handful of words. Physical examination done on him in July 1984 showed a height of 72.7 cm, a weight of 7.7 km, and a head circumference of 44.5 cm. He had the same skin tone, hair color, and facial characteristics as his proband sister. A systolic ejection murmur (grade 4/6) could be heard at his second left intercostal face, this same murmur was later discovered to be caused by pulmonary valve stenosis. Like his sister, he also had whorls and loops in his fingerprints (4 and 6, respectively), and he had routine laboratory tests and a karyotype which turned back normal. Physical examination done in him again in May 1987 showed a height of 94.3 cm, a weight of 45.2 kg, and a head circumference of 49.7 cm. His bone age was appropriate for his age.The third and final case was the youngest brother of the three, a 2-year old infant boy </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 Classic autism and can you explain it in depth? [/INST] Kanner autism, or classic autism, is an outdated neurodevelopmental diagnosis which is now considered part of autism spectrum disorder. The term autism was historically used to refer specifically to classic autism, but it is now more commonly used for the spectrum at large.Parents often noticed signs of autism during the first three years of their childs life.Autism was hypothesized to be caused by a combination of genetic and environmental factors, with genetic factors thought to heavily predominate. Controversies surround other proposed environmental causes; for example, the vaccine hypothesis, which although disproven, continues to hold sway in certain communities. Contemporary diagnostic manuals include only one diagnosis - autism spectrum disorder (ASD) - which includes classic autism along with Asperger syndrome and pervasive developmental disorder not otherwise specified (PDD-NOS).Globally, classic autism was estimated to affect 24.8 million people as of 2015.

Characteristics
Classic autism is a highly variable neurodevelopmental disorder whose symptoms first appear during infancy or childhood, and generally follows a steady course without remission. Autistic people may be severely impaired in some respects but average, or even superior, in others. Overt symptoms gradually begin after the age of six months and become established by age two or three years. Some autistic children experience regression in their communication and social skills after reaching developmental milestones at a normal pace.
It was said to be distinguished by a characteristic triad of symptoms: impairments in social interaction, impairments in communication, and repetitive behavior. Other aspects, such as atypical eating, are also common but are not essential for diagnosis. Individual symptoms of autism occur in the general population and appear not to associate highly, without a sharp line separating pathologically severe from common traits.

Social development
Autistic people have social impairments and often lack the intuition about others that many people take for granted. Unusual social development becomes apparent early in childhood. Autistic infants show less attention to social stimuli, smile and look at others less often, and respond less to their own name. Autistic toddlers differ more strikingly from social norms; for example, they have less eye contact and turn-taking, and do not have the ability to use simple movements to express themselves, such as pointing at things. Three- to five-year-old autistic children are less likely to exhibit social understanding, approach others spontaneously, imitate and respond to emotions, communicate nonverbally, and take turns with others. However, they do form attachments to their primary caregivers. Most autistic children displayed moderately less attachment security than neurotypical children, although this difference disappears in children with higher mental development or less pronounced autistic traits. Children with high-functioning autism have more intense and frequent loneliness compared to non-autistic peers, despite the common belief that autistic children prefer to be alone. Making and maintaining friendships often proves to be difficult for autistic people. For them, the quality of friendships, not the number of friends, predicts how lonely they feel. Functional friendships, such as those resulting in invitations to parties, may affect the quality of life more deeply.

Communication
Differences in communication may be present from the first year of life, and may include delayed onset of babbling, unusual gestures, diminished responsiveness, and vocal patterns that are not synchronized with the caregiver. In the second and third years, autistic children have less frequent and less diverse babbling, consonants, words, and word combinations; their gestures are less often integrated with words. Autistic children are less likely to make requests or share experiences, and are more likely to simply repeat others words (echolalia) or reverse pronouns. Deficits in joint attention may be present - for example, they may look at a pointing hand instead of the object to which the hand is pointing. Autistic children may have difficulty with imaginative play and with developing symbols into language.

Repetitive behavior
Autistic individuals can display many forms of repetitive or restricted behavior, which the Repetitive Behavior Scale-Revised (RBS-R) categorizes as follows.
Stereotyped behaviors: Repetitive movements, such as hand flapping, head rolling, or body rocking.
Compulsive behaviors: Time-consuming behaviors intended to reduce the anxiety that an individual feels compelled to perform repeatedly or according to rigid rules, such as placing objects in a specific order, checking things, or handwashing.
Sameness: Resistance to change; for example, insisting that the furniture not be moved or refusing to be interrupted.
Ritualistic behavior: Unvarying pattern of daily activities, such as an unchanging menu or a dressing ritual.
Restricted interests: Interests or fixations that are abnormal in theme or intensity of focus, such as preoccupation with a single television program, toy, or game.No single repetitive or self-injurious behavior seems to be specific to autism, but autism appears to have an elevated pattern of occurrence and severity of these behaviors.

Other symptoms
Autistic individuals may have symptoms that are independent of the diagnosis. An estimated 0.5% to 10% of individuals with classic autism show unusual abilities, ranging from splinter skills such as the memorization of trivia to the extraordinarily rare talents of prodigious autistic savants. Sensory abnormalities are found in over 90% of autistic people, and are considered core features by some, although there was no good evidence that sensory symptoms differentiate autism from other developmental disorders. An estimated 60–80% of autistic people have motor signs that include poor muscle tone, poor motor planning, and toe walking.

Causes
It was presumed initially that there was a common cause at the genetic, cognitive, and neural levels for classic autisms characteristic triad of symptoms. However, over time, there was increasing evidence that autism was instead a complex and highly heritable disorder whose core aspects have distinct causes which often often co-occur.

Although theories regarding vaccines lack convincing scientific evidence, are biologically implausible, and originated from a fraudulent study, parental concern about a potential vaccine link with autism (and subsequent concern about ASD) has led to lower rates of childhood immunizations, outbreaks of previously controlled childhood diseases in some countries, and the preventable deaths of several children.

Diagnosis
Diagnosis of classic autism was based on behavioral symptoms, not cause or mechanism.

Classification
Classic autism was listed as autistic disorder in the fourth edition of the American Psychiatric Associations diagnostic manual, as one of the five pervasive developmental disorders (PDDs). However, the PDDs were collapsed into the single diagnosis of Autism Spectrum Disorder in 2013, and the WHOs diagnostic manual ICD-11 (which had listed it as childhood autism in its previous edition) followed suit a few years later. Classic autism was said to be characterized by widespread abnormalities of social interactions and communication, severely restricted interests, and highly repetitive behavior.Of the PDDs, Asperger syndrome was closest to classic autism in signs and likely causes; Rett syndrome and childhood disintegrative disorder share several signs with it, but were understood to potentially have unrelated causes; PDD not otherwise specified (PDD-NOS; also called atypical autism) was diagnosed when the criteria are not met for one of the other four PDDs. People would usually attract a diagnosis of Asperger syndrome rather than classic autism if they showed no substantial delay in language development, but early language ability was found to be a poor predictor of outcomes in adulthood.

Prognosis and management
There is no known cure for autism, and very little research addressed long-term prognosis for classic autism. Many autistic children lack social support, future employment opportunities or self-determination.The main goals when treating autistic children are to lessen associated deficits and family distress, and to increase quality of life and functional independence. In general, higher IQs are correlated with greater responsiveness to treatment and improved treatment outcomes. Services should be carried out by behavior analysts, special education teachers, speech pathologists, and licensed psychologists.
Intensive, sustained special education programs and behavior therapy early in life often improves functioning and decreases symptom severity and maladaptive behaviors; claims that intervention by around age three years is crucial are not substantiated.No known medication relieves autisms core symptoms of social and communication impairments.

Education
Early, intensive ABA therapy has demonstrated effectiveness in enhancing communication and adaptive functioning in preschool children; it is also well-established for improving the intellectual performance of that age group. It is not known whether treatment programs for children lead to significant improvements after the children grow up, and the limited research on the effectiveness of adult residential programs shows mixed results.

Alternative medicine
Although many alternative therapies and interventions were used, few are supported by scientific studies. Treatment approaches have little empirical support in quality-of-life contexts, and many programs focus on success measures that lack predictive validity and real-world relevance. Some alternative treatments placed autistic individuals at risk. For example, in 2005, a five-year-old child with autism was killed by botched chelation therapy (which is not recommended for autism as risks outweigh any potential benefits).

Epidemiology
Globally, classic autism was understood to affect an estimated 24.8 million people as of 2015. After it was recognised as a distinct disorder, reports of autism cases substantially increased, which was largely attributable to changes in diagnostic practices, referral patterns, availability of services, age at diagnosis, and public awareness (particularly among women).Several other conditions were commonly seen in children with autism. They include:

Intellectual disability. The percentage of autistic individuals who also met criteria for intellectual disability has been reported as anywhere from 25% to 70%, a wide variation illustrating the difficulty of assessing intelligence of individuals on the autism spectrum. In comparison, for PDD-NOS the association with intellectual disability was much weaker, and by definition, the diagnosis of Aspergers excluded intellectual disability.
Minor physical anomalies are significantly increased in the autistic population.
Preempted diagnoses. Although the DSM-IV ruled out the concurrent diagnosis of many other conditions along with autism, the full criteria for Attention deficit hyperactivity disorder (ADHD), Tourette syndrome, and other of these conditions were often present </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 Transient erythroblastopenia of childhood and can you explain it in depth? [/INST]  </s>


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hamartoma and can you explain it in depth? [/INST] A hamartoma is a mostly benign, local malformation of cells that resembles a neoplasm of local tissue but is usually due to an overgrowth of multiple aberrant cells, with a basis in a systemic genetic condition, rather than a growth descended from a single mutated cell (monoclonality), as would typically define a benign neoplasm/tumor. Despite this, many hamartomas are found to have clonal chromosomal aberrations that are acquired through somatic mutations, and on this basis the term hamartoma is sometimes considered synonymous with neoplasm. Hamartomas are by definition benign, slow-growing or self-limiting, though the underlying condition may still predispose the individual towards malignancies.
Hamartomas are usually caused by a genetic syndrome that affects the development cycle of all or at least multiple cells. Many of these conditions are classified as overgrowth syndromes or cancer syndromes. Hamartomas occur in many different parts of the body and are most often asymptomatic incidentalomas (undetected until they are found incidentally on an imaging study obtained for another reason). Additionally, the definition of hamartoma versus benign neoplasm is often unclear, since both lesions can be clonal. Lesions such as adenomas, developmental cysts, hemangiomas, lymphangiomas and rhabdomyomas within the kidneys, lungs or pancreas are interpreted by some experts as hamartomas while others consider them true neoplasms. Moreover, even though hamartomas show a benign histology, there is a risk of some rare but life-threatening complications such as those found in neurofibromatosis type I and tuberous sclerosis.It is different from choristoma, a closely related form of heterotopia. The two can be differentiated as follows: a hamartoma is an excess of normal tissue in a normal situation (e.g., a birthmark on the skin), while a choristoma is an excess of tissue in an abnormal situation (e.g., pancreatic tissue in the duodenum). The term hamartoma is from the Greek ἁμαρτία, hamartia ("error"), and was introduced by D.P.G. Albrecht in 1904.

Causes
Hamartomas result from an abnormal formation of normal tissue, although the underlying reasons for the abnormality are not fully understood. They grow along with, and at the same rate as, the organ from whose tissue they are made, and, unlike cancerous tumors, only rarely invade or compress surrounding structures significantly.

Diagnosis
Types
Lung
About 5–8% of all solitary lung nodules and about 75% of all benign lung tumors, are hamartomas. They almost always arise from connective tissue and are generally formed of cartilage, connective tissue, and fat cells, although they may include many other types of cells. The great majority of them form in the connective tissue on the outside of the lungs, although about 10% form deep in the linings of the bronchi. They can be worrisome, especially if situated deep in the lung, as it is sometimes difficult to make the important distinction between a hamartoma and a lung malignancy. An X-ray will often not provide a definitive diagnosis, and even a CT scan may be insufficient if the hamartoma lacks the typical cartilage and fat cells. Lung hamartomas may have popcorn-like calcifications on chest xray or computed tomography (CT scan).
Lung hamartomas are more common in men than in women, and may present additional difficulties in smokers.
Some lung hamartomas can compress surrounding lung tissue to a degree, but this is generally not debilitating and is often asymptomatic, especially for the more common peripheral growths. They are treated, if at all, by surgical resection, with an excellent prognosis: generally, the only real danger is the inherent possibility of surgical complications.

Heart
Cardiac rhabdomyomas are hamartomas composed of altered cardiac myocytes that contain large vacuoles and glycogen. They are the most common tumor of the heart in children and infants. There is a strong association between cardiac rhabdomyomas and tuberous sclerosis (characterized by hamartomas of the central nervous system, kidneys, and skin, as well as pancreatic cysts); 25-50% of patients with cardiac rhabdomyomas will have tuberous sclerosis, and up to 100% of patients with tuberous sclerosis will have cardiac masses by echocardiography. Symptoms depend on the size of the tumor, its location relative to the conduction system, and whether or not it obstructs blood flow. Symptoms are usually from congestive heart failure; in utero heart failure may occur. If patients survive infancy, their tumors may regress spontaneously; resection in symptomatic patients has good results.
Nerves
Sometimes nerves can also be affected. The most common nerve to be affected by hamartoma is reported to be median nerve.

Hypothalamus
One of the most troublesome hamartomas occurs on the hypothalamus. Unlike most such growths, a hypothalamic hamartoma is symptomatic; it most often causes gelastic seizures, and can cause visual problems, other seizures, rage disorders associated with hypothalamic diseases, and early onset of puberty. The symptoms typically begin in early infancy and are progressive, often into general cognitive and/or functional disability. Moreover, resection is usually difficult, as the growths are generally adjacent to, or even intertwined with, the optic nerve. Symptoms tend to be resistant to medical control; however, surgical techniques are improving and can result in immense improvement of prognosis.

Kidneys, stomach, spleen and other vascular organs
One general danger of hamartomas is that they may impinge into blood vessels, resulting in a risk of serious bleeding. Because a hamartoma typically lacks elastic tissue, it may lead to the formation of aneurysms and thus possible hemorrhage. Where a hamartoma impinges into a major blood vessel, such as the renal artery, hemorrhage must be considered life-threatening.
Angiomyolipoma of the kidney was previously considered to be a hamartoma or choristoma.
A myoepithelial hamartoma, also known as a pancreatic rest, is ectopic pancreatic tissue found in the stomach, duodenum, or proximal jejunum. When seen on upper gastrointestinal series, a pancreatic rest may appear to be a submucosal mass or gastric neoplasm. Most are asymptomatic, but they can cause dyspepsia or upper gastrointestinal bleeding.A hamartoma has been identified as a cause of partial outflow obstruction in the abomasum (true gastric stomach) of a dairy goat.Hamartomas of the spleen are uncommon but can be dangerous. About 50% of such cases manifest abdominal pain, and they are often associated with hematologic abnormalities and spontaneous rupture.

Cowden syndrome
Cowden syndrome is a serious genetic disorder characterized by multiple hamartomas. Usually skin hamartomas exist, and commonly (in about 66% of cases) hamartoma of the thyroid gland exists. Additional growths can form in many parts of the body, especially in bones, CNS, the eyes, the genitourinary tract, the GI tract, and mucosa. The hamartomas themselves may cause symptoms or even death, but morbidity is more often associated with increased occurrence of malignancies, usually in the breast or thyroid. Cowden syndrome is considered a PTEN hamartoma tumor syndrome (PHTS), which also includes Bannayan–Riley–Ruvalcaba syndrome, Proteus syndrome and Proteus-like syndrome.

Prognosis
Hamartomas, while generally benign, can cause problems due to their location </s>