Синдром 47,XYY: особенности и проявления

Genetic condition in which a male has an extra Y chromosome

People with the 47,XYY karyotype have an increased growth rate from early childhood, with an average final height approximately above expected final height. In Edinburgh, Scotland, eight 47,XYY boys born 1967–1972 and identified in a newborn screening programme had an average height of at age 18—their fathers' average height was , their mothers' average height was The increased gene dosage of three X/Y chromosome pseudoautosomal region (PAR1) SHOX genes has been postulated as a cause of the increased stature seen in all three sex chromosome trisomies: 47,XXX, 47,XXY, and 47,XYY. Severe acne was noted in a very few early case reports, but dermatologists specializing in acne now doubt the existence of a relationship with 47,XYY. Prenatal testosterone levels are normal in 47,XYY males. Most 47,XYY males have normal sexual development and have normal fertility.

In contrast to the other common sex chromosome aneuploidies—47,XXX and 47,XXY (Klinefelter syndrome)—the average of the IQ scores of 47,XYY boys identified by newborn screening programs was not reduced compared to the general population. In a summary of six prospective studies of 47,XYY boys identified by newborn screening programmes, twenty eight 47,XYY boys had an average 100.76 verbal IQ, 108.79 performance IQ, and 105.00 full scale IQ. In a systematic review including two prospective studies of 47,XYY boys identified by newborn screening programs and one retrospective study of 47,XYY men identified by screening men over in height, forty two 47,XYY boys and men had an average 99.5 verbal IQ and 106.4 performance IQ. In prospective studies of 47,XYY boys identified by newborn screening programs, the IQ scores of 47,XYY boys were usually slightly lower than those of their siblings. In Edinburgh, fifteen 47,XYY boys with siblings identified in a newborn screening program had an average 104.0 verbal IQ and 106.7 performance IQ, while their siblings had an average 112.9 verbal IQ and 114.6 performance IQ. These men could be diagnosed with infertility as a result of oligospermia or sperm chromosomal abnormalities. In some cases, the extra Y chromosome results from nondisjunction during mitosis in early embryonic development. This can produce 46,XY/47,XYY mosaics. in order to obtain a chromosome karyotype, where the abnormality can be observed. It is estimated that only 15–20% of children with 47,XYY syndrome are ever diagnosed. Of these, approximately 30% are diagnosed prenatally. For the rest of those diagnosed after birth, around half are diagnosed during childhood or adolescence after developmental delays are observed. The rest are diagnosed after any of a variety of symptoms, including fertility problems (5%) have been seen.

Around 1 in 1,000 boys are born with a 47,XYY karyotype. In the wake of the establishment of the normal number of human chromosomes, 47,XYY was the last of the common sex chromosome aneuploidies to be discovered, two years after the discoveries of 47,XXY, 45,X and 47,XXX in 1959. Even the much less common 48,XXYY had been discovered in 1960, a year before 47,XYY. Screening for those X chromosome aneuploidies was possible before the advent of human chromosome analysis by noting the presence or absence of "female" sex chromatin bodies (Barr bodies) in the nuclei of interphase cells in buccal smears, a technique developed a decade before the first reported sex chromosome aneuploidy. An analogous technique to screen for Y chromosome aneuploidies by noting supernumerary "male" sex chromatin bodies was not developed until 1970, a decade after the first reported male sex chromosome aneuploidy. The first published report of a man with a 47,XYY karyotype was by the American cytogeneticist Avery Sandberg and his colleagues at Roswell Park Comprehensive Cancer Center (then known as Roswell Park Memorial Institute) in Buffalo, New York in 1961. It was an incidental finding in a normal 44 year old, 6 ft. [183 cm] tall man of average intelligence who was karyotyped because he had a daughter with Down syndrome. Only a dozen isolated 47,XYY cases were reported in the medical literature in the four years following the first report by Sandberg. The XYY syndrome, if named after the discoverer, should rightly be termed Sandberg syndrome and not Jacobs syndrome although the British cytogeneticist Patricia Jacobs did indeed contribute meaningly to our knowledge of XYY. In December 1965 and March 1966, Nature and The Lancet published the first preliminary reports by Jacobs and her colleagues at the MRC Human Genetics Unit at Western General Hospital in Edinburgh of a chromosome survey of 315 male patients at State Hospital in Carstairs, Lanarkshire—Scotland's only special security hospital for developmentally disabled people —that found nine patients, ages 17 to 36, averaging almost 6 ft. in height (avg. 5'11", range: 5'7" to 6'2"), had a 47,XYY karyotype, and mischaracterized them as aggressive and violent criminals. Over the next decade, almost all published XYY studies were on height selected, institutionalized XYY males. Telfer found five tall, developmentally disabled XYY boys and men in hospitals and penal institutions in Pennsylvania, and since four of the five had at least moderate facial acne, reached the erroneous conclusion that acne was a defining characteristic of XYY males. In April 1968, The New York Times—using Telfer as a main source—introduced the XYY genetic condition to the general public in a three part series on consecutive days that began with a Sunday front page story about the planned use of the condition as a mitigating factor in two murder trials in Paris and Melbourne—and falsely reported that Richard Speck was an XYY male and that the condition would be used in an appeal of his murder conviction. The series was echoed the following week by articles—again using Telfer as a main source—in Time and Newsweek, and six months later in The New York Times Magazine. In December 1968, the Journal of Medical Genetics published the first XYY review article—by Willam Michael Court Brown (1918–1969), director of the MRC Human Genetics Unit—which reported that he had found no overrepresentation of XYY males in nationwide chromosome surveys of prisons and hospitals for developmentally disabled and mentally ill people in Scotland, and concluded that studies confined to institutionalized XYY males may be guilty of selection bias, and that long term longitudinal prospective studies of newborn XYY boys were needed. In June 1969, the National Institute of Mental Health (NIMH) Center for Studies of Crime and Delinquency held a two day XYY conference in Chevy Chase, Maryland. In December 1969, with a grant from the NIMH Center for Studies of Crime and Delinquency, cytogeneticist Digamber Borgaonkar at Johns Hopkins Hospital began a chromosome survey of (predominantly African American) boys ages 8 to 18 in all Maryland institutions for delinquent, neglected, or mentally ill juveniles, which was suspended from February–May 1970 due to an American Civil Liberties Union (ACLU) lawsuit regarding the study's lack of informed consent. In the late 1960s and early 1970s, screening of consecutive newborns for sex chromosome abnormalities was undertaken at seven centers worldwide: in Denver (Jan 1964–1974), Edinburgh (Apr 1967–Jun 1979), New Haven (Oct 1967–Sep 1968), Toronto (Oct 1967–Sep 1971), Aarhus (Oct 1969–Jan 1974, Oct 1980–Jan 1989), Winnipeg (Feb 1970–Sep 1973), and Boston (Apr 1970–Nov 1974). The Boston study, led by Harvard Medical School child psychiatrist Stanley Walzer at Children's Hospital, was unique among the seven newborn screening studies in that it only screened newborn boys (non private ward newborn boys at the Boston Hospital for Women) and was funded in part by grants from the NIMH Center for Studies of Crime and Delinquency. The Edinburgh study was led by Shirley Ratcliffe who focused her career on it and published the results in 1999.

In December 1969, Lore Zech at the Karolinska Institute in Stockholm first reported intense fluorescence of the A T rich distal half of the long arm of the Y chromosome in the nuclei of metaphase cells treated with quinacrine mustard. In April 1970, Peter Pearson and Martin Bobrow at the MRC Population Genetics Unit in Oxford and Canino Vosa at the University of Oxford reported fluorescent "male" sex chromatin bodies in the nuclei of interphase cells in buccal smears treated with quinacrine dihydrochloride, which could be used to screen for Y chromosome aneuploidies like 47,XYY. In December 1970, at the annual meeting of the American Association for the Advancement of Science (AAAS), its retiring president, geneticist H. Bentley Glass, cheered by the legalization of abortion in New York, envisioned a future where pregnant women would be required by the government to abort XYY "sex deviants". Mischaracterization of the XYY genetic condition was quickly incorporated into high school biology textbooks and medical school psychiatry textbooks, where misinformation still persists decades later. In August 1976, Science published a retrospective cohort study by Educational Testing Service psychologist Herman Witkin and colleagues that screened the tallest 16% of men (over 184 cm (6'0") in height) born in Copenhagen from 1944 to 1947 for XXY and XYY karyotypes, and found an increased rate of minor criminal convictions for property crimes among sixteen XXY and twelve XYY men may be related to the lower intelligence of those with criminal convictions, but found no evidence that XXY or XYY men were inclined to be aggressive or violent.

The March of Dimes sponsored five international conferences in June 1974, November 1977, May 1981, June 1984, and June 1989 and published articles from the conferences in book form in 1979, 1982, 1986, and 1991 from seven longitudinal prospective cohort studies on the development of over 300 children and young adults with sex chromosome abnormalities identified in the screening of almost 200,000 consecutive births in hospitals in Denver, Edinburgh, New Haven, Toronto, Aarhus, Winnipeg, and Boston from 1964 to 1975. These seven studies—the only unbiased studies of unselected individuals with sex chromosome abnormalities—have replaced the older, biased studies of institutionalized individuals in understanding the development of individuals with sex chromosome abnormalities. In May 1997, Nature Genetics published the discovery by Ercole Rao and colleagues of the X/Y chromosome pseudoautosomal region (PAR1) SHOX gene, haploinsufficiency of which leads to short stature in Turner syndrome (45,X). It was subsequently postulated that the increased gene dosage of three SHOX genes leads to tall stature in the sex chromosome trisomies 47,XXX, 47,XXY, and 47,XYY. In June 2002, the American Journal of Medical Genetics published results from a longitudinal prospective cohort Denver Family Development Study led by pediatrician and geneticist Arthur Robinson, which found that in fourteen prenatally diagnosed 47,XYY boys (from high socioeconomic status families), IQ scores available for six boys ranged from 100 to 147 with a mean of 120. For the eleven of fourteen boys with siblings, in nine instances their siblings were stronger academically, but in one case the subject was performing equal to, and in another case superior to, his siblings. because many people with this karyotype appear normal.

In June 1970, The XYY Man was published—the first of seven Kenneth Royce spy novels whose fictional tall, intelligent, nonviolent XYY hero was a reformed expert cat burglar recruited by British intelligence for dangerous assignments—and later adapted into a thirteen episode British summer television series broadcast in 1976 and 1977. In other fictional television works, a January 1971 episode "By the Pricking of My Thumbs " of the British science fiction TV series Doomwatch featured an XYY boy expelled from school because his genetic condition led him to be falsely accused of nearly blinding another boy. A November 1993 episode of the American police procedural TV series Law & Order, "Born Bad", portrays a 14 year old XYY sociopathic murderer. The May 2007 season finale episode, "Born To Kill", of the American police procedural TV series CSI: Miami depicts a 34 year old XYY serial killer. The false stereotype of XYY boys and men as violent criminals has also been used as a plot device in the horror films Il gatto a nove code in February 1971 (dubbed into English as The Cat o' Nine Tails in May 1971) and Alien 3 in May 1992.