XYYY syndrome, also known as 48,XYYY, is a chromosomal anomaly in which a man has two extra copies of the Y chromosome. The syndrome is exceptionally rare, with only twelve cases reported. The syndrome's phenotype is heterogeneous, but appears to be more severe than its counterpart, the XYY syndrome. Common traits include mild intellectual disability, infertility, radioulnar synostosis, and, in some cases, tall stature.
The presentation of the XYYY syndrome is variable and, since its first diagnosis to a boy in 1965, it is not entirely clear. As all known cases were diagnosed postnatally (after birth), and it is noticeable that XYY syndrome has a milder phenotype in prenatal cases than in cases diagnosed after birth, it is suspected that many cases of syndrome XYYY may be mild or asymptomatic. The intellectual capabilities of known XYYY cases have varied, especially in cases with mosaicism, but in most cases they are at the limit of intellectual functioning. Performance IQ is often higher than verbal IQ. Mild speech delays have been reported. Basic self-care skills, such as bathroom hygiene, dressing, feeding and hygiene, are normal or, at most, slightly delayed. Several minor skeletal anomalies are seen, such as clinodactyly, radioulnar synostosis (the fusion of the long bones in the forearm), and poor dental development. These findings are also seen in other sex chromosomal aneuploidies. Height is normal to tall, with some cases of unusually tall stature. Aside from severe teenage acne, XYYY syndrome is not associated with any obvious physical or facial abnormalities.
Since very few cases of XYYY syndrome in adult men have been reported, drawing certain conclusions about sexual functioning and reproduction is difficult. However, low testosterone appears to be associated. All adult males with a 48,XYYY non-mosaic karyotype known to the medical literature have been azoospermics, although one male reported with a 46,XY/48,XYYY mosaic complement (81.1% 48,XYYY) had some evidence of spermatogenesis. Some adults had impulsive or aggressive sexual behavior, while some had a low sex drive and no apparent sexual interest; one had gender dysphoria. Two men with XYYY syndrome are known to lead an independent adult life, getting married and finding a job, and only came to medical care for infertility. Behavioral issues, of varying severity, are associated with the syndrome. Some patients were transferred to special schools, high security group homes or institutions due to severe assault. However, those cases with particularly severe behavior problems were generally of problematic or abusive family background. While some descriptions of the syndrome emphasize aggression as a feature, most reports from parents of a charity with chromosomal disorders emphasize insecurity, immaturity, and shyness. Although teens with XYYY syndrome may be at-risk students, they are able to form a positive identity, and case reports after XYYY teens form their identity and personal development demonstrate a desire to have healthy relationships and successfully integrate in society.
XYYY syndrome is caused by two extra copies of the Y chromosome, the chromosome that determines male sexual development. Sex chromosomal aneuploidies are the most frequent causes of aneuploidy in humans. Although a complement of 48 chromosomes involving the autosomes was unbearable, 48,XYYY and other high-level sex chromosome aneuploidies such as s�