XYYYY syndrome

XYYYY syndrome, also known as 49,XYYYY, is an exceptionally rare chromosomal disorder in which a male human has three additional copies of the Y chromosome. Only seven non-mosaic cases of the disorder have ever been recorded in the medical literature, as well as five mosaic cases, of which two had more 48,XYYY than 49,XYYYY cells.^[1] Due to the extreme rarity of the disorder, little is understood about it,^[2] and the phenotype appears to be variable.^[3]

XYYYY syndrome is associated with developmental and skeletal anomalies that are also observed in other sex chromosome aneuploidies. Findings associated with the karyotype include hypertelorism (wide-spaced eyes), low-set ears, radioulnar synostosis (fusion of the long bones in the forearm), and clinodactyly (incurved pinky fingers).^[2] Intellectual disability has been observed in all cases old enough to test^[3] and is in the mild to moderate range.^{[1][note 1]} Though other Y-chromosome polysomy disorders are associated with tall stature,^[5] this does not appear to be true in XYYYY syndrome, with recorded heights ranging from the 10th to 97th percentile.^[3] Autism and attention-deficit hyperactivity disorder are both thought to be associated with the syndrome.^[1] External genitalia are normal, but testicular insufficiency appears to develop during childhood and lead to adult azoospermia.^[2]

Non-mosaic XYYYY syndrome was first recorded in 1981 in a 14-month-old boy, though a mosaic case with mixed 49,XYYYY and 45,X0 cells had been recorded in 1968.^[6] This case was followed up at the age of seven, providing the only known long-term follow-up of the disorder.^[3] Only two adults with XYYYY syndrome have been described.^[1]

The disorder's prevalence is estimated to be below 1 in 1,000,000.^[4]

• XYY syndrome
• XYYY syndrome