49,XXXXY syndrome is a chromosomal condition in boys and men that causes intellectual disability, developmental delays, physical differences, and an inability to father biological children (infertility). Its signs and symptoms vary among affected individuals.
Boys and men with 49,XXXXY syndrome have mild or moderate intellectual disability with learning difficulties. Speech and language development is particularly affected. Most affected boys and men can understand what other people say more easily than they themselves can speak. People with 49,XXXXY syndrome tend to be shy and friendly, but problems with speech and communication can contribute to behavioral issues, including irritability, difficulty tolerating frustration, defiant behavior, and outbursts or temper tantrums.
49,XXXXY syndrome is also associated with weak muscle tone (hypotonia) and problems with coordination that delay the development of motor skills, such as sitting, standing, and walking. Affected infants and young boys are often shorter than their peers, but some catch up in height later in childhood or adolescence.
Other physical differences associated with 49,XXXXY syndrome include abnormal fusion of certain bones in the forearm (radioulnar synostosis), an unusually large range of joint movement (), elbow abnormalities, curved pinky fingers (fifth finger ), and flat feet (). Affected individuals have distinctive facial features that can include widely spaced eyes (), outside corners of the eyes that point upward (), skin folds covering the inner corner of the eyes (epicanthal folds), and a flat bridge of the nose. Dental abnormalities are also common in this disorder.
49,XXXXY syndrome disrupts male sexual development. The penis is often short and underdeveloped, and the testes may be undescended, which means they are abnormally located inside the pelvis or abdomen. The testes are small and do not produce enough testosterone, which is the hormone that directs male sexual development. The shortage of testosterone often leads to incomplete puberty. Starting in adolescence, affected boys and men may have sparse body hair, and some experience breast enlargement (gynecomastia). Their testes do not produce sperm, so all men with 49,XXXXY syndrome are infertile.