49,XXXXY syndrome

49,XXXXY syndrome is a chromosomal condition that causes intellectual disabilities, developmental delays, changes in sex characteristics and other physical features, and an inability to have biological children (infertility). Some of these signs and symptoms vary among affected individuals. 

People with 49,XXXXY syndrome have mild or moderate intellectual disabilities with learning difficulties. Speech and language development are particularly affected. Most affected individuals are better at understanding what other people say (receptive language) than producing speech (expressive language). Because many individuals with 49,XXXXY have difficulty making the mouth movements needed to speak, they are often diagnosed with a condition called childhood apraxia of speech.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. Some people with 49,XXXXY have involuntary tensing of the neck, which causes the head to tilt or turn (torticollis).Affected infants and children are often shorter than their peers, but some catch up in height later in childhood or adolescence.

The physical differences that are associated with 49,XXXXY syndrome include the fusion of bones in the forearm (radioulnar synostosis), an unusually large range of joint movement (hyperextensibility), elbow abnormalities, curved pinky fingers (fifth finger clinodactyly), and flat feet (pes planus). Affected individuals have distinctive facial features that can include widely spaced eyes (ocular hypertelorism), an upward tilt to the outside corners of the eyes (upslanting palpebral fissures), skin folds that cover the inner corner of the eyes (epicanthal folds), and a flat bridge of the nose. Dental abnormalities are also common in people with 49,XXXXY syndrome.

49,XXXXY syndrome disrupts the development of typically male sex characteristics. The penis is often short and underdeveloped, and the testes may be undescended, which means they are located inside the pelvis or abdomen instead of outside of the body. The testes are small and do not produce sperm, so all individuals with 49,XXXXY syndrome are infertile. 49,XXXXY syndrome reduces the production of testosterone, which is the hormone that directs male sexual development. Without treatment, the shortage of testosterone often leads to incomplete puberty. Starting in adolescence, affected individuals may have sparse body hair, and some experience breast enlargement (gynecomastia).