48,XXYY syndrome is a chromosomal condition that affects development in people who are assigned male at birth. There is a lot of variability in symptoms between people with 48,XXYY syndrome. Almost all affected individuals have developmental delays in infancy and develop decreased testosterone levels (hypogonadism) during adolescence. People with 48,XXYY syndrome are also at risk for other health problems.
Adolescents and adults with this condition usually have small testes that do not produce enough testosterone, which is the hormone that directs male sexual development. Without treatment, a shortage of testosterone during puberty can lead to reduced facial and body hair, poor muscle development, low energy levels, and an increased risk of breast enlargement (gynecomastia). Because their testes do not function normally, individuals with 48,XXYY syndrome have difficulty having biological children (a condition called infertility), but they may be able to have children using assisted reproductive technologies.
48,XXYY syndrome can affect other parts of the body as well. Affected individuals are often taller than their peers, with an average adult height of 6 feet, 4 inches (193 cm). They may develop a mild to moderate hand tremor that typically starts in adolescence and may increase with age. Dental problems are frequently seen in people with this condition, including delayed appearance of the primary (baby) or secondary (adult) teeth, thin tooth enamel, crowded or misaligned teeth, and multiple cavities.
Additionally, individuals with 48,XXYY syndrome may have flat feet (pes planus), elbow abnormalities, abnormal fusion of certain bones in the forearm (radioulnar synostosis), allergies, asthma, type 2 diabetes, seizures, congenital heart defects, and an inflammatory condition in the throat (esophagus) called eosinophilic esophagitis. As people with 48,XXYY get older, they may develop a narrowing of the blood vessels in the legs called peripheral vascular disease. Peripheral vascular disease can cause skin ulcers to form. Affected individuals are also at risk of developing a type of clot called a deep vein thrombosis that occurs in the deep veins of the legs.
Most individuals with 48,XXYY syndrome have an IQ score that ranges from 60 to 80 and have some degree of difficulty with speech and language development. The development of motor skills such as sitting, standing, and walking may be delayed in some children with 48,XXYY syndrome. They may also have poor coordination. Learning disabilities are very common in people with this disorder, especially in the areas of reading and written expression. People with 48,XXYY typically perform better at tasks focused on math, visual-spatial skills such as puzzles, and memorization of locations or directions. Affected individuals have higher-than-average rates of other neurodevelopmental and behavioral disorders, such as attention-deficit/hyperactivity disorder (ADHD); mood disorders, including anxiety and depression; and autism spectrum disorder, which affects communication and social interaction. [from
MedlinePlus Genetics]