Prostate Restored
Prostate Restored
Photo: Yan Krukov
48, XXYY syndrome has previously been described as a variant of Klinefelter syndrome because affected males have similar physical characteristics (tall stature and small, dysfunctional testes), however the medical and neurodevelopmental features are more complex than typically seen in 47, XXY/Klinefelter syndrome.
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Read More »In infancy and early childhood, delayed milestones in speech and motor skills are common, as are medical features including low muscle tone (hypotonia), feeding disorders, delayed appearance of teeth, crossed eyes (strabismus) and a twisted neck (torticollis) with flattening on one side of the head. Other physical features can include a skin fold of the upper eyelid covering the inner corner of the eye (epicanthal fold), an abnormally large distance between the eyes (hypertelorism) and an abnormally bend or curved 5th finger (clinodactyly). There are also increased risks for congenital heart defects, kidney malformations and skeletal abnormalities including pes planus, club foot, radioulnar synostosis, cubitus varus (with prominent elbows), scoliosis and kyphosis. Other medical conditions that are more frequent in 48, XXYY syndrome include epilepsy (~15%), tremor (~60% of adults), asthma/allergies (~60%), significant dental problems (~90%), gastrointestinal problems (feeding intolerance, reflux, constipation, eosinophilic esophagitis), joint laxity, sleep apnea, thrombosis (~18%) and type 2 diabetes (~20% in adulthood). Tall stature is another common physical feature that can be more noticeable in adolescence. Small testes (microorchidism) and resulting testicular dysfunction leads to hypergonadotropic hypogonadism (low testosterone levels) that is nearly universal which starts in adolescence and persists throughout the lifetime. Low testosterone levels can be associated with incomplete pubertal development (decreased development of facial and body hair), decreased muscle bulk and strength, fatigue, low endurance and mental health effects such as depression. Testicular dysfunction is also associated with impaired fertility. Undescended testes (cryptorchidism), inguinal hernias, micropenis, and enlargement of breast tissue (gynecomastia) can also be associated, however gynecomastia can be prevented or minimized with appropriate testosterone management starting in adolescence. 48, XXYY syndrome presents with more significant cognitive impairments and behavior challenges compared to 47, XXY. Developmental delays are often present in the first 3 years of life in the areas of speech and motor development. Overall cognitive abilities tend to be in the borderline range (IQ of 70 – 80) with approximately 1/3 of males with 48, XXYY with full scale IQ in the intellectual disability range (<70). Cognitive profiles often show significantly lower verbal reasoning skills compared to nonverbal and visual-spatial skills (which are often areas of strength). Language disorders and learning disabilities (especially with reading) are very common. Adaptive functioning (life skills) also commonly show deficits in communication, social skills, self-care and self-direction. Motor coordination deficits are also common. Behavioral characteristics can include executive function impairments, difficulties with attention, impulsivity and hyperactivity. Attention-deficit/hyperactivity disorder (ADHD) is often diagnosed. Mood instability, short frustration tolerance, anxiety, compulsive behaviors and emotional immaturity are also characteristic of 48, XXYY. Additional features can include nail biting, sugar cravings and intense interests. There is increased risk for social difficulties, including difficulties in social skills, reciprocal social interactions and insight into social relationships. As a result, there is an increased risk for an autism spectrum disorder (ASD) diagnosis, and approximately half of males with 48, XXYY met DSM-5 criteria for ASD in a research study. Common strengths include artistic skills, computer skills and navigation skills.
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