XYY Syndrome

XYY syndrome (47,XYY) is a sex chromosome aneuploidy in males, with tall stature, learning and language difficulties, and increased risk of neurodevelopmental conditions, but normal fertility and normal sexual development. It affects about 1 in 1000 male births, and many men are never diagnosed.

Pathophysiology. The extra Y chromosome arises from paternal meiosis II non-disjunction. Extra copies of Y-linked and pseudoautosomal genes, particularly SHOX, influence growth and neurodevelopment.

Testosterone and gonadotropin levels are usually normal.

Earlier claims of excess aggression or criminality came from biased samples. Behaviour issues are better explained by ADHD, language and learning difficulties, and need support rather than stigma.

• Tall stature from childhood, with increased growth velocity
• Hypotonia, motor delay and tremor
• Speech and language delay, learning difficulties
• ADHD, autism spectrum disorder, anxiety, behavioural outbursts
• Macrocephaly, hypertelorism
• Severe acne in adolescence
• Normal puberty and fertility in most; rarely oligospermia
• Asthma, and increased dental and orthodontic needs
• Often no recognisable features

• Karyotype or chromosomal microarray showing 47,XYY (or mosaic form).
• Prenatal detection by cell free DNA screening or amniocentesis, confirmed by invasive testing.
• Developmental assessment: speech and language, cognitive testing, and motor assessment.
• Neuropsychiatric evaluation for ADHD and autism spectrum disorder when concerns arise.
• Endocrine evaluation: testosterone and gonadotropins if puberty is abnormal.
• Hearing and vision screening.

• Early intervention: speech and language therapy, occupational therapy, and physiotherapy for hypotonia and coordination.
• Education: individual education plans, early neuropsychological testing, and school based support.
• ADHD treatment: methylphenidate 5 mg orally once or twice daily increasing weekly by 5 to 10 mg to a usual maximum of 60 mg daily (up to 100 mg in adults under specialist care), with monitoring of growth, heart rate and blood pressure. Behavioural interventions are used alongside.
• Anxiety and mood: cognitive behavioural therapy, and sertraline 25 to 50 mg daily increasing to a maximum of 200 mg daily when drug therapy is needed.
• Acne: topical therapy, and isotretinoin 0.5 mg/kg daily increasing to 1 mg/kg daily for severe disease in specialist care.
• Reproductive health: counselling that fertility is usually normal, that children are almost always chromosomally normal, and semen analysis if difficulty conceiving.
• Counselling: explain the wide range of outcomes and the absence of a link to aggression or criminality.

Special groups.

• Prenatal diagnosis: balanced counselling on the wide range of outcomes and typical normal fertility.
• Adolescents: support for social skills, relationships and education.

Monitoring. Review growth, development, school progress and mental health every 6 to 12 months in childhood.

Referral and escalation. Refer to clinical genetics, developmental paediatrics and child psychiatry. Urgent for self-harm risk, severe behavioural crisis or developmental regression.