Rare 48, XXYY Syndrome with Primary Infertility and Behavioural Disorder: A Case Report

The syndrome, 48, XXYY is a rare sex chromosome aneuploidy in males. These individuals have unique clinical features such as male infertility, testicular agenesis, tall stature, gynaecomastia, tremors and variable phenotypes of neurodevelopment and psychiatric disorders. We report a case of a 32-yea...

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Main Authors: Prafulla S. Ambulkar, Shuchi Jain, Jwalant Waghmare, Pratibha Narang
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2025-04-01
Series:Journal of Human Reproductive Sciences
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Online Access:https://journals.lww.com/10.4103/jhrs.jhrs_43_25
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Summary:The syndrome, 48, XXYY is a rare sex chromosome aneuploidy in males. These individuals have unique clinical features such as male infertility, testicular agenesis, tall stature, gynaecomastia, tremors and variable phenotypes of neurodevelopment and psychiatric disorders. We report a case of a 32-year-old infertile male patient with tall stature and atrophied testes. The seminal analysis showed azoospermia. Hormone analysis and ultrasonographic evaluation confirmed the diagnosis as non-obstructive azoospermia. Clinically, he was diagnosed with Klinefelter syndrome (KS). Cytogenetic investigation confirmed an abnormal male karyotype with sex chromosome aneuploidy, with a 48, XXYY genotype. He had more complex physical, medical and psychological phenotypes which made him distinct from males with 47, XXY KS. Although hypergonadotropic hypogonadism features are shared in both syndromes, the 48, XXYY patients have more psychological disorders, with moderate intellectual disability and attention-deficit/hyperactivity disorders (ADHD). This patient had the rare 48, XXYY chromosomal constitution, which is considered a variant of KS but manifests with more complex clinical and psychological features. Most 48, XXYY males are diagnosed due to infertility. In addition to cognitive impairment and developmental delay, behavioural dysfunction and difficulties in occupational skills are the main complications. Early detection, clinical assessment, genetic counselling, hormonal therapy and infertility management are essential for better long-term outcomes for these patients.
ISSN:0974-1208
1998-4766