Xq27.3-q28 duplication involving the FMR1 gene presenting with familial X-linked hypogonadism, gynecomastia, short stature, intellectual disability, and obesity syndrome: a case report and review of the literature.

OBJECTIVES: Duplications involving the Fragile X Mental Retardation 1 (FMR1) gene at Xq27.3-q28 underlie a rare but clinically distinctive genetic syndrome. This report aims to describe the clinical features of a pediatric male patient presenting with morbid obesity, hypogonadism, gynecomastia, short stature, and neurodevelopmental disorders, and to compare the findings with previously reported cases.

CASE PRESENTATION: A 17-year-old male presented to our clinic for obesity. He was followed by a child psychiatrist with diagnoses of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and moderate intellectual disability. Physical examination showed morbid obesity, bilateral gynecomastia, and reduced testicular volume. Endocrine evaluation demonstrated hypergonadotropic hypogonadism. Genetic testing identified a 5.5 Mb interstitial duplication at Xq27.3-q28 involving FMR1, inherited from his mother.

CONCLUSIONS: This patient represents the youngest living individual with a familial Xq27.3-q28 duplication reported to date. The syndrome resulting from FMR1 gene overdosage is characterized by combined neurodevelopmental and endocrine/metabolic abnormalities. FMR1 duplications should be considered in the differential diagnosis of pediatric patients presenting with similar clinical features.