Case Report of 49,XXXXY Syndrome: A Rare Variation of Klinefelter Syndrome With Seizure Disorder and ASD.

This case report presents a rare occurrence of 49,XXXXY syndrome in a 14-month-old male, the first documented case from Nepal, highlighting several distinctive clinical features. The patient had a height and weight below the third centile at birth and exhibited dysmorphic facial features, including a flat facial profile, flat nasal bridge, broad nose, low-set ears, and clinodactyly, along with genital anomalies like micropenis and small testes. Neurologically, he demonstrated generalized hypotonia and global developmental delay. Atrial septal defect (ASD), left to right shunt, and mild tricuspid regurgitation were identified via echocardiography, adding to the complexity of the clinical presentation. Cytogenetic analysis of peripheral blood confirmed the 49,XXXXY karyotype in all 30 cells analyzed. The child also presented with a seizure episode at 11 months, a relatively uncommon manifestation in 49,XXXXY syndrome, which required symptomatic management. Neuroimaging revealed multiple abnormalities: A contrast-enhanced computed tomography scan of the head showed mild hydrocephalus, while magnetic resonance imaging (MRI) findings included mild restricted diffusion in the bilateral frontal and parietal subcortical white matter, white matter volume loss around the lateral ventricles, and previously unreported anomalies, such as aplasia of the frontal and sphenoid paranasal sinuses and aplasia of the left transverse and sigmoid dural venous sinuses. These findings emphasize the need to recognize 49,XXXXY syndrome as a separate clinical entity from Klinefelter syndrome due to its unique features and severe cognitive and physical impairments. This case underscores the importance of comprehensive genetic evaluation and individualized, multidisciplinary management strategies for patients with rare chromosomal abnormalities. Further research is warranted to better understand the syndrome's unique clinical presentations and develop optimal therapeutic interventions.