First Korean Case of 5q35.2q35.3 Microduplication With Reversed Sotos Syndrome Phenotype and Growth Hormone Deficiency: Expanding the Endocrine Spectrum.

Sotos syndrome is an overgrowth disorder caused by nuclear receptor binding SET domain protein 1 (NSD1) haploinsufficiency, whereas reciprocal 5q35.2q35.3 microduplication produces a reversed phenotype with growth retardation, microcephaly, delayed bone age, and neurodevelopmental delay. We describe a 43-month-old Korean girl born at 36 + 1 weeks with intrauterine growth restriction (birth weight 2200 g, length 46 cm, occipitofrontal circumference 42 cm). At presentation, all growth parameters were below the 10th percentile, with dysmorphic features including epicanthal folds, telecanthus, and a wide nasal bridge. She walked at 14 months but had an approximately 25-month language delay. Chromosomal microarray revealed a de novo 1.8 Mb duplication at 5q35.2q35.3 encompassing NSD1, classified as pathogenic (triplosensitivity score 3). A growth hormone (GH) stimulation test confirmed deficiency (peak GH 9.87 and 6.42 ng/mL). Recombinant human GH therapy (0.1 IU/kg/day) improved growth to the 5-10th percentile after 6 months. This is the first reported Korean case of 5q35.2q35.3 duplication with reversed Sotos phenotype and GH deficiency, which expands the endocrine spectrum of the disorder and underscores the need for early genetic testing and endocrine evaluation.