Lamb-Shaffer syndrome in a Chinese adolescent: A case report.

Lamb-Shaffer syndrome (LAMSHF) is a rare neurodevelopmental disorder caused by pathogenic variants in the SRY-related high-mobility group box 5 (SOX5) gene. Clinical features are heterogeneous, and novel variants continue to be reported, expanding the genotypic and phenotypic spectrum of the disease. A 15-year-old male presented with short stature, mild intellectual disability, epilepsy, and multiple congenital anomalies, including facial dysmorphism and right thumb syndactyly. Whole-exome sequencing identified a novel heterozygous variant in the SOX5 gene, c.1160G>A (p.Ser387Asn), located at 12p12.1. Although initially classified as a variant of uncertain significance according to ACMG criteria, its strong correlation with the clinical phenotype supported the diagnosis of LAMSHF. The patient has been maintained on levetiracetam for epilepsy management and is receiving dental care for maxillofacial deformities. A multidisciplinary rehabilitation approach is recommended. Seizures are well-controlled with no recurrence. The patient demonstrates stable cognitive and functional status under current supportive care. This case reports a novel SOX5 variant associated with LAMSHF and highlights the importance of genetic confirmation in patients with unexplained neurodevelopmental features to guide appropriate management and avoid unnecessary interventions.