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

RATIONALE: 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.

PATIENT CONCERNS: A 15-year-old male presented with short stature, mild intellectual disability, epilepsy, and multiple congenital anomalies, including facial dysmorphism and right thumb syndactyly.

DIAGNOSES: 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.

INTERVENTIONS: The patient has been maintained on levetiracetam for epilepsy management and is receiving dental care for maxillofacial deformities. A multidisciplinary rehabilitation approach is recommended.

OUTCOMES: Seizures are well-controlled with no recurrence. The patient demonstrates stable cognitive and functional status under current supportive care.

LESSONS: 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.