Compound heterozygous mutations in CC2D2A cause Meckel-Gruber syndrome: a case report and review of the literature.

BACKGROUND: Meckel-Gruber syndrome is a rare autosomal recessive ciliopathy characterized by the triad of occipital encephalocele, polycystic kidney dysplasia, and postaxial polydactyly, with an estimated incidence of 1:13,250 to 1:140,000 live births. Pathogenic variants in CC2D2A, encoding a ciliary transition zone protein, account for 5-15% of MGS cases. This report highlights the diagnostic utility of whole-exome sequencing (WES) in delineating molecular etiologies of MGS and reviews genotype-phenotype correlations associated with CC2D2A mutations.

CASE PRESENTATION: A 30-year-old Chinese primigravida (G1P0) from Shandong Province was referred at 23 week gestation following prenatal ultrasound detection of fetal anomalies. Key findings included bilateral enlarged hyperechoic kidneys (renal transverse diameter: 35 mm, > 95th percentile), occipital meningoencephalocele (29 × 25 × 12 mm) and bilateral postaxial hexadactyly. Prenatal counseling confirmed the fetal prognosis, and the parents chose to terminate the pregnancy. Postmortem WES revealed compound heterozygous CC2D2A variants.

CONCLUSIONS: This case highlights that prenatal ultrasonography remains critical for early detection of MGS hallmarks, especially in resource-limited Settings. Second, WES-based molecular autopsy is crucial for definitive diagnosis and genetic counseling.