Familial Occurrence of Cockayne Syndrome: Clinical Insights from Northern India

Abstract

Background: Cockayne Syndrome (CS) is a rare autosomal recessive neurodegenerative disorder caused by pathogenic variants in ERCC6 (CSB) or ERCC8 (CSA). Key clinical clues include cachexia, microcephaly, characteristic “bird-like” facies, neurodevelopmental regression, sensorineural deficits, and dental anomalies. Radiologically, CS features a characteristic pattern of diffuse hypomyelination, cerebral and cerebellar atrophy, and progressive white matter changes, making MRI a critical adjunct to diagnosis. Case Report and Discussion: We present two affected siblings from a non-consanguineous family with clinical features of CS, including postnatal growth failure, cachectic habitus, bird-like facies, neurodevelopmental regression, and white matter changes with cerebellar atrophy on MRI. Molecular testing identified a homozygous pathogenic ERCC6 variant (c.4063+1G>C) in the affected sibling, confirming the diagnosis. A three-generation pedigree supporting autosomal recessive inheritance is included. Conclusion: This report highlights the phenotype–genotype correlation ansd the importance of neuroimaging and genetic testing for diagnosis, family counseling, and reproductive planning in CS. Early diagnosis enables appropriate supportive care and informed reproductive counseling. Reporting genetically confirmed cases from diverse populations remains important to expand understanding of the disease spectrum and to guide future therapeutic efforts.