Cockayne Syndrome Phenotype in a Sudanese Child With a Homozygous ERCC8 Splice-Site Variant of Uncertain Significance: A Case Report
Year: 2026
Type: article
Study design: Case Report
Abstract: Cockayne syndrome (CS) is a rare autosomal recessive DNA repair disorder caused by biallelic pathogenic variants in excision repair cross-complementation group 6 (ERCC6) or group 8 (ERCC8) and characterized by progressive postnatal growth failure, neurodevelopmental impairment, photosensitivity, and prematureaging features.Its evolving multisystem phenotype can complicate early clinical recognition, particularly when molecular testing identifies a variant of uncertain significance (VUS).We report a Sudanese girl residing in Saudi Arabia, born to consanguineous parents, with normal birth parameters and initially satisfactory development who, from late infancy, developed progressive postnatal growth failure, acquired microcephaly, and global developmental delay.Subsequent photosensitivity, progeroid features, spasticity, ataxia, tremor, and reported hearing and visual impairment raised clinical suspicion for CS, although Sanjad-Sakati syndrome was initially considered.Whole-exome sequencing (WES) identified a homozygous canonical acceptor splice-site variant in ERCC8 (NM_000082.3:c.482-2A>T),predicted to disrupt normal splicing.Although listed as likely pathogenic in ClinVar, it was classified by the testing laboratory as a VUS.Given the strong phenotypic concordance, the variant was interpreted as supportive of, but not independently diagnostic for, CS.This case underscores the importance of longitudinal phenotypic assessment for recognizing CS and highlights the need for cautious integration of molecular findings with the clinical phenotype when genetic testing identifies a VUS.
Source: Cureus
Authors: Fatma Ragab, Alaa Alhag
Language: English
Topic: Genomics and Rare Diseases
Subfield: Genetics
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7214936308