Cockayne Syndrome Phenotype in a Sudanese Child With a Homozygous ERCC8 Splice-Site Variant of Uncertain Significance: A Case Report
- 1General Medicine, Independent Practice, Denver, USA
- 2Pediatrics and Child Health, Dr. Erfan & Bagedo General Hospital, Jeddah, SAU
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 premature-aging 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.
Related
- Points to consider for the reporting of variants of uncertain significance in germline genetic and genomic testing: A statement of the American College of Medical Genetics and Genomics (ACMG)
- Phenotypic Evidence for the Reclassification of the RYR1 p.(Glu4410Asp) Variant: From Uncertain Significance to Likely Benign.
- A translational pipeline for classification of variants of uncertain significance to support gene therapy clinical trial in OTOF-related deafness
- Disseminated BCG disease and recurrent pulmonary infections in a child with trisomy 21 carrying a novel BACH2 variant of uncertain significance: a 5-year case report.
- Case Report: ABCC8 variants in Chinese youth: a nine-family case series and a pragmatic three-pillar framework for adjudicating variants of uncertain significance
BibTeX
@article{ragab2026cockayne,
title = {{Cockayne Syndrome Phenotype in a Sudanese Child With a Homozygous ERCC8 Splice-Site Variant of Uncertain Significance: A Case Report}},
author = {Fatma Ragab and Alaa Alhag},
journal = {Cureus},
year = {2026},
month = sep,
doi = {10.7759/cureus.117244},
url = {https://europepmc.org/article/PMC/PMC13722474},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cockayne Syndrome Phenotype in a Sudanese Child With a Homozygous ERCC8 Splice-Site Variant of Uncertain Significance: A Case Report
AU - Fatma Ragab
AU - Alaa Alhag
PY - 2026
DA - 2026/09/30
JO - Cureus
DO - 10.7759/cureus.117244
UR - https://europepmc.org/article/PMC/PMC13722474
AB - 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 premature-aging 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.
SN - 2168-8184
ER -