Cerebro-oculo-facio-skeletal (COFS) syndrome is a rare autosomal recessive inherited disorder characterized by microcephaly, congenital cataracts and/or microphthalmia, arthrogryposis, developmental delay, and facial dysmorphism. It is now recognized as a disorder belonging to the spectrum of inherited defects in nucleotide excision repair. Hereby, we report a 13-month-old female, the second born of third-degree consanguineous marriage, who presented with neuroregression. She had microcephaly, nystagmus, bilateral congenital cataracts, hypotonia, and absent deep tendon reflexes. Neuroimaging showed diffuse hypomyelination of the bilateral cerebral white matter, suggesting hypomyelinating leukodystrophy. Whole exome sequencing revealed a homozygous pathogenic variant in exon 19 of the excision repair cross-complementation 2 gene, confirming COFS syndrome. So far, 14 cases described as COFS syndrome have been studied at the molecular level. This case highlights the importance of early recognition of neuro-regression alongside a systematic approach with early genetic evaluation to narrow down to the correct diagnosis. Given its rarity, this case report contributes significantly to the understanding of its clinical spectrum and potential management strategies.
Basha et al. (Fri,) studied this question.