General description

Cockayne syndrome (CS) is caused by mutations in two primary genes: ERCC6 (CSB) and ERCC8 (CSA), with approximately 65-70% of cases attributed to CSB mutations and 30-35% to CSA mutations. These genes encode proteins essential for transcription-coupled nucleotide excision repair (TC-NER), a specialized DNA repair pathway that removes lesions from actively transcribed genes.

Cockayne syndrome is characterized by severe growth failure, leading to short stature and low body weight from an early age. This condition results in a prematurely aged appearance due to the loss of subcutaneous fat.

Neurological symptoms are central to the disease, including progressive microcephaly, intellectual disability, unsteady gait, tremors, spasticity, abnormal reflexes, peripheral neuropathy, and, in some cases, seizures.

Sensory impairments include progressive vision loss due to pigmentary retinopathy and cataracts, as well as hearing loss and optic atrophy.

Patients often exhibit extreme sensitivity to UV light, leading to skin damage and premature aging. Characteristic craniofacial features include sunken eyes, prominent ears, a thin nose, and a distinctive "bird-like" facial appearance. Dental anomalies such as enamel hypoplasia and caries are also common.

Other manifestations include joint contractures, hepatosplenomegaly in some cases, and an increased risk of hypertension, renal disease, and diabetes.

References

1. Karikkineth, Ajoy C., et al. "Cockayne syndrome: Clinical features, model systems and pathways." Ageing research reviews 33 (2017): 3-17.
2. Koob, M., et al. "Neuroimaging in Cockayne syndrome." American journal of neuroradiology 31.9 (2010): 1623-1630.