Cockayne syndrome: The expanding clinical and mutational spectrum

Cockayne syndrome is a progressive multisystem disorder characterized by a specific cellular defect in transcription-coupled repair. Typical features include developmental delay, failure to thrive, microcephaly, cutaneous photosensitivity, dental anomalies, progressive hearing loss, pigmentary retinopathy, cataracts and enophthalmia. Various levels of severity have been described including the “classical” or moderate type I CS, the early-onset or severe type II and the mild or late-onset type III. Adult-onset cases with prolonged survival and normal initial development have also been identified. At the opposite end of the scale, the most severely affected patients, showing a prenatal onset of the symptoms, are overlapping with the cerebro-oculo-facio-skeletal (COFS) syndrome. These overlapping subtypes build a continuous spectrum without clear thresholds. Revised diagnostic criteria are proposed to improve the recognition of the disease. Two thirds of the patients are linked to mutations in the CSB (ERCC6) gene, one third to mutations in the CSA (ERCC8) gene. At least 78 different mutations are known in the CSB gene and 30 in the CSA gene to date, in more than 120 genetically confirmed patients. Large clinical and molecular databases are needed to unravel genotype-phenotype correlations and to gain more insight into the underlying molecular mechanisms.

► The overlapping subtypes of Cockayne syndrome build a continuous spectrum.
► Revised diagnostic criteria are proposed to improve the recognition of the disease.
► Two thirds of the patients are linked to mutations in the CSB (ERCC6) gene.
► One third of the patients is linked to mutations in the CSA (ERCC8) gene.
► Clinical and molecular databases are needed for genotype–phenotype correlations.