. A likely diagnosis of Cockayne syndrome.
. Microcephaly (pre- or post-natal onset)
. Small stature (pre- or post-natal onset)
. Persistently cold peripheries
. Bilateral hearing loss (conductive, sensorineural or mixed; not unilateral)
. Clinical cutaneous photosensitivity (n.b. skin biopsy testing of DNA repair is NOT REQUIRED)
. Joint contractures
. Progressive loss of body fat
. Brain imaging abnormality: cerebral calcification, dysmyelination or cerebellar hypoplasia (if more than one present, still count as only ONE minor criterion)
A likely diagnosis of Cockayne syndrome is defined as both major criteria and 2 minor criteria.
. Known molecular genetic diagnosis
Prior genetic testing:
. Results should have been reviewed for all genetic tests undertaken. This includes review of available exome sequencing data, but where this is the case can be limited to genes specified within disease-relevant in silico panels. The patient is not eligible if a pathogenic variant has been identified in any gene related to their phenotype.
. The following specific gene tests should be undertaken prior to recruitment to limit re-discovery of recognised pathogenic variants that could be more efficiently identified through existing diagnostic tests:
- ERCC6 (CSB) and ERCC8 (CSA).
These requirements will be kept under continual review during the main programme and may be subject to change.