Genetics of Cockayne Syndrome Workup

A thorough evaluation is recommended for anyone who is suspected of having Cockayne syndrome to confirm the diagnosis, exclude other possible diagnoses, and establish the extent of the disease. The evaluation includes the following:

• Genetic evaluation
• Developmental evaluation
• Ophthalmologic evaluation
• Neurologic evaluation
• Gastrointestinal evaluation with a nutritionist
• Audiologic evaluation
• Dermatologic evaluation
• Dental evaluation

Unless the clinical suspicion is confirmed, it is difficult to offer the appropriate genetic counseling, discuss associated morbidities and mortality, and refer the patient to available subspecialists and Cockayne syndrome support groups.  

In patients with suspected Cockayne syndrome (CS), perform routine laboratory tests to exclude other disorders and to establish baseline renal function.

For growth failure, request chromosome analysis and chromosome microarray testing to exclude any karyotypic abnormalities. An endocrine evaluation may be helpful to determine any hormonal causes of growth failure, and baseline metabolic studies are useful.

Request chromosome breakage studies if considering Bloom syndrome in the differential diagnosis. Patients with xeroderma pigmentosum (a differential diagnosis for Cockayne syndrome type 1 and Bloom syndrome demonstrate clinical phenotypes that overlap with those found in patients with Cockayne syndrome. Chromosome breakage studies and DNA mutation analysis are necessary to exclude Bloom syndrome and xeroderma pigmentosum.

Cultured skin fibroblasts of patients with Cockayne syndrome type I lack the ability to form colonies when subjected to UV irradiation. Very few laboratory personnel have expertise in this technique, and, given the availability of genetic testing, skin biopsy and analysis have become less important and/or useful.

Mutational analysis of the genes ERCC8 and ERCC6, associated with Cockayne syndrome, are available at a few clinical laboratories across the country.

Computed tomography (CT) or magnetic resonance imaging (MRI) scan findings include increased ventricular size, cerebral atrophy, white matter abnormalities, and normal pressure hydrocephaly.

Skeletal radiographs depict vertebral body and pelvic abnormalities.

Additional tests include the following:

• Audiometry - Used to determine if sensorineural hearing loss has occurred
• Electroencephalography - Used to assess the patient for seizure activity
• Nerve conduction studies - Used to evaluate for the presence of a demyelinating neuropathy
• Electroretinography - Reveals abnormalities in the electric potential of the retina

Ocular histopathologic findings indicate degeneration of all retinal layers. Pigment migrates into the photoreceptor layer. Nerve fiber bundles of the optic nerve head become markedly thin, while partial demyelination of the remaining nerves occurs.

For patients with sensorineural hearing loss, a significant loss of neurons occurs in the spiral ganglion and brainstem, with retrograde atrophy of the auditory pathways.