Clinical Guidance

To date no clear genotype-phenotype correlations for ERCC6 or ERCC8 have been identified. In one study, individuals with pathogenic variants in ERCC8 appeared to have significantly less severe manifestations than ERCC6 at the time of the diagnosis . For individuals with pathogenic variants in ERCC6, variants upstream of a transposon called PiggyBac transposable element-derived protein 3 in intron 5 of ERCC6 were found to be associated with less severe features than pathogenic variants downstream of that transposon insertion .

Source: GeneReviews — "Cockayne Syndrome"

Diagnostic Criteria

Formal clinical diagnostic criteria originally proposed for Cockayne syndrome (CS) type I were revised and subsequently expanded . A diagnostic scoring system has been recently proposed based on both clinical and imaging criteria . Cockayne syndrome is characterized by growth failure and multisystemic involvement, with a variable age of onset and rate of progression. Due to the progressive nature of CS, the clinical diagnosis becomes more certain as additional clinical manifestations gradually evolve over time. To facilitate clinical recognition and follow up, the phenotypic spectrum of CS can be divided into different clinical presentations. Note, however, that among all individuals with CS there is a continuous spectrum of clinical severities and that intermediate phenotypes may arise.

Source: GeneReviews — "Cockayne Syndrome"

Differential Diagnosis

The differential diagnosis of Cockayne syndrome (CS) depends on the presenting features of the individual. Abnormalities that suggest alternative diagnoses include congenital anomalies of the face, limbs, heart, or viscera; recurrent infections (other than otitis media or respiratory infections); metabolic or neurologic crises; hematologic abnormality (e.g., anemia, leukopenia); and cancer of any kind.

Table 4.

Disorders to Consider in the Differential Diagnosis of Cockayne Syndrome

Gene(s) | Disorder | MOI | Key Feature(s) Overlapping w/CS | Distinguishing Features

PLP1 | Severe "connatal" Pelizaeus-Merzbacher disease (See PLP1 Disorders.)1 | XL | White matter abnormalities growth restriction | Severe growth failure distinctive physical appearance in CS

Source: GeneReviews — "Cockayne Syndrome"

Management Guidelines

No clinical practice guidelines for Cockayne syndrome (CS) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with CS, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 5. Cockayne Syndrome: Recommended Evaluations Following Initial Diagnosis

Source: GeneReviews — "Cockayne Syndrome"

Clinical Guidance

Excessive sun exposure should be avoided. Use of metronidazole should be avoided in any circumstance (risk of severe hepatitis) . Extra vigilance is needed for opioid and sedative use due to exaggerated response to these types of medications . Growth hormone (GH) levels in individuals with CS may be elevated or decreased . While individuals with CS do not appear to be at increased risk for malignancy (an effect which may be due to simultaneous transcription and cell proliferation deficiency), it is theoretically possible that GH treatment could reverse this compensatory effect and promote tumor growth. Therefore, in the absence of safety and efficacy data, GH treatment cannot be recommended in individuals with CS.

Source: GeneReviews — "Cockayne Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. There is currently no therapy that has been proved useful in this disorder.

Source: GeneReviews — "Cockayne Syndrome"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Yearly assessment for known potential complications (e.g., hypertension, renal or hepatic dysfunction, declining vision and hearing) is appropriate . Table 7. Cockayne Syndrome: Recommended Surveillance

Source: GeneReviews — "Cockayne Syndrome"