Background information
Hereditary paraganglioma-phaeochromocytoma syndromes are characterised by paragangliomas and phaeochromocytomas which are tumours derived from neuroendocrine tissues distributed along the paravertebral axis from the base of the skull to the pelvis.
Phaeochromocytomas and paragangliomas are rare and usually sporadic. Hereditary cases are characterised by earlier age of onset, malignancy, multiple tumours and family history.
Approximately 30% of all PGL PCC cases are thought to be due to germline pathogenic mutations, with 24-28% of apparently sporadic PCC having a familial basis.
Testing strategy
Clinically affected probands:
For NHS England funded patients, where R223 analysis is required alongside other cancer panels, then this analysis will all be undertaken in Oxford on a single technical platform
NHSE funded referrals for isolated analysis of R223 will be exported within the GLH, to the West Midlands Regional Genetics Laboratory, in accordance with the funding models
R223.1 - analysis for small variants in the gene panel indicated below
Genes tested:
Genes analysed are in accordance with the 'green' high evidence of clinical association gene list in panel app.
Targeted analysis for known / previously reported familial variants:
Presymptomatic testing in clinically unaffected family members at risk of inheriting a previously reported familial pathogenic variant (R242)
Diagnostic confirmation in individuals at risk of inheriting a previously reported familial pathogenic variant and clinically suspected of having the familial condition (R240)
Segregation studies in affected family members to aid variant interpretation (R375)
Prenatal diagnosis is not typically requested
Sample requirements and referral information
Requesting specialties:
Endocrinology
Clinical Genetics
