27th May 2025

Aetiology

Whilst the majority occur sporadically, hereditary syndromes such as the following account for a 40% of cases in adults and 80% of cases in children:

• Multiple endocrine neoplasia type 2A and 2B due to the RET gene – occurring bilaterally in 70% of MEN syndromes.
• Von Hippel-Lindau disease due to the VHL gene – also associated with cerebellar haemangioblastomas and renal cell carcinomas.
• Neurofibromatosis type 1 due to the NF1 gene – with an incidence of 1% of phaechromocytoma.
• Paraganglioma syndromes types 1, 3 and 4.

Germline or somatic mutations can affect over 20 different genes, affecting metabolism e.g. succinate dehydrogenase or signalling pathways e.g. kinase and Wnt.