Evaluation of SDHB, SDHD and VHL gene susceptibility testing in the assessment of individuals with non-syndromic phaeochromocytoma, paraganglioma and head and neck paraganglioma

Clin Endocrinol (Oxf). 2013 Jun;78(6):898-906. doi: 10.1111/cen.12074. Epub 2013 Apr 6.


Objectives: Research studies have reported that about a third of individuals with phaeochromocytoma/paraganglioma (PPGL) have an inherited predisposition, although the frequency of specific mutations can vary between populations. We evaluated VHL, SDHB and SDHD mutation testing in cohorts of patients with non-syndromic PPGL and head and neck paraganglioma (HNPGL).

Design: Prospective, observational evaluation of NHS practice.

Patients: Individuals with PPGL/HNPGL referred to a supraregional genetics testing service over a 10-year period.

Measurements: Clinical (age, tumour site, malignancy, etc.), mutation frequencies and characteristics.

Results: A total of 501 probands with PPGL (n = 413) or HNPGL (n = 88) were studied. Thirty-one percent of patients with PPGL presented had a pathogenic mutation in SDHB, SDHD or VHL. Mutation detection rates were highest in those with a positive family history (62%), malignancy (53%), multiple tumours (33%) or PGL (44%). Twenty-eight percent of individuals with a single sporadic phaeochromocytoma had a mutation. Overall, 63% of patients with HNPGL had a mutation (92% of those with a family history, 89% of those with multicentric tumours and 34% of those with a single sporadic HNPGL). Penetrance was calculated in 121 SDHB mutation-positive probands and 187 of their mutation-positive relatives. Most relatives were asymptomatic and lifetime penetrance in non-proband SDHB mutation carriers was <50%.

Conclusions: Practice-based evaluations of genetic testing in PPGL reveal high mutation detection rates. Although clinical criteria can be used to prioritize mutation testing, mutations were detected in 'low risk groups' indicating a need for comprehensive and inexpensive genetic testing strategies for PPGL and HNPGL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Gland Neoplasms / genetics*
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Head and Neck Neoplasms / genetics*
  • Humans
  • Middle Aged
  • Paraganglioma / genetics*
  • Pheochromocytoma / genetics*
  • Prospective Studies
  • Succinate Dehydrogenase / genetics*
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics*


  • SDHD protein, human
  • SDHB protein, human
  • Succinate Dehydrogenase
  • Von Hippel-Lindau Tumor Suppressor Protein
  • VHL protein, human