Genetics of hereditary head and neck paragangliomas

Head Neck. 2014 Jun;36(6):907-16. doi: 10.1002/hed.23436. Epub 2013 Nov 30.

Abstract

Background: The purpose of this study was to give an overview on hereditary syndromes associated with head and neck paragangliomas (HNPGs).

Methods: Our methods were the review and discussion of the pertinent literature.

Results: About one third of all patients with HNPGs are carriers of germline mutations. Hereditary HNPGs have been described in association with mutations of 10 different genes. Mutations of the genes succinate dehydrogenase subunit D (SDHD), succinate dehydrogenase complex assembly factor 2 gene (SDHAF2), succinate dehydrogenase subunit C (SDHC), and succinate dehydrogenase subunit B (SDHB) are the cause of paraganglioma syndromes (PGLs) 1, 2, 3, and 4. Succinate dehydrogenase subunit A (SDHA), von Hippel-Lindau (VHL), and transmembrane protein 127 (TMEM127) gene mutations also harbor the risk for HNPG development. HNPGs in patients with rearranged during transfection (RET), neurofibromatosis type 1 (NF1), and MYC-associated factor X (MAX) gene mutations have been described very infrequently.

Conclusion: All patients with HNPGs should be offered a molecular genetic screening. This screening may usually be restricted to mutations of the genes SDHD, SDHB, and SDHC. Certain clinical parameters can help to set up the order in which those genes should be tested.

Keywords: head and neck paraganglioma; hereditary cancer; paraganglioma syndrome; pheochromocytoma; rare diseases.

Publication types

  • Review

MeSH terms

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Carcinoma, Renal Cell / genetics
  • Diagnosis, Differential
  • Gastrointestinal Stromal Tumors / genetics
  • Genetic Testing
  • Germ-Line Mutation*
  • Head and Neck Neoplasms / genetics*
  • Heterozygote
  • Humans
  • Kidney Neoplasms / genetics
  • Membrane Proteins / genetics
  • Mitochondrial Proteins / genetics
  • Multiple Endocrine Neoplasia Type 1 / genetics
  • Neoplastic Syndromes, Hereditary / genetics
  • Neurofibromatosis 1 / genetics
  • Paraganglioma / genetics*
  • Succinate Dehydrogenase / genetics*
  • von Hippel-Lindau Disease / genetics

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • MAX protein, human
  • Membrane Proteins
  • Mitochondrial Proteins
  • SDHAF2 protein, human
  • SDHC protein, human
  • SDHD protein, human
  • TMEM127 protein, human
  • SDHB protein, human
  • Succinate Dehydrogenase

Supplementary concepts

  • Paragangliomas 2
  • Paragangliomas 3