Von Hippel-Lindau and Hereditary Pheochromocytoma/Paraganglioma Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood

Clin Cancer Res. 2017 Jun 15;23(12):e68-e75. doi: 10.1158/1078-0432.CCR-17-0547.


Von Hippel-Lindau disease (vHL) is a hereditary tumor predisposition syndrome that places affected individuals at risk for multiple tumors, which are predominantly benign and generally occur in the central nervous system or abdomen. Although the majority of tumors occur in adults, children and adolescents with the condition develop a significant proportion of vHL manifestations and are vulnerable to delayed tumor detection and their sequelae. Although multiple tumor screening paradigms are currently being utilized for patients with vHL, surveillance should be reassessed as the available relevant clinical information continues to expand. We propose a new vHL screening paradigm similar to existing approaches, with important modifications for some tumor types, placing an emphasis on risks in childhood. This includes advancement in the timing of surveillance initiation and increased frequency of screening evaluations. Another neuroendocrine-related familial condition is the rapidly expanding hereditary paraganglioma and pheochromocytoma syndrome (HPP). The tumor spectrum for patients with HPP syndrome includes paragangliomas, pheochromocytomas, renal cancer, and gastrointestinal stromal tumors. The majority of patients with HPP syndrome harbor an underlying variant in one of the SHDx genes (SDHA, SDHB, SDHC, SDHD, SDHA, and SDHAF2), although other genes also have been described (MAX and TMEM127). Annual screening for elevated plasma or urine markers along with complete blood count and biennial whole-body MRI accompanied by focal neck MRI is recommended for older children and adults with HPP syndrome to detect tumors early and to decrease morbidity and mortality from HPP-related tumors. Clin Cancer Res; 23(12); e68-e75. ©2017 AACRSee all articles in the online-only CCR Pediatric Oncology Series.

Publication types

  • Review

MeSH terms

  • Adrenal Gland Neoplasms / diagnosis*
  • Adrenal Gland Neoplasms / epidemiology
  • Adrenal Gland Neoplasms / pathology
  • Early Detection of Cancer
  • Humans
  • Mutation
  • Neoplasm Proteins / genetics
  • Paraganglioma / diagnosis*
  • Paraganglioma / epidemiology
  • Paraganglioma / genetics
  • Paraganglioma / pathology
  • Pheochromocytoma / diagnosis*
  • Pheochromocytoma / epidemiology
  • Pheochromocytoma / genetics
  • Pheochromocytoma / pathology
  • Risk Factors
  • von Hippel-Lindau Disease / diagnosis*
  • von Hippel-Lindau Disease / epidemiology
  • von Hippel-Lindau Disease / genetics
  • von Hippel-Lindau Disease / pathology


  • Neoplasm Proteins