Clinical features of paraganglioma syndromes.

Head and neck paragangliomas (HNPs) and pheochromocytomas are rare tumors. Sporadic and hereditary forms are recognized. Four different paraganglioma syndromes (PGLs 1-4) have been described: PGL 1 is associated with mutations of the succinate dehydrogenase (SDH) subunit D (SDHD) gene; PGL 3 is caused by SDHC gene mutations; PGL 4 is caused by SDHB gene mutations; the susceptibility gene for PGL 2 is unknown. The objective of this study is to review distinct clinical features of the different PGLs. An international registry for HNPs was founded in Freiburg, Germany, in 2000. The data presented in this article have been acquired from registered HNP patients who have been screened for mutations of the genes SDHB, SDHC, and SDHD. Approximately 30% of apparent sporadic HNPs are caused by a germline mutation in one of these genes. Patients with PGL 1 or 4 have a very high lifetime risk of developing HNPs as well as thoracic and abdominal pheochromocytomas. Compared with sporadic HNPs, tumors developing in SDHB, SDHC, and SDHD mutation carriers arise at a significantly younger age. The SDHB mutations are associated with a high percentage of malignant paraganglionic tumors. We recommend molecular genetic screening of all HNP patients for SDHB, SDHC, and SDHD gene mutations. Mutation carriers must be screened for paraganglial tumors in the head, neck, thorax, and abdomen. Appropriately timed surgical intervention will minimize disease-specific morbidity and mortality. Lifelong follow-up is mandatory.

[1]  K. Lackner,et al.  Malignant paraganglioma caused by a novel germline mutation of the succinate dehydrogenase D‐gene—A case report , 2008, Head & neck.

[2]  J. Bertherat,et al.  Mutations associated with succinate dehydrogenase d‐related malignant paragangliomas , 2008, Clinical endocrinology.

[3]  C. Eng,et al.  Extra-adrenal and adrenal pheochromocytomas associated with a germline SDHC mutation , 2008, Nature Clinical Practice Endocrinology &Metabolism.

[4]  C. Eng,et al.  Predictors and prevalence of paraganglioma syndrome associated with mutations of the SDHC gene. , 2005, JAMA.

[5]  R. Ferrell,et al.  An Alu-mediated partial SDHC deletion causes familial and sporadic paraganglioma , 2004, Journal of Medical Genetics.

[6]  E. Jordanova,et al.  Somatic loss of maternal chromosome 11 causes parent-of-origin-dependent inheritance in SDHD-linked paraganglioma and phaeochromocytoma families , 2004, Oncogene.

[7]  Jeffrey E. Lee,et al.  Surgical management of hereditary pheochromocytoma. , 2004, Journal of the American College of Surgeons.

[8]  B. Baysal.  On the association of succinate dehydrogenase mutations with hereditary paraganglioma , 2003, Trends in Endocrinology & Metabolism.

[9]  Jeffrey E. Lee,et al.  The role of genetics in the surgical management of familial endocrinopathy syndromes. , 2003, Journal of the American College of Surgeons.

[10]  P. Rustin,et al.  Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas. , 2003, Cancer research.

[11]  H. Neumann,et al.  Paragangliomas in patients with mutations of the SDHD gene , 2003, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[12]  E. Leteurtre,et al.  Hereditary phaeochromocytomas and paragangliomas: a study of five susceptibility genes , 2003, Journal of medical genetics.

[13]  U. Müller,et al.  Autosomal dominant malignant and catecholamine-producing paraganglioma caused by a splice donor site mutation in SDHC , 2003, Human Genetics.

[14]  J. Schipper,et al.  18F-DOPA positron emission tomography for the detection of glomus tumours , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[15]  J. Strauchen.  Germ-line mutations in nonsyndromic pheochromocytoma. , 2002, The New England journal of medicine.

[16]  B. Baysal.  Hereditary paraganglioma targets diverse paraganglia , 2002, Journal of medical genetics.

[17]  D. Frank,et al.  Combined endovascular and surgical treatment of head and neck paragangliomas—A team approach , 2002, Head & neck.

[18]  W. Rubinstein,et al.  Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas , 2002, Journal of medical genetics.

[19]  L. Karnell,et al.  National Cancer Data Base report on malignant paragangliomas of the head and neck , 2002, Cancer.

[20]  E S Husebye,et al.  Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. , 2001, American journal of human genetics.

[21]  D. Evans,et al.  Germline SDHD mutation in familial phaeochromocytoma , 2001, The Lancet.

[22]  C. Eng,et al.  Somatic and occult germ-line mutations in SDHD, a mitochondrial complex II gene, in nonfamilial pheochromocytoma. , 2000, Cancer research.

[23]  Ulrich Müller,et al.  Mutations in SDHC cause autosomal dominant paraganglioma, type 3 , 2000, Nature Genetics.

[24]  D. Turnbull,et al.  Late‐onset optic atrophy, ataxia, and myopathy associated with a mutation of a complex II gene , 2000, Annals of neurology.

[25]  B. Devlin,et al.  Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. , 2000, Science.

[26]  C Eng,et al.  The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. , 1996, JAMA.

[27]  H. Neumann,et al.  Pheochromocytomas, multiple endocrine neoplasia type 2, and von Hippel-Lindau disease. , 1993, The New England journal of medicine.

[28]  John C. Dailey,et al.  Familial Multiple Cervical Paragangliomas: Report of a Kindred and Review of the Literature , 1990, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[29]  V. M. Riccardi,et al.  Von Recklinghausen neurofibromatosis. , 1981, The New England journal of medicine.

[30]  G. Alderman.  National , 1896, The Journal of comparative medicine and veterinary archives.

[31]  J. Schipper,et al.  Malignant Paragangliomas in SDHB Mutation Carriers , 2006 .

[32]  J. Schipper,et al.  Paragangliomas of the head and neck: diagnosis and treatment , 2004, Familial Cancer.

[33]  T. Bley,et al.  Imaging of pheochromocytoma and paraganglioma , 2004, Familial Cancer.

[34]  L. Aaltonen,et al.  Early-onset renal cell carcinoma as a novel extraparaganglial component of SDHB-associated heritable paraganglioma. , 2004, American journal of human genetics.

[35]  W. Chase.  Familial and bilateral tumours of the carotid body , 1933 .