Hereditary paraganglioma (PGL)

Familial nonchromaffin paragangliomas , Familial glomus tumors , Chemodectomas , Carotid body tumors , Glomus jugulare tumors

Follows an autosomal dominant pattern. This pattern is associated with a maternal genomic imprinting for SDHD gene
 , 35% of head and neck paragangliomas are inherited.

115310 , 168000 , 601650 , 605373

D010235

29072 Hereditary pheochromocytoma-paraganglioma

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Paragangliomas are highly vascularized tumors derived from neuroectodermal cells. In the familial forms, they are preferentially localized in the head and neck, in the carotid body (80%) and in the glomus jugulare (20%). They may be associated with other neural-crest-derived tumors such as pheochromocytomas. Individuals with familial paragangliomas have a more severe presentation (early age at onset and tumors at multiple sites) than do those with sporadic disease.

Tumors are usually benign. Their gravity result of local invasion and important vascularisation. Among 10% of paraganglioma have a malignant evolution.

Early detection and surgery

depends on extent of the disease at the time of diagnosis

SDH4

4 exons

wide

SDHD encodes a mitochondrial respiratory-chain protein of complex II called \"cybS\"or small subunit of cytochrome b in succinate-ubiquinone oxidoreductase.

Germ-line mutations in PGL patients are heterozygous and lead to protein truncation (false-sense mutations, insertions and deletions). Missense mutations are also described.

Loss of wild type allele was usually observed in accordance with the two-hit model for neoplasia.

SDH3

7 exons

wide

SDHC encodes a mitochondrial respiratory-chain protein of complex II called \"cybL\"or large subunit of cytochrome b in succinate-ubiquinone oxidoreductase. This protein participates with cybS to the anchorage of the complex II in the innner mitochondrial membrane.

Destruction of start codon ATG by a G-to-A transition in exon 1 of SDHC.

Loss of wild type allele in tumor DNA.

SDH1

8 exons

wide

SDHB encodes a mitochondrial respiratory-chain protein of complex II called iron-sulfur protein. This protein participates with the flavoprotein, encoded by SDHA gene, to the enzymatic reaction which proceed to the oxydation of succinate in fumarate coupled with the reduction of ubiquinone to ubiquinol.

Missense mutation leading to protein truncation.

Not determined.