Predictors and prevalence of paraganglioma syndrome associated with mutations of the SDHC gene

Publikation

Predictors and prevalence of paraganglioma syndrome associated with mutations of the SDHC gene

Wissenschaftlicher Artikel/Review - 26.10.2005

Schiavi Francesca, Välimäki Matti, Kawecki Andrzej, Szutkowski Zbigniew, Schipper Jörg, Walz Martin K, Pigny Pascal, Bauters Catherine, Willet-Brozick Joan E, Baysal Bora E, Januszewicz Andrzej, Eng Charis, Opocher Giuseppe, Neumann Hartmut P H, Forrer Flavio, Walter Martin A, Boedeker Carsten C, Bausch Birke, Peçzkowska Mariola, Gomez Clara Fuentes, Strassburg Thomas, Pawlu Christian, Buchta Mary, Salzmann Maren, Hoffmann Michael M, Berlis Ansgar, Brink Ingo, Cybulla Markus, Muresan Mihaela, European-American Paraganglioma Study Group

Zitation

Schiavi F, Välimäki M, Kawecki A, Szutkowski Z, Schipper J, Walz M, Pigny P, Bauters C, Willet-Brozick J, Baysal B, Januszewicz A, Eng C, Opocher G, Neumann H, Forrer F, Walter M, Boedeker C, Bausch B, Peçzkowska M, Gomez C, Strassburg T, Pawlu C, Buchta M, Salzmann M, Hoffmann M, Berlis A, Brink I, Cybulla M, Muresan M, European-American Paraganglioma Study Group. Predictors and prevalence of paraganglioma syndrome associated with mutations of the SDHC gene. JAMA 2005; 294:2057-63.

Art

Wissenschaftlicher Artikel/Review (Englisch)

Zeitschrift

JAMA 2005; 294

Veröffentlichungsdatum

26.10.2005

eISSN (Online)

1538-3598

Seiten

2057-63

Kurzbeschreibung/Zielsetzung

CONTEXT
Paraganglioma syndrome includes inherited head and neck paragangliomas (HNPs) and adrenal or extra-adrenal pheochromocytomas and are classified according to the susceptibility genes SDHB, SDHC, and SDHD. In contrast with those with germline mutations of the SDHB and SDHD genes, clinical and genetic data on patients with mutations of SDHC are scarce.

OBJECTIVE
To determine the prevalence and clinical characteristics of SDHC mutation carriers compared with patients with SDHB and SDHD mutations and with sporadic cases.

DESIGN, SETTING, AND PATIENTS
Genetic screening for SDHC mutations in an international HNP registry of 121 unrelated index cases and in 371 sporadic cases from a pheochromocytoma registry, conducted January 1, 2001, until December 31, 2004. Identified index cases and affected relatives were clinically evaluated.

MAIN OUTCOME MEASURES
Prevalence of and clinical findings for SDHC mutation-associated HNPs vs those with SDHB and SDHD mutations.

RESULTS
The prevalence of SDHC carriers was 4% in HNP but 0% in pheochromocytoma index cases. None of the SDHC mutation carriers had signs of pheochromocytoma. We compared HNPs in 22 SDHC mutation carriers with the HNPs of SDHB (n = 15) and SDHD (n = 42) mutation carriers and with 90 patients with sporadic HNPs. Location, number of tumors, malignancy, and age were different: more carotid body tumors were found in SDHC (13/22 [59%]) than in sporadic HNPs (29/90 [32%], P = .03), as well as fewer instances of multiple tumors in SDHC (2/22) than in SDHD (24/42; P<.001), 0 malignant tumors in SDHC vs 6/15 in SDHB (P = .002), and younger age at diagnosis in SDHC than in sporadic HNPs (45 vs 52 years; P = .03).

CONCLUSIONS
Patients with HNP, but not those with pheochromocytoma, harbor SDHC mutations in addition to those in SDHB and SDHD. In total, more than one quarter of HNP patients carry a mutation in 1 of these 3 genes. Head and neck paragangliomas associated with SDHC mutations are virtually exclusively benign and seldom multifocal. Analysis for germline mutations of SDHC is recommended in apparently sporadic HNP to identify risk of inheritance.