Context Germline mutations of the genes encoding succinate dehydrogenase subunits
B (SDHB) and D (SDHD) predispose
to paraganglioma syndromes type 4 (PGL-4) and type 1 (PGL-1), respectively.
In both syndromes, pheochromocytomas as well as head and neck paragangliomas
occur; however, details for individual risks and other clinical characteristics
Objective To determine the differences in clinical features in carriers of SDHB mutations and SDHD mutations.
Design, Setting, and Patients Population-based genetic screening for SDHB and SDHD germline mutations in 417 unrelated patients with
adrenal or extra-adrenal abdominal or thoracic pheochromocytomas (n = 334)
or head and neck paragangliomas (n = 83), but without syndromic features,
from 2 registries based in Germany and central Poland, conducted from April
1, 2000, until May 15, 2004.
Main Outcome Measures Demographic and clinical findings with respect to gene mutation in SDHB vs SDHD compared with nonmutation
Results A total of 49 (12%) of 417 registrants carried SDHB or SDHD mutations. In addition, 28 SDHB and 23 SDHD mutation carriers
were newly detected among relatives of these carriers. Comparison of 53 SDHB and 47 SDHD total mutation
carriers showed similar ages at diagnosis but differences in penetrance and
of tumor manifestations. Head and neck paragangliomas (10/32 vs 27/34, respectively, P<.001) and multifocal (9/32 vs 25/34, respectively, P<.001) tumors were more frequent in carriers of SDHD mutations. In contrast, SDHB mutation
carriers have an increased frequency of malignant disease (11/32 vs 0/34, P<.001). Renal cell cancer was observed in 2 SDHB mutation carriers and papillary thyroid cancer in 1 SDHB mutation carrier and 1 SDHD mutation
Conclusions In contrast with SDHD mutation carriers (PGL-1)
who have more frequent multifocal paragangliomas, SDHB mutation
carriers (PGL-4) are more likely to develop malignant disease and possibly
extraparaganglial neoplasias, including renal cell and thyroid carcinomas.
Appropriate and timely clinical screening is recommended in all patients with
PGL-1 and PGL-4.