The majority of Dutch patients with HNPGL present with a positive family history, in contrast to other European countries. The clinical characteristics of patients with HNPGL are chiefly determined by founder mutations in SDHD, the major causative gene in both familial and isolated patients with HNPGL. The high frequency of founder mutations in SDHD suggests a higher absolute prevalence of paraganglioma syndrome in the Netherlands.

The authors report clinical and radiologic characteristics and ultimate diagnosis in 12 patients with a regressing cerebral mass lesion. Primary CNS lymphoma (PCNL) was found in only half of the patients with such a lesion. In patients showing a complete resolution of the enhancing lesion the probability of finding a PCNL is smaller and survival is longer.

Germline mutations in SDHD predispose to the development of head and neck paragangliomas, and phaeochromocytomas. The risk of developing a tumor depends on the sex of the parent who transmits the mutation: paragangliomas only arise upon paternal transmission. In this study, both the risk of paraganglioma and phaeochromocytoma formation, and the risk of developing associated symptoms were investigated in 243 family members with the SDHD.D92Y founder mutation. By using the Kaplan-Meier method, age-specific penetrance was calculated separately for paraganglioma formation as defined by magnetic resonance imaging (MRI) and for paraganglioma-related signs and symptoms. Evaluating clinical signs and symptoms alone, the penetrance reached a maximum of 57% by the age of 47 years. When MRI detection of occult paragangliomas was included, penetrance was estimated to be 54% by the age of 40 years, 68% by the age of 60 years and 87% by the age of 70 years. Multiple tumors were found in 65% and phaeochromocytomas were diagnosed in 8% of paraganglioma patients. Malignant paraganglioma was diagnosed in one patient (3%). Although the majority of carriers of a paternally inherited SDHD mutation will eventually develop head and neck paragangliomas, we find a lower penetrance than previous estimates from studies based on predominantly index cases. The family-based study described here emphasizes the importance of the identification and inclusion of clinically unaffected mutation carriers in all estimates of penetrance. This finding will allow a more accurate genetic counseling and warrants a 'wait and scan' policy for asymptomatic paragangliomas, combined with biochemical screening for catecholamine excess in SDHD-linked patients.

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The objective of this study was to assess the long-term survival of patients with a paraganglioma of the head and neck compared with the survival of the general Dutch population. This historic cohort study was conducted using nationwide historical data of paraganglioma patients. We retrieved a cohort of 86 patients diagnosed with a paraganglioma of the head and neck between 1945 and 1960 in the Netherlands. Dates of death were retrieved from the national bureau of genealogy. Survival after diagnosis was compared with age and sex adjusted survival in the general population, by means of Wilcoxon signed rank test and Kaplan-Meier actuarial survival curves. Although surgery had more complications in the studied era than today and the death of five patients with carotid body tumors caused immediate excess mortality, the survival of the followed cohort was not significantly reduced if compared with the general population. Paragangliomas of the head and neck do not reduce life expectancy.