Van Baars (1980) and van Baars et al. (1981, 1981, 1982) reported a large Dutch family in which 26 persons had nonchromaffin paragangliomas of the head and neck. The disorder was inherited in an autosomal pattern spanning 6 ... Van Baars (1980) and van Baars et al. (1981, 1981, 1982) reported a large Dutch family in which 26 persons had nonchromaffin paragangliomas of the head and neck. The disorder was inherited in an autosomal pattern spanning 6 generations, with increased penetrance with age. There was a fairly equal distribution of different locations in the head and neck, with the most common location at the carotid body, and a tendency toward tumor multiplicity.
In the large Dutch family with hereditary paragangliomas described by van Baars et al. (1982), Hao et al. (2009) found a missense mutation in the SDH5 gene on chromosome 11q13.1 encoding a change of a glycine at position ... In the large Dutch family with hereditary paragangliomas described by van Baars et al. (1982), Hao et al. (2009) found a missense mutation in the SDH5 gene on chromosome 11q13.1 encoding a change of a glycine at position 78 to an arginine (G78R; 613019.0001). This mutation was not detected in 400 unaffected control individuals. Within the family, the mutation was found to cosegregate with the disease haplotype in all 45 individuals who inherited this haplotype, and was not detected in 44 unaffected members without this haplotype. Thirty-three individuals with the mutation had developed the disease, but not 7 individuals (median age 74 years) who inherited the mutation from their mothers. This suggested an SDHD (602690)-like parent of origin-specific inheritance pattern. Only 5 individuals with a paternal mutation (median age 42 years) had not developed overt paragangliomas. Because penetrance of this disease increases with age, Hao et al. (2009) suggested that these individuals may develop tumors, or that tumors were already present but undetected.
Hensen et al. (2012) determined the mutation frequency of 4 succinate dehydrogenase genes in a total of 1,045 patients from 340 Dutch families with paraganglioma and pheochromocytoma. Mutations were identified in 690 cases from 239 families. The most ... Hensen et al. (2012) determined the mutation frequency of 4 succinate dehydrogenase genes in a total of 1,045 patients from 340 Dutch families with paraganglioma and pheochromocytoma. Mutations were identified in 690 cases from 239 families. The most commonly affected gene in mutation carriers was SDHD (87.1%), followed by SDHAF2 (6.7%), SDHB (185470) (5.9%), and SDHC (602413) (0.3%). Almost 70% of all carriers had the founder mutation D92Y (602690.0004) in SDHD; approximately 89% of all SDH mutation carriers had 1 of 6 Dutch founder mutations. The founder G78R mutation in SDHAF2 (613019.0001) was identified in 46 cases from 4 families. The dominance of SDHD mutations was unique to the Netherlands, contrasting with the higher prevalence of SDHB mutations found elsewhere.