An aggressive and expanded phenotype in a kindred with a c.57delG SDHD mutation

Abstract

Summary Familial paraganglioma syndrome type 1 (PGL-1) is maternally imprinted, caused by SDHD mutations on the paternally inherited allele, and presents with paragangliomas and pheochromocytomas that are usually benign. We describe a kindred with a germline c.57delG SDHD mutation that demonstrates an aggressive and possibly expanded phenotype. Eight individuals across four generations were heterozygous for the c.57delG SDHD mutation. The three with known paternal inheritance were clinically affected. The aggressive phenotype was manifested by a neck paraganglioma with distant metastases, and to a lesser degree a neck paraganglioma infiltrating into local connective tissue and a pheochromocytoma presenting at age 8 y. A pulmonary capillary hemangioma may expand the SDHD phenotype. We conclude that the c.57delG SDHD mutation may confer a more aggressive and possibly expanded phenotype than other SDHD mutations. Learning points The c.57delG SDHD mutation may confer a more aggressive phenotype than other mutations associated with familial paraganglioma syndrome type 1. A capillary hemangioma, a component of other pseudohypoxia states, was observed in the lung of a single member of the c.57delG SDHD kindred. This report supports the hypothesis of others that mutations found near the beginning of the SDHD open reading frame are more likely to demonstrate an aggressive phenotype.