Context: Inactivating mutations of SDHD, which is mapped to 11q23 and encodes the cybS subunit of succinate dehydrogenase, predispose to hereditary paraganglioma (hPGL) and/or pheochromocytoma. So far no disease was shown to occur in case of maternal transmission of a SDHD mutation, suggesting the existence of genomic imprinting. A hypothetic model, involving the loss of the maternal copy of a tumor suppressor gene mapped to 11p15 in the tumoral tissue, has been proposed to explain this mode of inheritance.

Objective: Our objective was to investigate the possibility of maternal transmission of SDHD-linked PGL.

Design: A three generations family carrying the SDHD W43X mutation was studied at the clinical, pathological and genetical levels.

Results: The germline's mutation was probably inherited from the grand-father. At the second generation three carriers (two females and one male), who had the same at risk 11q13-q23 haplotype, developed multiple cervical PGLs. At the third generation, one boy received the mutation from his mother and developed a glomus tympanicum PGL at 11. He only shared the 11q23 haplotype with the other affected members of the family. Methylation analysis of the differentially methylated region (DMR) upstream of the maternally expressed H19 gene, mapped to 11p15, showed that the seventh CTCF binding site is hypermethylated in the germline of the affected boy suggesting a gain of imprinting.

Conclusion: Our data show that maternal transmission of a SDHD-linked PGL, even if a rare event, can occur. Therefore we propose that children who inherited a pathogenic mutation from their mother should be considered as at-risk of PGL.