SDHB-Associated Paraganglioma Syndrome in Africa—A Need for Greater Genetic Testing

Abstract

A germline mutation is identified in almost 40% of Pheochromocytoma-Paraganglioma (PPGL) Syndromes. Genetic testing and counselling are essential for the management of index cases as well as pre-symptomatic identification and pre-emptive management of affected family members. Mutations in the genes encoding the mitochondrial enzyme succinate dehydrogenase (SDH) are well described in patients with hereditary PPGL. Amongst patients of African ancestry the prevalence, phenotype, germline mutation spectrum and penetrance of SDH mutations is poorly characterized. We describe a multifocal paraganglioma in a young African male with an underlying mis-sense SDHB mutation, with a history of three first-degree relatives who demised at young ages from suspected cardiovascular causes. The same SDHB mutation, Class V variant c.724C>A p.(Arg242Ser), was detected in one of his asymptomatic siblings. As there is limited data describing hereditary PPGL syndromes in Africa this report of an SDHB associated PPGL is a notable contribution to the literature in this growing field. Due to the noteworthy clinical implications of PPGL mutations, it highlights the existing need for broader genetic screening amongst African patients with PPGL despite the limited healthcare resources available in this region.

Dutch founder SDHB exon 3 deletion in patients with pheochromocytoma-paraganglioma in South Africa

“…The study has a number of limitations. As a small single-center cohort, we cannot determine the overall structure of the genetic risk profile for endocrine neoplasias, including PPGL in South Africa as a whole, similar to previous genetic studies on this topic in South Africa ( 10 , 11 , 12 , 22 ). Hence, it remains to be proven in larger series whether the SDHB exon 3 deletion mutation plays a major role in PPGL risk nationally in South Africa.…”

“…Whereas other founder effects are well established in South Africa and most PPGL in the Netherlands are accounted for by founder SDHx mutations, to date, no Dutch founder effect has been demonstrated in PPGL patients in South Africa. Indeed, there is a general paucity of genetic risk information for PPGL and other endocrine-related cancers throughout sub-Saharan Africa ( 10 , 11 , 12 ). As part of a 2-year collaborative study, we examined the genetic causes of different endocrine and neuroendocrine tumors in a single center in South Africa.…”