First-positive surveillance screening in an asymptomatic SDHA germline mutation carrier. (30th May 2019)

• Record Type: Journal Article
• Authors: White, Gemma; Tufton, Nicola; Akker, Scott A
• Is Part Of: Endocrinology, diabetes & metabolism case reports. (2019)
• Publication Date: 2019-05-30
• Subjects: Adult -- Female -- White -- United Kingdom; Adrenal -- Tumours and neoplasia -- Metanephrines -- Normetanephrine -- Paraganglioma -- Carotid body paraganglioma; Cardiomyopathy -- MRI -- Metanephrines (urinary) -- Molecular genetic analysis -- Normetanephrine -- Methoxytyramine -- Genetic analysis; Neurology; New disease or syndrome: presentations/diagnosis/management -- May -- 2019; Endocrinology -- Periodicals; Diabetes -- Periodicals; Diabetes Mellitus; Endocrinology; Diabetes; Endocrinology; Case Reports; Periodicals; Periodicals; 616.4
• DOI: 10.1530/EDM-19-0005
• Languages: English
• ISSNs: 2052-0573

Abstract

Summary: At least 40% of phaeochromocytomas and paraganglioma's (PPGLs) are associated with an underlying genetic mutation. The understanding of the genetic landscape of these tumours has rapidly evolved, with 18 associated genes now identified. Among these, mutations in the subunits of succinate dehydrogenase complex ( SDH ) are the most common, causing around half of familial PPGL cases. Occurrence of PPGLs in carriers of SDHB, SDHC and SDHD subunit mutations has been long reported, but it is only recently that variants in the SDHA subunit have been linked to PPGL formation. Previously documented cases have, to our knowledge, only been found in isolated cases where pathogenic SDHA variants were identified retrospectively. We report the case of an asymptomatic suspected carotid body tumour found during surveillance screening in a 72-year-old female who is a known carrier of a germline SDHA pathogenic variant. To our knowledge, this is the first screen that detected PPGL found in a previously identified SDHA pathogenic variant carrier, during surveillance imaging. This finding supports the use of cascade genetic testing and surveillance screening in all carriers of a pathogenic SDHA variant. Learning points: SDH mutations are important causes of PPGL disease. SDHA is much rarer compared to SDHB and SDHD mutations. Pathogenicity and penetrance are yet to be fully determined in cases of SDHA -related PPGL. Surveillance screening should be used for SDHA PPGL cases to identify recurrence, metastasis or metachronous disease. Surveillance screening for SDH -related disease should be performed in identified carriers of a pathogenic SDHA variant.