MON-380 Tinnitus with Unexpected Spanish Roots: Head and Neck Paragangliomas Caused by SDHAF2 Mutation

Abstract

Introduction: Head and neck paragangliomas (HNPGL) are a subtype of pheochromocytoma/paraganglioma (Pheo/PGL) that originate from the autonomuos nervous system. In contrast to abdominal and thoracic Pheo/PGL, HNPGL are usually non-secretory, of parasympathetic origin and metastasize only rarely. Although HNPGL may occur as sporadic tumors, it is estimated that up to 40% of all cases may have a hereditary background that impacts therapeutic strategies, follow-up of affected patients and diagnostic approaches of family members. The most common mutations are found in the succinate dehydrogenase (SDH) genes with the highest prevalence of mutations in SDH-D, followed by SDH-B and SDH-C. Clinical case: A 15 year old male patient presented with tinnitus and hearing loss of the left ear. Imaging revealed a left sided jugulotympanic tumor (33x34mm) and a tumor of the right carotid body (12x15mm). The patient was normotensive, did not report on spells and plasma free metanephrine/catecholamine were not elevated. The morphological suspicion of a paraganglioma was confirmed histologically following resection of the jugulotympanic lesion. Immunohistochemistry showed a loss of SDHB-expression and genetic testing (somatic and germline) revealed a mutation in the SDH assembly factor 2 (SDHAF2) gene (c.232G>A). The patient's father is of Spanish descent. There was no family history for tumors. The hereditary paraglioma syndrome 2 (PGL2) has first been described in 1982 in a Dutch and later in a Spanish family and was found to be caused by a mutation in the SDHAF2 gene. SDHAF2 is a highly conserved co-factor involved in the flavination of the SDH-A subunit. The inheritence is autosomal dominant with maternal imprinting, leading to tumorigenesis only by paternal transmission. This may explain the seemingly negative family history. As in our case, patients with PGL2 usually present at young age with multiple, benign and non-secretory HNPGL. The penetrance reaches 88-100% by the age of 50 years. Conclusion: Our findings emphasize the relevance of genetic testing in patients with HNPGL, also with negative family history, especially when the patients present at young age and with multiple lesions.