Uncharted territory: a novel SDHC mutation in a young patient with paraganglioma

Vasiliki Siampanopoulou; Emmanouela Linardaki; Petros Papalexis; Alexandros-Aristeidis Lafioniatis; Georgia Tsirou; Varvara Chalmatzi; Constantine Stratakis; Anna Angelousi

doi:10.1530/endoabs.110.EP78

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Endocrine Abstracts (2025) 110 EP78 | DOI: 10.1530/endoabs.110.EP78

ECEESPE2025 ePoster Presentations Adrenal and Cardiovascular Endocrinology (170 abstracts)

Uncharted territory: a novel SDHC mutation in a young patient with paraganglioma

Vasiliki Siampanopoulou ¹ , Emmanouela Linardaki ² , Petros Papalexis ¹ , Alexandros-Aristeidis Lafioniatis ¹ , Georgia Tsirou ¹ , Varvara Chalmatzi ¹ , Constantine Stratakis ² & Anna Angelousi ¹

Author affiliations

¹Endocrinology Unit, First Internal Medicine Department, Laiko General Hospital of Athens, National and Kapodistrian University of Athens, Athens, Greece; ²Human Genetics & Precision Medicine, DIGENIA & EDIMO, Institute of Molecular Biology and Biotechnology of the Foundation for Research and Technology Hellas (IMMB-FORTH), Heraklion, Greece

JOINT1072

Introduction: Paragangliomas are rare neuroendocrine tumours of the sympathetic or parasympathetic ganglia that have a strong genetic predisposition. Mutations of the succinate dehydrogenase (SDHx) genes are most commonly involved and transmitted in an autosomal dominant manner.

Objective: We present the case of a 23-year-old female patient who was referred to our department for hoarseness and a palpable mass in the neck. Magnetic resonance imaging (MRI) revealed a 37x17x36 mm lesion involving the right carotid space, while the 68-Gallium-DOTATATE scan that followed unveiled a strong enhancement of the described mass (SUVmax=18, SUVliver=7). Urine and plasma metanephrines/normetanephrines levels were negative for catecholamine excess. The lesion was removed surgically, and the histology report confirmed the presence of a right carotid body paraganglioma.

Methods: Germline testing was pursued through a 50-cancer gene panel following genetic counselling.

Results: Genetic testing revealed a SDHC likely pathogenic variant (c.2T>G p.Met1?)in a heterozygous state, causing a substitution in exon 1 of the SDHC gene, which disrupts the initiation (start) site of the coding for the SDHC RNA that probably leads to not expressing the corresponding protein from the mutant allele, consistent with SDHC haploinsufficiency. This specific variation (chr1:161284197) has not been referred before in the gnomAD database, however, five other variants in the same coding area are listed in the CliVar database as pathogenic and related to paragangliomas. This patient was also a carrier of an SPG11 gene mutation (c.1471-1472delCT) which is associated with hereditary spastic paraplegia (HSP) in the homozygous states. Currently, no direct link has been found between these two gene mutations, as the first involves disruption of central to mitochondrial energy metabolism and the latter disorders in axonal maintenance and endosomal-lysosomal transport of neurons. The genetic analysis of the parents is pending.

Conclusion: Genetic analysis plays a vital role in the diagnosis and management of patients with paragangliomas. Clinically relevant variants can not only help establish genotype-phenotype correlations but also may identify asymptomatic family members.