Hereditary Paraganglioma in an Omani Family

Abstract

Pheochromocytomas are tumors derived from chromaffin cells within the medulla of adrenal glands, whereas paragangliomas are tumors derived from extra-adrenal chromaffin cells of the sympathetic prevertebral and paravertebral ganglia. The growing deployment of genetic testing has shown that approximately 30% of pheochromocytoma and paraganglioma (PPGL) patients carry familial pathogenic germline mutations in known PPGL-susceptibility genes. This prompts genetic screening of their family members and leads to an increase in the detection of asymptomatic PPGLs or non-secreting tumors reported in familial cases discovered after the index patient work-up. Here, we present three case reports of affected members of a single Omani family with a history of paraganglioma and highly variable clinical presentations among the affected members. Eight out of the 16 siblings (50.0%) in the second generation of the reported family pedigree were carriers of the succinate dehydrogenase B:c.574T>C mutation, reflecting the autosomal dominant inheritance risk of paraganglioma and other associated tumors. This report highlights the complexity of managing such families and encourages further discussion regarding the management of asymptomatic PPGL-associated mutation carriers. Genetic screening has enabled the early detection of PPGLs, for which early surgical intervention can significantly impact prognosis and treatment strategies to reduce morbidity and mortality. Although PPGLs are similar tumors, they warrant distinction from each other with respect to their differences in locations, manifestations, secretory functions, genetic syndromes, and propensity to metastasize. While current guidelines are clear concerning symptomatic PPGL cases, the management of asymptomatic mutation carriers requires further elucidation.