Pambinezhthu Fathima, Hamza Nishath, Al Kharusi Manal, Ramadhan Fatma, Al Busaidi Noor, Kamona Atheel
National Diabetes and Endocrinology Centre, Royal Hospital, Muscat, Oman.
National Genetic Centre, Royal Hospital, Muscat, Oman.
Oman Med J. 2021 Jan 31;36(1):e229. doi: 10.5001/omj.2021.10. eCollection 2021 Jan.
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.
嗜铬细胞瘤是起源于肾上腺髓质嗜铬细胞的肿瘤，而副神经节瘤是起源于交感神经节前和椎旁神经节肾上腺外嗜铬细胞的肿瘤。基因检测的日益广泛应用表明，约30%的嗜铬细胞瘤和副神经节瘤（PPGL）患者在已知的PPGL易感基因中携带家族性致病种系突变。这促使对其家庭成员进行基因筛查，并导致在索引患者检查后发现的家族性病例中，无症状PPGL或非分泌性肿瘤的检出率增加。在此，我们报告了一个阿曼家族中受影响成员的三例病例，该家族有副神经节瘤病史，且受影响成员的临床表现高度可变。在报告的家族谱系第二代的16名兄弟姐妹中，有8名（50.0%）是琥珀酸脱氢酶B:c.574T>C突变的携带者，这反映了副神经节瘤和其他相关肿瘤的常染色体显性遗传风险。本报告强调了管理此类家族的复杂性，并鼓励进一步讨论无症状PPGL相关突变携带者的管理。基因筛查能够早期发现PPGL，早期手术干预对其预后和治疗策略有显著影响，可降低发病率和死亡率。虽然PPGL是相似的肿瘤，但它们在位置、表现、分泌功能、遗传综合征和转移倾向方面的差异值得相互区分。虽然目前的指南对有症状的PPGL病例很明确，但无症状突变携带者的管理需要进一步阐明。
