Sporadic paraganglioma caused by de novo SDHB mutations in a 6-year-old girl

Germline mutations in the succinate dehydrogenase complex subunit B (SDHB) gene (SDHB) cause susceptibility to paragangliomas and pheochromocytomas; however, it is exceedingly rare in childhood and especially in sporadic cases. We report the first Japanese pediatric case of paraganglioma with a de novo mutation in the SDHB gene. A 6-year-old girl with convulsions and hypertension was found to have a paravertebral abdominal tumor. Urinary and blood examinations revealed markedly elevated levels of norepinephrine. Following treatment for hypertension, the tumor was removed completely and histological findings were consistent with paraganglioma. Immunohistochemistry studies demonstrated the absence of SDHB protein expression, indicating an underlying SDH mutation with high probability. Germline mutation analysis of the SDHB gene revealed a heterozygous splice site mutation in intron 4 (C.423 + 1G > A). Subsequently, a second somatic genetic change was confirmed by multiplex ligation-dependent probe amplification (MLPA) analysis, showing that deletion of the wild-type allele resulted in loss of function of SDHB. No germline mutations in SDHB were detected in her parents. Conclusion: Genetic testing should be considered for pediatric patients with paragangliomas, even in the absence of familial history, as closer lifelong screening to detect the development of malignancy will be required for patients with SDHB mutations.What is Known• Most sporadic cases of paraganglioma with SDHB mutations occur between adolescence and adulthood.• Screening methods for carriers of SDHB mutations assessing recurrence and detecting developing metastases are yet to be standardized.What is New• The current case of an extra-adrenal paraganglioma with a de novo SDHB mutation had an onset at 6 years.• We suggest much closer periodical observation for these high-risk children.