Paragangliomas are rare tumors and seldom cause endocrine hypertension. Germline mutations in the succinate dehydrogenase subunit B gene (SDHB) have been associated with malignant paragangliomas. We report a family with nonclassic congenital adrenal hyperplasia (CAH) in whom one member suffered from metastatic paraganglioma. A 13-year-old boy presented with delayed puberty, nocturnal enuresis, and headaches. His laboratory test results, including thyroid and adrenal tests, were within normal limits. MRI of the brain showed a lesion in the diploic space in the frontal region. CT of his head revealed a lytic bone lesion considered to likely be a histiocytic eosinophilic granuloma. A bone scan showed another lytic lesion in the right proximal femur. Bone biopsy of the skull lesion identified a paraganglioma, likely metastatic. Further imaging showed a 8 × 3 × 3 cm mass close to the vena cava and aorta. Blood pressure of this patient was normal; 24-hour urinary norepinephrine was slightly elevated, and he received preoperative therapy. After surgical tumor removal, postoperative MIBG showed persistent uptake in the abdomen and right femur. His sister was diagnosed to have 3-β-dehydrogenase deficiency; his grandmother had a pituitary adenoma. Germline mutation analysis of the SDHB gene, located at 1p36.13, revealed a known missense mutation (C.418G>T) and a previously unreported splice donor region DNA sequence variation in intron 2 (C.200+7A>G) in the index patient. His sister and father were heterozygous for this splice donor variation, whereas his mother was heterozygous for the known missense mutation. Whole-body imaging of the sister with nonclassic CAH was within normal limits. This case illustrates that malignant paragangliomas can occur in children and are associated with germline sequence variants in the SDHB gene. Clinical presentation may mimic histiocytosis and may include delayed puberty. The combination of sequence variations in the SDHB gene in the same patient may trigger tumor growth of selected chromaffin cells.
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