SDHD mutations in carotid body tumors and pheochromocytomas: paraganglioma syndrome type 1

摘要

The succinyldehydrogenase subunit D gene (SDHD gene) is a newly recognized susceptibility gene for adrenal pheochromocytoma, extra-adrenal abdominal and thoracic paraganglioma, and skull basis and neck paraganglioma, known as the paraganglioma syndrome type 1 (PGL1). The SDHD gene is located on chromosome 11q22.3-2.3 and consists of 4 exons. The mutations are spread randomly over all exons and include single amino acid changes and truncations of the gene product by stop codons, deletions, insertions or splice site alterations. Inheritance follows an autosomal-dominant pattern, but tumors occur only in descendents of fathers carrying the mutation which is consistent with maternal imprinting of the SDHD gene. Patients become symptomatic in the 2nd to 6th decade of life. Major tumor sites are the adrenal medulla and the carotid body. Malignancy is very rare. Treatment of PGL1 is a great challenge and requires abdominal, ENT and thoracic surgery, which should be performed in an atraumatic and whenever possible endoscopic and adrenal-sparing fashion.