Endocrine Abstracts

Introduction:The genetics of most cases of familial phaechromocytomas is unknown.

Up to 50%of paragangliomas are

familial and increased susceptibility is seen in SDHD and SDHC mutations.

We report a family with a mutation in the SDHB gene .

Case report: The index case, a 22 year old male was treated at the age of 10 years with extra adrenal phaeochromocytoma. Recently, he was found to have a glomus jugulare tumour with multiple cranial nerve palsies.

The proband's mother had a glomus jugulare tumour excised 10 years ago. She is being screened annually for recurrence as well as for a phaeochromocytoma.

DNA analysis of the proband and his mother excluded germline mutations in VHL, SDHD, and in MEN 2 associated regions of the RET gene. Sequence analysis of the SDHB gene revealed a C to T transition and nucleotide 402 resulting in an arginine residue at position 91 being replaced by a termination codon as reported by Astuti et al (2001).

The remaining family member, the proband's sister was also tested and has the SDHB mutation and is under regular surveillance.

Discussion: The majority of nonsyndromic familial phaeochromocytomas do not have a well defined molecular basis. Astuti et al1 studied familial and sporadic cases of phaeochromocytoma. They identified inactivating SDHB mutations in 2/5 kindreds with familial phaeochromocytoma, 2/3 kindreds with phaeochromocytoma and paraganglioma and 1/24 cases of sporadic phaeochromocytoma.

This case highlights the importance of obtaining information about family history in individuals presenting with phaeochromocytoma and the need to consider DNA analysis in individuals where more than one family member is affected or where a relative has had a paraganlgioma.

References:

1. Astuti D, Latif F, Dallol A, Dahia PLM, Douglas F, George E, Skoldberg F, Husebye ES, Eng C, Maher

ER. Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Am J Hum Genet 2001; 69:49-54