A novel succinate dehydrogenase subunit B gene mutation, H132P, causes familial malignant sympathetic extraadrenal paragangliomas.

We report a family with malignant sympathetic paragangliomas (PGL) exhibiting a new type of germline mutation in the succinate dehydrogenase subunit B (SDHB) gene. Two affected brothers, presenting with symptoms at the ages of 25 and 52 yr, suffered from malignant abdominal extraadrenal sympathetic PGL. They died of their disease at ages 43 and 61 yr. Their mother had the same history of signs and symptoms, suggesting a catecholamine-producing tumor at the age of 55 yr. Analysis of the germline DNA from these three patients revealed a novel mutation in exon 4 (H132P) of the SDHB gene. This mutation was absent in 160 control chromosomes. Loss of heterozygosity analysis of the tumors showed a loss of one SDHB allele, and RT-PCR-based expression analysis confirmed the exclusive expression of the mutated allele in both tumors. A review of the published PGL families revealed malignant tumors in seven of 12 well-documented families with SDHB mutation-associated extraadrenal PGL. These findings, as well as findings of the family reported here, suggest a strong causal relationship of SDHB germline mutations with malignant extraadrenal abdominal PGL and imply the necessity of a close follow-up of affected individuals and family members.

Great saphenous vein stripping with liberal use of subfascial endoscopic perforator vein surgery (SEPS).

This study is based on a unique registry of 632 patients who underwent great saphenous vein (GSV) stripping and liberal use of subfascial endoscopic perforator vein surgery (SEPS) for minimal to severe lower limb venous insufficiency. Clinical examinations and color-coded duplex scanning were performed on a randomly selected, manageable sample of 170 limbs to assess the affect of early SEPS on junctional (saphenofemoral [SFJ] and/or saphenopopliteal [SPJ]) and perforator vein (PV) insufficiencies and superficial varicosities at a median of 6.5 years. PV incompetence was present in 68 legs (40%), as the sole transfascial insufficiency in 28 limbs and combined with SFJ or SPJ incompetence in 40 limbs. Junction incompetence alone characterized an additional 38 limbs, bringing the total transfascial insufficiency prevalence to 62%. Superficial varicosities affected 46% of limbs. Overall CEAP clinical class was unimproved beyond preoperative values. PV incompetence was associated with higher CEAP and clinical venous severity scores than were junctional insufficiencies alone. We concluded that PV incompetence alone or combined with junctional insufficiency is associated with increased symptoms and disease progression. The prevalence of SFJ, SPJ, and PV incompetence (62%) and recurrent varicosities (46%) suggests that early use of SEPS does not prevent disease progression and offers no benefit over GSV stripping in the absence of deep vein insufficiency or threatened ulceration.