Germline mutations in, a.o., subunits B and D of the succinate dehydrogenase (SDH) gene are significant causes of inherited paragangliomas (PGLs) and distinct genotype-phenotype associations have been described. Although malignant disease seems largely associated with SDHB-mutations, the actual risk of developing malignant PGL in SDHB– and SDHD-mutation carriers is subject of debate.
To provide newly identified mutation carriers with more accurate prognostic information, we performed a systematic review and meta-analysis on the risk of developing malignant PGLs in SDHB– and SDHD-mutation carriers. Our results show that incidence and prevalence of malignant PGLs are higher in SDHB– than in SDHD-mutation carriers, but lower in SDHB-mutation carriers than hitherto appreciated. (By Dr. Leonie van Hulsteijn, http://jmg.bmj.com/content/early/2012/10/24/jmedgenet-2012-101192 )