A Full Phenotype of Paraganglioma Linked to a Germline SDHB Mosaic Mutation.

Context: Heterozygous germline pathogenic variants found in succinate dehydrogenase (SDH) complex genes predispose to hereditary paraganglioma (PGL) syndromes. No mosaicism has yet been reported in this setting.

Design And Participant: We describe the clinical history of a case of SDH complex, subunit B (SDHB) mosaicism. A 24-year-old woman who developed a cardiogenic shock during dental surgery was diagnosed with a functional para-aortic PGL, which produced predominantly norepinephrine and its metabolites. The tumor was removed and showed a loss of SDHB expression by immunohistochemistry. Four years after initial laparotomy, the patient had a rapid cardiac decompensation during her second pregnancy, despite negative imaging 10 months before. Two recurrent functional PGLs were found and surgically removed. Initial genetic analysis performed by Sanger sequencing did not reveal any germline pathogenic variant in SDHB, VHL, SDHD, SDHC, SDHAF2, RET, MAX, and TMEM127. Next-generation sequencing performed on tumor- and blood-extracted DNAs highlighted the presence of a mosaic rare variant in SDHB (c.557G>A, p.Cys186Tyr) with an allelic ratio of 15% in the blood DNA.

Conclusions: We report the full clinical description of a proband with SDHB mosaicism associated with a functional, recurrent PGL. This case strengthens the necessity to complete the genetic analysis with methodologies able to identify germline mosaicism, especially in the case of early disease onset.