Multifocal Paraganglioma and Pheochromocytoma Due to Truncated SDHD Mutation

Pheochromocytoma and paraganglioma (PPGL) are rare autosomal dominant disorders derived from the neural crest chromaffin tissues of the autonomic nervous system. The succinate dehydrogenase complex subunit D (SDHD) gene has been implicated as one of the pathogenic genes. Although more than 100 SDHD mutations have been reported, the phenotype-genotype association remains unclear.

We reported a case of a patient who presented with multifocal PPGLs and with a rare SDHD mutation, and reviewed the phenotype-genotype association of SDHD.

We identified a pathogenic variant of SDHD (c.170-1G>T, NM_003002.3), which caused the complete deletion of exon 3 in the transcript and resulted in a shorter and unstable SDHD mRNA. And truncated SDHD mutations were prone to cause multifocal PPGL, whereas missense SDHD mutations usually caused unifocal lesions.

This is the first report linking the c.170-1G>T variant to multifocal tumors. We recommend whole-body imaging examinations and close, regular follow-up for these patients, given the risk of multifocal tumor development.