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Case report of a man with multiple paragangliomas and pathogenic germline variants in both NF1 and SDHD

2021; Elsevier BV; Volume: 256-257; Linguagem: Inglês

10.1016/j.cancergen.2021.05.008

2210-7770

Prodromos Chatzikyriakou, Philip Touska, Mufaddal Moonim, Rupert Obholzer, Shazia Afridi, Ann Sandison, Rebecca J. Oakey, Louise Izatt,

Hormonal Regulation and Hypertension

• Patient with NF1 disease presented with multifocal head and neck paragangliomas . • Further genetic analysis to investigate his clinical phenotype identified a second paraganglioma-predisposing pathogenic variant in SDHD . • This is the first report of a case with NF1 disease and a concurrent pathogenic variant in another paraganglioma-predisposing gene. • Tumor exhibited cardinal features of SDH-related disease (loss of both 11p15 and of SDHB staining with DNA hypermethylation) but no loss-of-heterozygosity of SDHD . We report a novel case of multiple paragangliomas in a patient who was identified with pathogenic variants in both NF1 and SDHD genes. The proband is a man with known familial NF1 disease, diagnosed clinically in childhood. Multiple head and neck paragangliomas (HNPGL) were found during investigations for acute left sided neurological symptoms, in the region of his known plexiform neurofibroma. He was referred for genetic counselling. He underwent surgery to remove a left carotid body tumor (CBT). A pheochromocytoma and paraganglioma gene panel was tested. Blood and HNPGL tumor DNA were analyzed by whole exome sequencing. In addition to the NF1 truncating variant c.5107delA, p.(Ser1703AlafsTer7), the SDHD truncating pathogenic variant c.3G > A, p.(Met1?) was found. Tumor sequencing showed no LOH of SDHD or NF1 , but monoallelic loss of 11p15 and 11q12.2-q12.3 was observed. Co-occurrence of pathogenic variants in multiple cancer susceptibility genes is rare but possible, identified by the increased use of panel testing. This is the first description of a patient presenting with NF1 and SDHD dual pathology, with HNPGL development due to SDHD . This case illustrates the central role of genetic sequencing in PPGLs and the strong genotype-phenotype correlations of different genes.