Germline mutations and genotype–phenotype correlation in Asian Indian patients with pheochromocytoma and paraganglioma

Background Genetic aetiology of pheochromocytoma (PCC) and paraganglioma (PGL) is increasingly being studied; however, Asian Indian data on this aspect are scarce. Objective To study the prevalence of germline mutations and genotype–phenotype correlation in Asian Indian PCC/PGL patients. Design In this study, 150 index patients (M:F, 73:77) with PCC/PGL were evaluated. Phenotypic data were collected. Germline mutations in five susceptibility genes ( RET , VHL , SDHB , SDHD and SDHC ) were tested by sequencing and NF1 was diagnosed according to phenotype. Result Of the total population, 49 (32.7%) PCC/PGL patients had germline mutations ( VHL : 23 (15.3%), RET : 13 (8.7%), SDHB : 9 (6%), SDHD : 2 (1.3%) and NF1 : 2 (1.3%)). Amongst the 30 patients with familial and/or syndromic presentation, all had germline mutations ( VHL : 14 (46.7%), RET : 13 (43.3%), SDHB : 1 (3.3%) and NF1: 2 (6.7%)). Out of 120 patients with apparently sporadic presentation, 19 (15.8%) had a germline mutation ( VHL : 9 (7.5%), SDHB : 8 (6.7%) and SDHD : 2 (1.7%)). Mutation carriers were younger (29.9 ± 14.5 years vs 36.8 ± 14.9; P = 0.01) and had a higher prevalence of bilateral PCC (26.5% vs 2.9%, P < 0.001) and multifocal tumours (12.2% vs 0.96%, P = 0.06). Based on syndromic features, metastasis, location and number of tumours, around 96% mutations in our cohort could be detected by appropriately selected single gene testing. Conclusion Asian Indians with PCC/PGL differ from Western cohorts in having preponderance of VHL mutations in multifocal tumours and apparently sporadic unilateral PCC. Syndromic presentation, metastasis, location and number of PCC/PGL can be effectively used for guiding genetic prioritisation.