Genotype-phenotype correlations in paediatric and adolescent phaeochromocytoma and paraganglioma: a cross-sectional study.

Abstract

Phaeochromocytoma (PC) and paraganglioma (PGL) syndromes associated with germline pathogenic variants are associated with high morbidity and mortality. Establishing genotype-phenotype correlations within a young population is challenging due to their rare occurrence. To describe genotype-phenotype correlations in paediatric and adolescent patients diagnosed with PC/PGL. To establish the incidence of PC/PGL in a young population and prevalence of germline pathogenic variants within this group. We conducted a cross-sectional study of patients diagnosed with a PC/PGL aged 0-21 years old who were reviewed within Familial Cancer Services within New South Wales and the Australian Capital Territory, Australia. A germline pathogenic variant was detected in 80% (24/30) of patients; <i>SDHB</i>: n=12, <i>VHL</i>: n=11, and <i>MAX</i>: n=1. Only patients harbouring a germline pathogenic variant reported a family history of syndromic tumours, those with apparently sporadic disease did not (62.5% versus 0%, p=0.02). All patients with <i>VHL</i> presented with an adrenal tumour compared with 25% of those with <i>SDHB</i> (100% versus 25%, p=0.01). Occurrence of multiple primary PC/PGL was seen in patients with <i>VHL</i> however was absent in patients with <i>SDHB</i> (36% versus 0%, p=0.03). Incidence rate of paediatric PC/PGL was 0.45 cases per million person years. PC/PGL diagnosed in children and adolescents were strongly associated with germline pathogenic variants in <i>VHL</i> or <i>SDHB</i>. These patients should be referred to specialist services for family counselling and genetic testing along followed by investigations for the detection of bilateral, multifocal or metastatic disease, and lifelong surveillance for recurrent disease.