Phaeochromocytoma and paraganglioma (PPGL) syndromes associated with germline mutations are highly morbid. Published data has consistently demonstrated a high occurrence of tumours due to hereditary PPGL in childhood with a predominance of cluster 1 mutations (VHL and genes relating to the SDH complex). This cluster is associated with more aggressive features including bilateral, multiple and extra-adrenal tumours.1,2,3
As knowledge of these rare syndromes continues to develop and new implicated genes have only recently been discovered, data relating to hereditary PPGL has not been captured in the Australian Paediatric Cancer Registry. The findings of this study will therefore establish for the first time accurate prevalence of PPGL within this demographic within Australia. The outcomes will also give further insight into genotype-phenotype correlations and contribute to the body of evidence used to develop genotype-specific surveillance guidelines.
Objective: The retrospective element of this study established the prevalence of hereditary PPGL, including underlying genotype. Genotypes included VHL, SDHB, SDHD, SDHC, SDHA, RET, NF1, TMEM127 and MAX. In those patients who had not been exhaustively investigated to exclude a germline mutation, multi-gene panel testing was performed.
Methods: Information was collected through ‘TrakGene’. Patient characteristics included age at diagnosis, gender, clinical features. Tumours were classified by hormone secretion profile, tumour number, anatomical location, histological features and benign/malignant. Stored DNA was accessed for further testing, if appropriate.
Results(prelim): Results from a single centre identified 13 paediatric patients. 9 (69%) carried a germline pathogenic variant: 6 SDHB (of which 5 were extra-adrenal, 5 were multi-focal and 2 were metastatic) and 3 VHL.
Conclusions: PPGLs diagnosed in children and adolescents in Australia are likely to be associated with germline pathogenic variants in VHL or SDHB. These patients should be referred to specialist services for comprehensive perioperative work-up, detection of bilateral, multifocal or metastatic disease, and family counselling.