Characteristics and genetic testing outcomes of patients with clinically suspected paraganglioma/pheochromocytoma (PGL/PCC) syndrome in Singapore

Kay Reen Ting,Samuel Ow Guan Wei,Pei Yi Ong,Soo-Chin Lee,Chin Meng Khoo,Rajeev Parameswaran,Doddabele Srinivasa Deepak

doi:10.1186/s13053-020-00156-9

Abstract

BackgroundHereditary paraganglioma (PGL) and pheochromocytoma (PCC) syndromes are rare conditions, with limited data on spectrum of causative gene variants of these syndromes in Asian patients.MethodsWe describe the clinical characteristics and genetic testing outcomes of patients with suspected hereditary PGL/PCC who were referred to a tertiary cancer genetics clinic in Singapore.ResultsAmong 2196 patients with suspected hereditary cancer syndrome evaluated at the cancer genetics clinic from 2000 to 2019, 13/2196 (0.6%) patients fulfilled clinical suspicion for hereditary PGL/PCC syndrome. After genetic counselling, 10 patients underwent multi-gene next generation sequencing and deletion/duplication analysis, including SDHAF2, SDHA, SDHB, SDHC, SDHD, VHL, NF1, RET, MAX, and TMEM127. Seven of 10 patients (70%) were identified to carry pathogenic variants, including 3 unrelated Chinese patients with head and neck PGL who carried the same SDHD: c.3G > C (p.Met1Ile) variant that was previously reported to be a possible founder variant in Chinese, and 3 patients with urogenital PGL and 1 patient with retroperitoneal PGL who carried different SDHB variants. Variant carriers were younger, more likely to present with multiple tumours, or have family history of paraganglioma or pheochromocytoma, than non- variant carriers.ConclusionHereditary PGL/PCC accounts for only 0.6% of patients seen in an adult cancer genetics clinic in Asia. SDHD and SDHB genes remain the most important causative genes of hereditary PGL/PCC in Asia even when patients are tested with multi-gene NGS panel.

Highlights

Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumours with incidence rate occurring around 2 to 8 cases per million person years [1, 2], affecting both genders and commonly occurring in the third to fifth decades of life
We describe a series of patients with suspected hereditary PGL/PCC syndrome who underwent multi-gene panel testing at a Cancer Genetics Program at an academic cancer centre in Singapore
Hereditary paraganglioma or pheochromocytoma syndromes are rare conditions, with fewer than 1% of patients who were referred to our adult cancer genetics clinic fulfilling clinical suspicion for hereditary PGL/ PCC

Summary

Introduction

Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumours with incidence rate occurring around 2 to 8 cases per million person years [1, 2], affecting both genders and commonly occurring in the third to fifth decades of life. Head and neck paragangliomas (HN-PGL) involve the skull base, neck and upper mediastinum; with the commonest site of tumour occurring above the bifurcation of carotid arteries. This group of paragangliomas are typically parasympathetic and nonsecretory. Majority of PGL/PCC are benign cases but approximately 10% of PCC and around 15–35% of extra-adrenal abdominal paragangliomas are malignant [4, 5]. Hereditary paraganglioma (PGL) and pheochromocytoma (PCC) syndromes are rare conditions, with limited data on spectrum of causative gene variants of these syndromes in Asian patients

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