Genotype-phenotype correlation in paediatric pheochromocytoma and paraganglioma: a single centre experience from
Kranti Khadilkar1, Vijaya Sarathi2, Rajeev Kasaliwal3
1Department of Endocrinology, Seth G S Medical College and KEM Hospital, Mumbai.
Insights
Pediatric pheochromocytoma (PCC)/paraganglioma (PGL) patients show higher germline mutation rates, particularly VHL mutations, than adults. Early genetic screening, especially for VHL, is crucial for children with PCC/PGL.
Area of Science:
- Endocrinology
- Genetics
- Pediatric Oncology
Background:
- Limited data exists on genotype-phenotype correlations in pediatric pheochromocytoma (PCC) and paraganglioma (PGL).
- Understanding germline mutations in children with PCC/PGL is essential for diagnosis and management.
- Comparison with adult cohorts provides valuable insights into age-related differences.
Purpose of the Study:
- To investigate the prevalence of germline mutations in children with PCC/PGL.
- To determine genotype-phenotype correlations in pediatric PCC/PGL patients.
- To compare findings in children with a cohort of adult PCC/PGL patients.
Main Methods:
- Genetic testing for five PCC/PGL susceptibility genes (RET, VHL, SDHB, SDHD, SDHC) was performed on 121 pediatric patients (age ≤20).
- Clinical diagnosis of neurofibromatosis type 1 (NF1) was evaluated.
- Patients were compared to an adult PCC/PGL cohort.
Main Results:
- Germline mutations were found in 46.7% of pediatric patients, significantly higher than in adults (26.4%).
- VHL mutations were more common in children (33.3%) than adults (10.9%).
- Pediatric patients with VHL mutations showed increased rates of bilateral PCC, PCC with synchronous PGL (PCC+sPGL), and secondary PCC/PGL development.
Conclusions:
- All children diagnosed with PCC/PGL should undergo germline mutation screening.
- Priority should be given to VHL gene testing in pediatric PCC/PGL patients.
- Pediatric VHL mutation carriers require thorough evaluation for bilateral PCC and PCC+sPGL, with close follow-up for secondary tumor development.
Background:
Data on genotype-phenotype correlation in children is limited. Hence, we studied the prevalence of germline mutations and genotype-phenotype correlation in children with pheochromocytoma (PCC)/paraganglioma (PGL) and compared it with adult PCC/PGL cohort.
Methods:
A total of 121 consecutive, unrelated, index PCC/PGL patients underwent genetic testing for five PCC/PGL susceptibility genes (RET, VHL, SDHB, SDHD and SDHC) and were evaluated for clinical diagnosis of neurofibromatosis type1 (NF1).
Results:
Thirty patients (12 boys, 18 girls) presented at ≤20 years of age (mean age of 15.9±3.8 years). Children were more frequently symptomatic and more frequently had bilateral PCC than adults. Fourteen (46.7%) PCC/PGL children had germline mutations (VHL 10 [33.3%], SDHB 2 [6.6%], and SDHD 2 [6.6%]). Overall germline mutations (46.7% vs. 26.4%, p=0.04) and VHL mutations (33.3% vs. 10.9%, p=0.026) were significantly more common in children than in adults. In children with VHL mutations, bilateral PCC were more frequent than in adults with VHL mutations. Within the paediatric cohort, bilateral PCC (60% vs. 5%, p=0.002), PCC+sPGL (30% vs. 0%, p=0.03) and occurrence of a second PCC/PGL (30% vs. 0%, p=0.03) were significantly more frequent among children with VHL mutations than others.
Conclusions:
All PCC/PGL children should be screened for germline mutations with first priority for VHL gene testing. Paediatric PCC/PGL patients with VHL mutations should be thoroughly evaluated for bilateral PCC and PCC+sPGL at initial presentation and closely followed up for occurrence of a second PCC/PGL.
