Khadilkar Kranti, Sarathi Vijaya, Kasaliwal Rajeev, Pandit Reshma, Goroshi Manjunath, Shivane Vyankatesh, Lila Anurag, Bandgar Tushar, Shah Nalini S
Department of Endocrinology, Seth G S Medical College and KEM Hospital, Mumbai.
Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Center, Bangalore.
J Pediatr Endocrinol Metab. 2017 May 1;30(5):575-581. doi: 10.1515/jpem-2016-0375.
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.
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).
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.
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.
儿童基因型-表型相关性的数据有限。因此，我们研究了嗜铬细胞瘤（PCC）/副神经节瘤（PGL）患儿种系突变的患病率及基因型-表型相关性，并将其与成人PCC/PGL队列进行比较。
共121例连续、无亲缘关系的PCC/PGL索引患者接受了5个PCC/PGL易感基因（RET、VHL、SDHB、SDHD和SDHC）的基因检测，并对1型神经纤维瘤病（NF1）进行了临床诊断评估。
30例患者（12例男孩，18例女孩）年龄≤20岁（平均年龄15.9±3.8岁）。与成人相比，儿童出现症状的频率更高，双侧PCC的发生率也更高。14例（46.7%）PCC/PGL患儿存在种系突变（VHL 10例[33.3%]，SDHB 2例[6.6%]，SDHD 2例[6.6%]）。总体而言，种系突变（46.7%对26.4%，p=0.04）和VHL突变（33.3%对10.9%，p=0.026）在儿童中比在成人中更为常见。在携带VHL突变的儿童中，双侧PCC比携带VHL突变的成人更常见。在儿科队列中，携带VHL突变的儿童双侧PCC（60%对5%，p=0.002）、PCC+sPGL（30%对0%，p=0.03）以及出现第二个PCC/PGL（30%对0%，p=0.03）的频率显著高于其他儿童。
所有PCC/PGL患儿均应筛查种系突变，优先进行VHL基因检测。携带VHL突变的儿科PCC/PGL患者在初次就诊时应全面评估双侧PCC和PCC+sPGL情况，并密切随访是否出现第二个PCC/PGL。
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