Growth hormone deficiency in megalencephaly-capillary malformation syndrome: An association with activating mutations in PIK3CA
Growth hormone deficiency in megalencephaly-capillary malformation syndrome: An association with activating mutations in PIK3CA
复制标题
DOI：
10.1002/ajmg.a.61403
复制
发表时间：
2019-11-15
影响因子：
2
通讯作者：
Mirzaa, Ghayda
中科院分区：
文献类型：
--
作者：
Davis, Shanlee;Ware, Meredith A.;Mirzaa, Ghayda
巨脑毛细血管畸形综合征 (MCAP) 是一种大脑过度生长性疾病，其特征是皮质畸形（特别是多小脑回）、血管异常和继发于 PI3K-AKT-MTOR 通路 (PIK3CA) 体细胞激活突变的节段性过度生长。 MCAP 患者出现生长障碍和低血糖的病例已有报道，这引起了人们对生长激素 (GH) 缺乏症的怀疑。在此，我们报告了一项针对 MCAP 和 GH 缺乏儿童的观察性多中心研究。 11 名参与者被证实患有 GH 缺乏症，所有参与者的胰岛素样生长因子 1 和胰岛素样生长因子结合蛋白 3 的循环浓度都非常低或检测不到。七人接受了 GH 刺激测试，所有反应均不充分，其中 GH 峰值中值为 3.7 ng/ml（范围 1.1-8.6）。生长模式显示，在生命的第一年内，身长 z 值急剧下降，但随后趋于稳定。其中五人接受了 GH 治疗；其中一位因无法安慰而终止。其他四名参与者继续服用 GH，线性生长速度有所改善。该队列的 11 名参与者中有 7 名发现了其他内分泌疾病。这项研究表明，GH 缺乏与 MCAP 相关，患有 MCAP 和低血糖和/或出生后生长障碍的儿童应评估 GH 缺乏和其他内分泌疾病。
Megalencephaly-capillary malformation syndrome (MCAP) is a brain overgrowth disorder characterized by cortical malformations (specifically polymicrogyria), vascular anomalies, and segmental overgrowth secondary to somatic activating mutations in the PI3K-AKT-MTOR pathway (PIK3CA). Cases of growth failure and hypoglycemia have been reported in patients with MCAP, raising the suspicion for unappreciated growth hormone (GH) deficiency. Here we report an observational multicenter study of children with MCAP and GH deficiency. Eleven participants were confirmed to have GH deficiency, all with very low or undetectable circulating concentrations of insulin-like growth factor-1 and insulin-like growth factor binding protein-3. Seven underwent GH stimulation testing and all had insufficient responses with a median GH peak of 3.7 ng/ml (range 1.1-8.6). Growth patterns revealed a drastic decline in length z-scores within the first year of life but then stabilized afterward. Five were treated with GH; one discontinued due to inconsolability. The other four participants continued on GH with improvement in linear growth velocity. Other endocrinopathies were identified in 7 of the 11 participants in this cohort. This study indicates that GH deficiency is associated with MCAP and that children with MCAP and hypoglycemia and/or postnatal growth failure should be evaluated for GH deficiency and other endocrinopathies.