Rush University Children's Hospital, Rush University Medical Center, Chicago, Illinois.
Northwestern University, Northwestern Memorial Hospital, Chicago, Illinois.
J Clin Sleep Med. 2020 Jun 15;16(6):977-982. doi: 10.5664/jcsm.8434.
Children with rare genetic diseases that cause respiratory dysregulation are at particularly high mortality risk due to development of respiratory failure. The tectonin β-propeller-containing protein 2 (TECPR2) mutations are proposed to cause autophagy defect affecting axonal integrity and development of progressive neurodegenerative and neuromuscular disease. Published TECPR2 mutation cases have described a high prevalence of respiratory failure. We review respiratory pathology in previously published cases and a new case of a 5-year-old girl with previously undescribed TECPR2 mutation demonstrating progressive central apnea due to respiratory cycle dysregulation. This is the first TECPR2 mutation case to demonstrate an ataxic (Biot's) breathing pattern with consistently inconsistent inspiratory and expiratory times and with relatively intact chemoreception during sleep. Therefore, we propose that the central apnea index alone may not be the appropriate marker for mortality risk. Rather, the morbidity and mortality associated with TECPR2 mutations are multisystem in nature and this burden complicates the ultimate needs for ventilation support and prognosis.
患有导致呼吸调节障碍的罕见遗传性疾病的儿童,由于呼吸衰竭的发展,死亡率极高。据推测, tectonin β- 螺旋蛋白包含蛋白 2(TECPR2)突变会导致自噬缺陷,影响轴突完整性和进行性神经退行性和神经肌肉疾病的发展。已发表的 TECPR2 突变病例描述了呼吸衰竭的高患病率。我们回顾了先前发表的病例中的呼吸病理学和一个新的 5 岁女孩的病例,该女孩存在以前未描述的 TECPR2 突变,表现为由于呼吸周期调节障碍导致进行性中枢性呼吸暂停。这是第一个显示共济失调(Biot's)呼吸模式的 TECPR2 突变病例,其吸气和呼气时间始终不一致,并且在睡眠期间相对完整的化学感受。因此,我们提出,单纯的中枢性呼吸暂停指数可能不是死亡率风险的适当标志物。相反,TECPR2 突变相关的发病率和死亡率在性质上是多系统的,这种负担使通气支持和预后的最终需求变得复杂。