Kasi Ajay S, Jurgensen Taryn J, Yen Stephanie, Kun Sheila S, Keens Thomas G, Perez Iris A
Division of Pediatric Pulmonology and Sleep Medicine, Children's Hospital Los Angeles, Los Angeles, California.
Keck School of Medicine of the University of Southern California, Los Angeles, California.
J Clin Sleep Med. 2017 Jul 15;13(7):925-927. doi: 10.5664/jcsm.6670.
non-polyalanine repeat mutation (NPARM) in patients with congenital central hypoventilation syndrome (CCHS) is generally considered to be associated with full-time ventilator dependence and severe autonomic nervous system dysfunction. We report a three-generation family with four individuals possessing a novel NPARM (c.245C > T) with variable phenotypes. This mutation was inherited in an autosomal dominant pattern with variable penetrance. The affected family members with CCHS have a milder phenotype than is typically expected with a NPARM. Two family members are ventilator dependent only during sleep and do not have Hirschsprung disease or neural crest tumors. One family member was asymptomatic until systemic hypertension developed during adulthood and another family member remains asymptomatic as an adult. Our findings emphasize the importance of monitoring adults with a NPARM who are considered asymptomatic in childhood.
先天性中枢性低通气综合征（CCHS）患者的非聚丙氨酸重复突变（NPARM）通常被认为与长期呼吸机依赖和严重的自主神经系统功能障碍有关。我们报告了一个三代家族，其中有四名个体携带一种具有可变表型的新型NPARM（c.245C>T）。这种突变以常染色体显性模式遗传，具有可变的外显率。患有CCHS的受影响家庭成员的表型比典型的NPARM预期的要轻。两名家庭成员仅在睡眠期间依赖呼吸机，且没有先天性巨结肠病或神经嵴肿瘤。一名家庭成员在成年期出现系统性高血压之前无症状，另一名成年家庭成员仍无症状。我们的研究结果强调了对儿童期被认为无症状的NPARM成年人进行监测的重要性。
