PDF(Pubmed)
Abstract：
Congenital central hypoventilation syndrome (CCHS) is a disorder of ventilatory control and autonomic dysregulation that can be caused by mutations in the paired-like homeobox 2B (PHOX2B) gene. The majority of CCHS cases are caused by polyalanine repeat mutations (PARMs) in PHOX2B; however, in rare cases, non-polyalanine repeat mutations (NPARMs) have been identified. Here, we report two patients with NPARMs in PHOX2B. Patient 1 has a mild CCHS phenotype seen only on polysomnogram, which was performed for desaturations and stridor following a bronchiolitis episode, and characterized by night-time hypoventilation and a history of ganglioneuroblastoma. She carried a novel de novo missense variant, p.R102S (c.304C > A), in exon 2. Patient 2 has an atypical CCHS phenotype including micrognathia, gastroesophageal reflux, stridor, hypopnea, and intermittent desaturations. Sleep study demonstrated that Patient 2 had daytime and night-time hypercarbia with obstructive sleep apnea, requiring tracheostomy. On PHOX2B sequencing, she carried a recently identified nonsense variant, p.Y78* (c.234C > G), in exon 1. In summary, we present two patients with CCHS and identified NPARMs in PHOX2B who have distinct differences in phenotype severity, further elucidating the range of clinical outcomes in CCHS and illustrating the necessity of considering PHOX2B mutations when encountering atypical CCHS presentations.
摘要：
先天性中枢性通气不足综合征（CCHS）是一种通气控制和自主神经失调的疾病，可能是由配对同源异型盒2B（PHOX2B）基因突变引起的。大多数CCHS病例是由PHOX2B中的多丙氨酸重复突变（PARM）引起的；然而，在极少数情况下，已鉴定出非多丙氨酸重复突变（NPARM）。这里,我们报告了两名患有PHOX2B的NPARMs患者。患者1具有仅在多导睡眠图上可见的轻度CCHS表型，这是针对毛细支气管炎发作后的去饱和和喘鸣进行的，以夜间通气不足和神经节神经母细胞瘤病史为特征。她携带了一部小说，p.R102S（c.304C>A），在外显子2中。患者2具有非典型的CCHS表型，包括小颌畸形，胃食管反流,stridor,呼吸不足,和间歇性去饱和。睡眠研究表明，患者2有白天和夜间高碳酸血症伴阻塞性睡眠呼吸暂停，需要气管造口术.在PHOX2B测序中，她携带了一个最近发现的废话变体，p.Y78*（c.234C>G），在外显子1。总之,我们介绍了两名CCHS患者，并鉴定了PHOX2B中的NPARMs，这些患者在表型严重程度上有明显差异，进一步阐明CCHS的临床结局范围,并说明在遇到非典型CCHS表现时考虑PHOX2B突变的必要性.
