Respiratory Unit, Academic Department of Pediatrics, Bambino Gesù Children's Hospital, IRCCS, Piazza di Sant'Onofrio 4, 00165, Rome, Italy.
Laboratory of Medical Genetics, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Ital J Pediatr. 2019 Apr 18;45(1):49. doi: 10.1186/s13052-019-0636-8.
Congenital central hypoventilation syndrome (CCHS) is characterized by alveolar hypoventilation increasing during sleep and affected patients are unable to perceive and respond to hypercarbia with increased ventilation and arousal during sleep. PHOX2B gene mutations are considered as responsible for CCHS. Most of patients with CCHS are heterozygous for polyalanine expansion mutations (PARMs) in exon 3, but 10% of patients with classic CCHS are heterozygous for non-polyalanine expansion mutations (NPARMs) of the PHOX2B gene.
Data are collected on 3 patients affected by CCHS who referred to the Paediatric Pulmonology Unit of Bambino Gesù Children's Hospital (Rome, Italy) for a multidisciplinary follow-up program between 2000 and 2017.
We describe three cases of patients affected by CCHS for which two novel mutations on exon 3 of PHOX2B gene were detected.
The description of these novel mutations and related clinical phenotypes allows to expand the knowledge into NPARM spectrum. Since the presence of Hirschsprung disease is related to NPARMs and the number of alanine repeats, we suggest performing CCHS genetic investigation and periodical assessment also in patients without a clear history of CCHS but affected by Hirschsprung disease.
Data are retrospectively collected.
先天性中枢性肺泡换气不足综合征（CCHS）的特征是肺泡换气在睡眠期间增加，并且受影响的患者在睡眠期间无法感知和响应高碳酸血症，并增加通气和觉醒。PHOX2B 基因突变被认为是 CCHS 的原因。大多数 CCHS 患者的第 3 外显子存在多聚丙氨酸扩展突变（PARMs），但 10%的经典 CCHS 患者存在 PHOX2B 基因的非多聚丙氨酸扩展突变（NPARMs）。
我们收集了 2000 年至 2017 年期间在意大利罗马 Bambino Gesù 儿童医院儿科肺病科接受多学科随访的 3 例 CCHS 患者的数据。
我们描述了 3 例 CCHS 患者的病例，在 PHOX2B 基因的第 3 外显子上检测到了两个新的突变。
这些新突变及其相关临床表现的描述扩展了 NPARM 谱的知识。由于巨结肠病与 NPARMs 和丙氨酸重复数有关，因此我们建议对没有明确 CCHS 病史但患有巨结肠病的患者进行 CCHS 基因检测和定期评估。
数据是回顾性收集的。
