Texas Children's Hospital, Houston, TX, USA.
Baylor College of Medicine, Houston, TX, USA.
Eur J Pediatr. 2021 Feb;180(2):469-473. doi: 10.1007/s00431-020-03848-5. Epub 2020 Oct 28.
Congenital central hypoventilation syndrome (CCHS) is an autonomic nervous system dysfunction due to PHOX2B gene mutation. Little is known about gastrointestinal motility disorders in CCHS patients. This study aims to describe the spectrum of gastrointestinal motility disorders in CCHS and provide PHOX2B genotype-phenotype correlation with Hirschsprung Disease (HD). We reviewed the records of 72 CCHS patients seen at Children's Hospital Los Angeles from 1999 to 2019. Data collected included demographics, PHOX2B genotype, ventilator dependence, medical and surgical history, and gastrointestinal motility studies. Of the 72 patients, 31% had HD, 50% females, and 60% had 20/27 PARM. Rectosigmoid HD formed 73% of the cases whereas long segment (up to splenic flexure involvement) forms represented 23%. Four patients had total colonic aganglionosis, including one patient with 20/25 PARM genotype. One HD patient was identified with colonic myopathy in the residual segment. One patient was found to have achalasia type 1.Conclusion: Nearly one third of our CCHS patients had HD. Although most had 20/27 PARM, 2 patients had 20/25 PARM. Thus, CCHS patients with constipation are at risk for HD regardless of genotype. Colonic myopathy may coexist in treated HD with refractory constipation. Achalasia may occur in patients with CCHS. What is Known: • Patients with CCHS have motility disorders and present with esophageal dysmotility and constipation as a manifestation of their autonomic nervous system dysfunction. • About 20% of patients with CCHS have Hirschsprung disease and previously described to be associated with NPARM and 20/27 PARM genotype. What is New: • Thirty-one percent of CCHS patients in our series have Hirschsprung disease (HD). • HD, including the more severe total colonic aganglionosis was found in a patient with 20/25 PARM genotype suggesting that CCHS patients with constipation should be screened for HD regardless of genotype.
先天性中枢性通气不足综合征（CCHS）是一种自主神经系统功能障碍，由 PHOX2B 基因突变引起。目前对于 CCHS 患者的胃肠道动力障碍知之甚少。本研究旨在描述 CCHS 患者胃肠道动力障碍的范围，并提供与先天性巨结肠（HD）相关的 PHOX2B 基因型-表型相关性。我们回顾了 1999 年至 2019 年期间在洛杉矶儿童医院就诊的 72 例 CCHS 患者的记录。收集的数据包括人口统计学、PHOX2B 基因型、呼吸机依赖、医疗和手术史以及胃肠道动力研究。在 72 例患者中，31%有 HD，50%为女性，60%为 20/27 PARM。直肠乙状结肠 HD 占 73%，长段（直至脾曲受累）占 23%。4 例患者全结肠无神经节细胞，其中 1 例为 20/25 PARM 基因型。1 例 HD 患者在残留段中发现结肠肌病。1 例患者被诊断为 1 型贲门失弛缓症。结论：我们的 CCHS 患者中有近三分之一有 HD。尽管大多数患者为 20/27 PARM，但有 2 例患者为 20/25 PARM。因此，无论基因型如何，有便秘的 CCHS 患者都有发生 HD 的风险。在治疗后仍有难治性便秘的 HD 中可能会并存结肠肌病。在 CCHS 患者中可能会发生贲门失弛缓症。已知：•患有 CCHS 的患者存在运动障碍，并表现为食管动力障碍和便秘，这是其自主神经系统功能障碍的表现。•约 20%的 CCHS 患者患有先天性巨结肠，先前描述与 NPARM 和 20/27 PARM 基因型相关。新发现：•在我们的研究系列中，有 31%的 CCHS 患者患有先天性巨结肠（HD）。•在患有 20/25 PARM 基因型的患者中发现了包括全结肠无神经节细胞在内的更严重的 HD，这表明无论基因型如何，有便秘的 CCHS 患者都应进行 HD 筛查。
