Abstract：
Congenital central hypoventilation syndrome (CCHS) is a rare condition characterized by central hypoventilation, leading to the majority of patients being dependent on ventilatory support during sleep. This condition is often accompanied by various associated symptoms, due to a PHOX2B gene variant involved in neuronal crest cell migration. This study is the first to review the characteristics and outcomes in children with CCHS on long-term mechanical ventilation in the Netherlands. We performed a retrospective study of all CCHS patients treated in the 4 Centers of Home Mechanical Ventilation of the University Medical Centers in the Netherlands from 2000 till 2022 by collecting information from the electronic medical records, documented during follow-up. We included 31 patients, out of which 27 exhibited a known genetic profile associated with CCHS, while no PHOX2B variant was identified in the remaining patients. Among the 27 patients with known genetic profiles, 10 patients had a non-polyalanine repeat expansion mutation (NPARM), followed by 20/27, 20/25, and 20/26 polyalanine repeat expansion mutations (PARMs) in descending order. The most common presentation involved respiratory failure or apneas during the neonatal period with an inability to wean off ventilation. The majority of patients required ventilatory support during sleep, with four patients experiencing life-threatening events related to this dependency. Daily use of ventilatory support varied among different genetic profiles. All genotypes reported comorbidities, with Hirschsprung\'s disease and cardiac arrhythmias being the most reported comorbidities. Notably, Hirschprung\'s disease was exclusively observed in patients with a 20/27 PHOX2B variant.
CONCLUSIONS: Our study results suggest that in our cohort, the genotype is not easily associated to the phenotype in CCHS. Consistent with these findings and international literature, we recommend a thorough annual evaluation for all patients with CCHS to ensure optimal management and follow-up.
BACKGROUND: • The majority of CCHS patients are dependent on ventilatory support. • Variants in the PHOX2B gene are responsible for the characteristics of CCHS.
BACKGROUND: • This study provides insight into the clinical course and long-term outcomes of CCHS patients in the Netherlands. • In CCHS, the genotype is not easily associated with the phenotype, requiring a thorough life-long follow-up for all patients.
CONCLUSIONS: Our study results suggest that in our cohort, the genotype is not easily associated to the phenotype in CCHS. Consistent with these findings and international literature, we recommend a thorough annual evaluation for all patients with CCHS to ensure optimal management and follow-up.
BACKGROUND: • The majority of CCHS patients are dependent on ventilatory support. • Variants in the PHOX2B gene are responsible for the characteristics of CCHS.
BACKGROUND: • This study provides insight into the clinical course and long-term outcomes of CCHS patients in the Netherlands. • In CCHS, the genotype is not easily associated with the phenotype, requiring a thorough life-long follow-up for all patients.
摘要：
先天性中枢通气不足综合征（CCHS）是一种罕见的以中枢通气不足为特征的疾病，导致大多数患者在睡眠期间依赖通气支持。这种情况通常伴有各种相关症状，由于PHOX2B基因变异参与神经元c细胞迁移。这项研究首次回顾了荷兰长期机械通气的CCHS儿童的特征和结果。从2000年到2022年，我们通过从电子病历中收集信息，对在荷兰大学医学中心的4个家庭机械通气中心治疗的所有CCHS患者进行了回顾性研究。在随访期间记录。我们纳入了31名患者，其中27个表现出与CCHS相关的已知遗传特征，而其余患者未发现PHOX2B变异。在已知遗传特征的27名患者中，10例患者具有非聚丙氨酸重复扩增突变（NPRM），然后是20/27、20/25和20/26多丙氨酸重复扩增突变(PARM)。最常见的表现包括新生儿期间的呼吸衰竭或呼吸暂停，无法戒断通气。大多数患者在睡眠期间需要通气支持，有四名患者经历了与这种依赖相关的危及生命的事件。通气支持的日常使用因遗传特征而异。所有基因型都报告了合并症，Hirschsprung病和心律失常是报告最多的合并症。值得注意的是,仅在具有20/27PHOX2B变体的患者中观察到Hirschprung病。
结论：我们的研究结果表明，在我们的队列中，基因型不容易与CCHS的表型相关。与这些发现和国际文献一致，我们建议对所有CCHS患者进行全面的年度评估,以确保最佳管理和随访.
背景：•大多数CCHS患者依赖于通气支持。•PHOX2B基因中的变体负责CCHS的特征。
背景：•本研究深入了解荷兰CCHS患者的临床病程和长期预后。•在CCHS中，基因型不容易与表型相关联，需要对所有患者进行彻底的终身随访。
结论：我们的研究结果表明，在我们的队列中，基因型不容易与CCHS的表型相关。与这些发现和国际文献一致，我们建议对所有CCHS患者进行全面的年度评估,以确保最佳管理和随访.
背景：•大多数CCHS患者依赖于通气支持。•PHOX2B基因中的变体负责CCHS的特征。
背景：•本研究深入了解荷兰CCHS患者的临床病程和长期预后。•在CCHS中，基因型不容易与表型相关联，需要对所有患者进行彻底的终身随访。
