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Extended clinical phenotype of late-onset congenital central hypoventilation syndrome in children with PHOX2B mutations
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  • guan yuhong,
  • Xiaohui Wen,
  • Xiaoyan Zhang,
  • Zhifei Xu,
  • Shunying Zhao,
  • haiming yang
guan yuhong
Beijing Children's Hospital Capital Medical University
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Xiaohui Wen
Beijing Children's Hospital Capital Medical University
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Xiaoyan Zhang
Beijing Children's Hospital Capital Medical University
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Zhifei Xu
Beijing Children's Hospital Capital Medical University
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Shunying Zhao
Beijing Children's Hospital Capital Medical University
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haiming yang
Beijing Children's Hospital Capital Medical University

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Abstract

Objective: This study aimed to delineate the clinical and genetic features of late-onset congenital central hypoventilation syndrome (LO-CCHS) in four children. Methods: Clinical data from four children with LO-CCHS, including presentations, genetic testing, and follow-up results, were collected and analyzed at the Department of Respiratory Medicine at Beijing Children’s Hospital, China, from December 2019 to December 2023. Results: Four children (two males, two females) with PHOX2B mutations and LO-CCHS diagnosis were included. Ages of disease onset were 0.75, 4.2, 10.3, and 0.4 years, corresponding diagnostic ages were 6.5, 5.8, 11.3, and 1.6 years, and diagnostic delays ranged from one to five years. All patients exhibited nocturnal bradypnea and hypercapnia. patient 1 presented with pulmonary artery hypertension (PAH) as the initial symptom. Patient 2 experienced recurrent pulmonary hemorrhage (PH) after respiratory infections and genetic testing conformed a CCHS diagnosis. patient 3 exhibited hypersomnia due to increased respiratory resistance triggered by swimming, and patient 4 experienced recurrent cyanosis and lethargy followed by convulsions a year later. Four different PHOX2B mutations were identified: three polyalanine repeat mutations (PARMs) and one non-polyalanine repeat mutation (NPARM). Two of these were de novo mutations and two were respectively inherited from asymptomatic mother. For one to three years follow-up, three of them were in stable condition with oxygen supplement while one (patient 4) dead of respiratory failure. Conclusions: PAH could be as significant phenotypes of LO-CCHS when diagnosis was delayed and PH may be as relevant manifestations of LO-CCHS in children with PHOX2B mutations.