Extended clinical phenotype of late-onset congenital central
hypoventilation syndrome in children with PHOX2B mutations
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.