Congenital Central Hypoventilation Syndrome
Discussion
CCHS has an incidence of approximately 1/150,000 to 1/200,000 live
births. Diagnosis was traditionally made in the neonatal period
presenting with hypoventilation and hypercarbia requiring mechanical
ventilation. However, due to variable penetrance there has been
increased diagnosis in early childhood to adulthood. The PSG image
demonstrates several features consistent with CCHS, including
hypoventilation (elevated CO2 values), frequent central apneas, and
hypoxemia. Also note that respiratory events and hypoventilation were
more frequent during NREM, which is typical of CCHS.
Late onset CCHS should be suspected in infants and children with
failure to extubate, apnea/hypoventilation from minimal sedation,
unresolved central sleep apnea, or difficulty weaning from respiratory
support after respiratory illness. These signs should prompt genetic
evaluation of the disease defining PHOX2B gene. This patient had PHOX2B
gene testing, which was positive for a non-polyalanine repeat genetic
mutation (N-PARM), specifically p.R141Q. Hirschsprung disease, autonomic
abnormalities, ophthalmic abnormalities, neural crest tumors and
cognitive deficits may all accompany CCHS.
The majority (greater than 90%) of CCHS patients demonstrate an
in-frame PARM mutation with 4 to 13 additional alanines. In addition,
there are over 100 NPARM mutations due to frameshift, missense, nonsense
and stop codon mutations. NPARM mutations are typically associated with
the most severe disease phenotypes.
Children under 3 years of age with CCHS require frequent
comprehensive physiologic testing every 6 months, including:
polysomnography, echocardiogram, CBC/bicarb/reticulocytes, 72-hour EKG,
neurocognitive testing, and neural crest tumor surveillance (depending
on genotype). Respiratory support may be accomplished either via
tracheostomy or non-invasive ventilation. This patient had a
tracheostomy and gastrostomy tube placed for management of his CCHS.
Adequate ventilatory support helps prevent development of cor-pulmonale
and intellectual disability from impaired gas exchange.
References
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Healy, F. and C.L. Marcus, Congenital central hypoventilation syndrome in children. Paediatr Respir Rev, 2011. 12(4): p. 253-63.
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Weese-Mayer, D.E., et al., Congenital central hypoventilation
syndrome: a bedside-to-bench success story for advancing early diagnosis
and treatment and improved survival and quality of life. Pediatr Res,
2017. 81(1-2): p. 192-201.
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Weese-Mayer, D.E., et al., An official ATS clinical policy statement:
Congenital central hypoventilation syndrome: genetic basis, diagnosis,
and management. Am J Respir Crit Care Med, 2010. 181(6): p. 626-44.