Mother–Daughter Transmission of Congenital Central Hypoventilation Syndrome

Abstract

The cause of congenital central hypoventilation syndrome (CCHS) is unknown, but a genetic etiology is strongly suspected. We report a 25-year-old woman with CCHS (no Hirschsprung's disease) who gave birth to a daughter who also has CCHS. This suggests a dominant mode of inheritance for CCHS in this family. Pregnancy can be associated with physiologic challenges in CCHS. The increase in endogenous progesterone may stimulate breathing and may possibly improve symptoms of hypoventilation. Although this patient did not have any worsening in symptoms, her hyperoxic hypercapnic rebreathing ventilatory response was not different when pregnant versus when not pregnant. Ventilatory support for the patient was successfully managed with diaphragm pacing throughout the pregnancy without the need to adjust settings, despite the enlarged abdomen during pregnancy. We conclude that CCHS may be an inherited disorder. Increased endogenous progesterone during pregnancy has no effect on the ventilatory response, and diaphragm pacing can successfully provide adequate ventilation throughout pregnancy.

Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome

“…A genetic origin of CCHS 1 has long been suspected based on concordance in monozygotic twins 2 , rare familial cases (siblings, half-siblings, and mother-tochild transmission) 3 and segregation analysis suggesting an autosmal dominant locus with low penetrance or a multigenic model 4 . So far, only lowpenetrant predisposing mutations of the RET-Glial cell line-derived neurotrophic factor (GDNF), endothelin 3 (EDN3) and brain-derived neurotrophic factor (BDNF) pathways have been reported in a few individuals with CCHS [5][6][7] .…”

Late-onset central hypoventilation syndrome: a family genetic study

“…The syndrome is usually idiopathic but may occur in association with Hirschprung's disease and disorders of neural crest origin. Studies in monozygotic twins, female siblings, male and female half-siblings, and mother-child transmission support a genetic aetiology [2][3][4][5][6]. More recently, an autosomal dominant mode of inheritance has been proposed following the finding of high-frequency (91-97%) heterozygous expansion mutations in a polyalanine tract within exon 3 of PHOX2B gene [7,8].…”

Case report of Haddad syndrome in a newborn: congenital central hypoventilation syndrome and Hirschsprung's disease

“…Prenatal testing for pregnancies at risk is possible if the expansion mutation has been identified in an affected family member. 6,9 Hypoventilation in CCHS is the result of depressed or absent ventilatory sensitivity and arousal response to hypercarbia and hypoxemia or combination of both. Perception of asphyxia is absent; so affected children do not develop dyspnea in response to increased oxygen demand while exercising or in case of respiratory infection.…”