The genetics of congenital central hypoventilation syndrome: clinical implications

Abstract

John Bishara,1 Thomas G Keens,1,2 Iris A Perez1,2 1Division of Pediatric Pulmonology and Sleep Medicine, Children’s Hospital Los Angeles, Los Angeles, CA, USA; 2Department of Pediatrics, Keck School of Medicine of USC, Los Angeles, CA, USA Abstract: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder of the autonomic nervous system (ANS) and respiratory control. This disorder, formerly referred to as Ondine’s curse, is due to a mutation in the PHOX2B gene that affects the development of the neural crest cells. CCHS has an autosomal dominant pattern of inheritance. Majority of the patients have a polyalanine repeat mutation (PARM) of the PHOX2B, while a small group has non-PARM (NPARM). Knowledge of the patient’s PHOX2B gene mutation helps predict a patient’s clinical presentation and outcome and aids in anticipatory management of the respiratory and ANS dysfunction. Keywords: diaphragm pacing, noninvasive positive pressure ventilation, genetic counseling, genetic testing, CCHS, PHOX2B, congenital central hypoventilation syndrome

Keywords

• Congenital central hypoventilation syndrome
• PHOX2B
• polyalanine repeat mutation
• PARM
• NPARM