Neonatal Congenital Central Hypoventilation Syndrome: Why We Should not Sleep on it. Literature Review of Forty-two Neonatal Onset Cases

Abstract

: Congenital Central Hypoventilation Syndrome (CCHS), also referred with the expression “Ondine’s Curse”, is a rare genetic life-long disease resulting from the mutation of PHOX2B gene on chromosome 4p12.3. CCHS represents an autonomic nervous system disorder; its more fearsome manifestation is central hypoventilation, due to a deficient response of chemoreceptors to hypercapnia and hypoxia. Several associated symptoms can occur, such as pupillary anomalies, arrhythmias, reduced heart rate variability, esophageal dysmotility, and structural comorbidities (Hirschsprung’s Disease or neural crest tumours). : CCHS typical onset is during the neonatal period, but cases of delayed diagnosis have been reported; moreover, both sporadic or familial cases can occur. : In preterm newborns, asphyxia and typical prematurity-related findings may overlap CCHS clinical manifestations and make it harder to formulate a correct diagnosis. : The early recognition of CCHS allows appropriate management, useful to reduce immediate and long- term consequences.

Obstructive Apneas in a Mouse Model of Congenital Central Hypoventilation Syndrome

“…( A ) Schematic representations of an isolated brainstem preparation (left), a coronal brainstem slice (right, top) and a sagittal brainstem slice (right, bottom) with the corresponding position of the retrotrapezoid nucleus (RTN; red shading), the preBötzinger complex (preBötC; orange shading) and the hypoglossal (XII) nucleus (gray shading). The double-headed violet arrows indicate the coronal (1) and sagittal (2) plans of section. The violet rectangles delimit the areas shown in B.…”

Apnea In A Term Neonate: Expanding The Differential Diagnosis

“…Individuals with CCHS present with hypoventilation, shallow breathing, and decreased respiratory rates, especially during non-REM sleep [3,6]. Central apnea and cyanosis often result in the need for mechanical ventilation shortly after birth.…”

“…Tumors of neural crest origin can also occur, also more common in patients with NPARMs [3]. Patients with CCHS frequently have autonomic nervous system dysfunction, including pupillary anomalies, blood pressure changes, temperature instability, and esophageal dysmotility as well as cardiac arrhythmias and prolonged sinus pauses [6]. Almost all individuals affected with CCHS require tracheostomy with long-term positive-pressure ventilation [3,7].…”

Adolescent Congenital Central Hypoventilation Syndrome: An Easily Overlooked Diagnosis

“…PARMs are located in the second polyalanine repeat sequence in exon 3 of PHOX2B, and they are more prevalent than NPARMs [1]. Up to 50% of patients with CCHS also present with Hirschsprung's disease (Haddad syndrome) [2]. CCHS is characterized by a lack of respiratory drive, manifesting primarily during non-rapid eye movement (NREM) sleep.…”