Congenital central hypoventilation syndrome (CCHS) is a rare condition that usually presents soon after birth and is potentially life-shortening if not treated. The defining abnormality is a persistent hypoventilation, most pronounced during sleep, with relative insensitivity to hypercarbia and a lesser insensitivity to hypoxia, beginning in the neonatal period and requiring life-long ventilatory assistance. Changes in the integration of afferent inputs from central and peripheral chemoreceptors in the brainstem are the most likely disease mechanisms.
The association of congenital failure of autonomic control with congenital central hypoventilation syndrome was first reported in 1978. This syndrome is rare; only about 50 cases have been reported worldwide. Congenital failure of autonomic control is a condition caused by congenital absence of ganglion cells from the enteric nervous system, resulting in bowel obstruction ranging in severity from chronic severe constipation to complete obstruction and early neonatal death. It is thought to originate in a failure of migration of neural crest derived precursor cells, although this is controversial and a hostile gut microenvironment may also contribute.
Congenital failure of autonomic control can be caused by mutation in the paired-liked homeobox 2B (PHOX2B) gene as well as in several other genes, including RET, GDNF, EDN3, and BDNF. PHOX2B is the major disease-causing gene, mutated in half to two thirds of patients with congenital failure of autonomic control.
Al Rashdi et al. (2011) and Mahfouz et al. (2011) described a 6-year old Omani girl with congenital central hypoventilation syndrome. She was born to consanguineous parents through normal delivery. Her weight was below average due to dental conditions. She did not have any breathing problems during sleep, and she never complained about headache or visual changes. Her parents confirmed that she had no history of cardiac and pulmonary diseases. After she had a dental extraction surgery with general anesthesia, she suffered from shallow breathing and apnea. The results of the genetic test showed that the patient had a repeat expansion in the polyalanine tract of PHOX2B gene, causing congenital central hypoventilation syndrome. After 65 days in the ICU, she was discharged with portable ventilator for ventilator support during sleep.
Mansoor and Zahrani (2002) analyzed 27 consecutive cases of endoscopic colonic biopsies and surgical colectomy specimens of both male and female cases who were received for investigation of ganglion cells for the Hirschsprung's disease and related disorders. In their study, Mansoor and Zahrani (2002) looked for only three symptoms and all the 27 patients presented with constipation, 15 (55.5%) patients had abdominal distension and no patient presented with diarrhea. Mansoor and Zahrani (2002) suggested that a wider population study for the genetic factors of this frequent congenital disease is highly recommended in the Saudi population.
Trivedi et al. (2011)presented four families with CCHS, three with autosomal dominant inheritance and familial clustering, and one with a de novo mutation resulting in CCHS. Mutations detected in all the families were repeat expansion in the polyalanine tract of PHOX2B gene. Trivedi et al. (2011) demonstrated that phenotypic variability in expression of disease is seen in families with the same mutations in PHOX2B gene. They also commented on the psychosocial costs of the disease and the unrecognized 'morbidity barter' that is part of current management needs to be factored into in all stages of management from childhood to adolescence to adulthood.
While presenting a case study, Al Saadi et al. (2011) linked the presence of congenital central hypoventilation syndrome in a Saudi child to a repeat expansion in the polyalanine tract of PHOX2B gene.
Fogstad and colleges (1989) reported three patients diagnosed with a combination of congenital failure of autonomic control and Hirschsprung's disease. Case one, a male neonate had total colonic aganglionosis, a hypertrophied nerve trunk with increased esterase activity, and apnea requiring endotracheal incubation and ventilation. The baby died aged one month from the combination of enterocolitis, septicaemia and pneumonia. Post-mortem examination revealed patchy bronchopneumonia and generalized cholestasis of the liver. Case two, a female baby, had nocturnal perspiration, sudden awakening with respiratory difficulties and aganglionosis at three months of age, and upper respiratory tract infection followed by apnea lasting 10 to 20 seconds with hypoxia and hypercapnia, seizures, cardiac arrest, and oedema at 20 months of age. Case three, a female baby was diagnosed shortly after birth to have congenital failure of autonomic control and Hirschsprung's disease. The baby had pulmonary complications and total colonic aganglionosis. During infancy she had epileptic seizures and was hypertensive with generalized oedema. In case two and three, at the ages of two and six years, respectively, phrenic nerve stimulators were implanted. Both females remained independent of nocturnal mechanical ventilation two and three years after the commencement of diaphragm pacing. Fogstad and colleges (1989) concluded that patients with congenital failure of autonomic control combined with Hirschsprung's disease, who survive neonatal period should be considered candidates for electrophrenic respiration as an alternative or even treatment of choice for restoring normal breathing and improving the quality of life. [Fodstad H, Ljunggren B, Shawis R. Sleep apnea with intestinal aganglionosis. Report of three cases: therapeutic considerations. Emirates Med J 1989; 7:159-63.]
Al Talabani et al. (1998) studied the pattern of major congenital malformations in 24,233 consecutive live and stillbirth at Corniche hospital, which is the only maternity hospital in Abu Dhabi, between January 1992 and January 1995. A total of 401 babies (16.6/1,000), including 289 Arabs, were seen with major malformation. Sporadic conditions accounted for 26% of the cases. In their study, Al Talabani et al. (1998) observed one case of congenital failure of autonomic control in a family from the United Arab Emirates. Recurrence was not reported in other members of the family. Al Talabani et al. (1998) concluded that their study was very close to representing the true incidence of congenital abnormalities in the whole United Arab Emirates, as they investigated over 98% of deliveries in Abu Dhabi, the capital of United Arab Emirates.
Rahmani et al. (2013) described a female newborn with congenital central hypoventilation syndrome (CCHS). The baby was born via Cesarean section. At birth, she had apneic spells in between breathing and needed initial steps of resuscitation and Naloxone. She was admitted to the NICU due to severe sleep apnea. There was no seizure activity while she was awake. The baby was discharged on long-term ventilator support while asleep.