Congenital central hypoventilation syndrome associated with Hirschsprung's Disease: case report and literature review

Abstract

Objective:To report the case of a newborn with recurrent episodes of apnea, diagnosed with Congenital Central hypoventilation syndrome (CCHS) associated with Hirschsprung's disease (HD), configuring Haddad syndrome.Case description:Third child born at full-term to a non-consanguineous couple through normal delivery without complications, with appropriate weight and length for gestational age. Soon after birth he started to show bradypnea, bradycardia and cyanosis, being submitted to tracheal intubation and started empiric antibiotic therapy for suspected early neonatal sepsis. During hospitalization in the NICU, he showed difficulty to undergo extubation due to episodes of desaturation during sleep and wakefulness. He had recurrent episodes of hypoglycemia, hyperglycemia, metabolic acidosis, abdominal distension, leukocytosis, increase in C-reactive protein levels, with negative blood cultures and suspected inborn error of metabolism. At 2 months of age he was diagnosed with long-segment Hirschsprung's disease and was submitted to segment resection and colostomy through Hartmann's procedure. A genetic research was performed by polymerase chain reaction for CCHS screening, which showed the mutated allele of PHOX2B gene, confirming the diagnosis.Comments:This is a rare genetic, autosomal dominant disease, caused by mutation in PHOX2B gene, located in chromosome band 4p12, which results in autonomic nervous system dysfunction. CCHS can also occur with Hirschsprung's disease and tumors derived from the neural crest. There is a correlation between phenotype and genotype, as well as high intrafamilial phenotypic variability. In the neonatal period it can simulate cases of sepsis and inborn errors of metabolism.

Central Congenital Hypoventilation Syndrome associated with hypoglycemia and seizure

“…Hirschsprungs is commonly seen in association with CCHS when there is a non-polyalynine expansion mutation. Among those patients with the most common mutation, polyalanine expansion of 20/27, only 20% have associated Hirschsprungs disease [7]. While in the previously presented case reports none of the patients were reported to have Hirschsprungs, an additional case report of a 39 week infant with both CCHS and Hirschsprungs, associated hypoglycemia was found [7].…”

“…Among those patients with the most common mutation, polyalanine expansion of 20/27, only 20% have associated Hirschsprungs disease [7]. While in the previously presented case reports none of the patients were reported to have Hirschsprungs, an additional case report of a 39 week infant with both CCHS and Hirschsprungs, associated hypoglycemia was found [7]. No clear association of stand-alone Hirschsprungs with recurrent hypoglycemia appears to exist and this may prove be an area to further investigate.…”

Congenital Central Hypoventilation Syndrome in Neonates: Report of Fourteen New Cases and A Review of the Literature

“…Our initial search identified 53 neonatal-onset CCHS cases from 33 papers [10, [42][43][44]. After systematically reviewing, seven cases were excluded from our analyses because of lacking important information or co-occurrence of other genetic conditions.…”

Neurocristopathies: Enigmatic Appearances of Neural Crest Cell–derived Abnormalities

“…In Waardenburg syndrome type IV, mutations of the SOX10 gene have been known to cause Hirschsprung disease owing to the inability of defective vagal NCCs to form the enteric neural plexus within the bowel (43). Hirschsprung disease is seen in up to 20% of persons with congenital central hypoventilation syndrome, in whom mutations in the PHOX2B gene have been implicated (44).…”