title: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hospital de Base do Distrito Federal (HBDF), Brasília, DF, Brasil; Universidade de Brasília (UnB), Brasília, DF, Brasil. Electronic address: rsandoval.med@gmail.com.
authors.forename: Renata Lazari
authors.initials: RL
authors.lastname: Sandoval
authors.affiliation: Universidade de Brasília (UnB), Brasília, DF, Brasil; Hospital Materno Infantil de Brasília (HMIB), Brasília, DF, Brasil.
authors.forename: Carlos Moreno
authors.initials: CM
authors.lastname: Zaconeta
authors.affiliation: Faculdade de Medicina, Universidade Católica de Brasília (UCB), Brasília, DF, Brasil.
authors.forename: Paulo Roberto
authors.initials: PR
authors.lastname: Margotto
authors.affiliation: Universidade de Brasília (UnB), Brasília, DF, Brasil; Secretaria de Estado de Saúde do Distrito Federal, Brasília, DF, Brasil.
authors.forename: Maria Teresinha de Oliveira
authors.initials: MT
authors.lastname: Cardoso
authors.affiliation: Hospital Materno Infantil de Brasília (HMIB), Brasília, DF, Brasil; Secretaria de Estado de Saúde do Distrito Federal, Brasília, DF, Brasil.
authors.forename: Evely Mirella Santos
authors.initials: EM
authors.lastname: França
authors.affiliation: Secretaria de Estado de Saúde do Distrito Federal, Brasília, DF, Brasil.
authors.forename: Cristina Touguinha Neves
authors.initials: CT
authors.lastname: Medina
authors.affiliation: Secretaria de Estado de Saúde do Distrito Federal, Brasília, DF, Brasil.
authors.forename: Talyta Matos
authors.initials: TM
authors.lastname: Canó
authors.affiliation: Hospital de Base do Distrito Federal (HBDF), Brasília, DF, Brasil.
authors.forename: Aline Saliba de
authors.initials: AS
authors.lastname: Faria
mesh_terms: D006627:Hirschsprung Disease; D006801:Humans; D007040:Hypoventilation / Q000150:complications / Q000151:congenital*; D007231:Infant, Newborn; D008297:Male; D020182:Sleep Apnea, Central / Q000150:complications*
keywords: Congenital central hypoventilation syndrome; Doença de Hirschsprung; Gene PHOX2B; Haddad syndrome; Hirschsprung's disease; Ondine syndrome; PHOX2B gene; Síndrome de Haddad; Síndrome de Ondine; Síndrome de hipoventilação central congênita
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