Congenital central hypoventilation syndrome associated with Hirschsprung's Disease: case report and literature review / Síndrome de hipoventilação central congênita associada à doença de Hirschsprung: relato de caso e revisão de literatura

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.

Resumo Objetivo: Relatar caso de neonato com episódios de apneias recorrentes, diagnosticado com síndrome de hipoventilação central congênita (SHCC) associada à doença de Hirschsprung (DH), o que configurou síndrome de Haddad. Descrição do caso: Terceiro filho de casal não consanguíneo, nascido a termo, parto normal sem intercorrências, peso e comprimento adequados para idade gestacional. Logo após o nascimento apresentou bradipneia, bradicardia e cianose, foi submetido à intubação orotraqueal e iniciada antibioticoterapia empírica devido à suspeita de sepse neonatal precoce. Durante internação em UTI neonatal evoluiu com dificuldade de extubação devido a episódios de dessaturação durante sono e vigília. Apresentou quadros recorrentes de hipoglicemia, hiperglicemia, acidose metabólica, distensão abdominal, leucocitose, aumento de proteína C reativa, com hemoculturas negativas e suspeita de erro inato do metabolismo. Aos dois meses foi diagnosticada doença de Hirschsprung de segmento longo, foi submetido à ressecção do segmento e colostomia à Hartmann. Feita pesquisa genética por reação em cadeia da polimerase para pesquisa de SHCC, que evidenciou alelo mutado do gene PHOX2B e confirmou o diagnóstico. Comentários: Trata-se de doença genética rara, de herança autossômica dominante, causada por mutação no gene PHOX2B, localizado na banda cromossômica 4p12, que resulta em disfunção do sistema nervoso autônomo. A SHCC também pode cursar com doença de Hirschsprung e tumores derivados da crista neural. Há correlação entre fenótipo e genótipo, além de grande variabilidade fenotípica intrafamiliar. No período neonatal pode simular quadros de sepse e erros inatos do metabolismo.

Apnea in infants.

OBJECTIVE: The main objective of this study was to describe frequency of risk factors in newborns who present different types of apnea in polysomnographic (PSG) recordings in neonatal care units. METHODS: The study was carried out in neonatal care units of a perinatal tertiary level institution in Mexico City between August 2002 and August 2003. Infants were selected from among 223 infants if they presented any type of apnea event in sleep PSG recordings. RESULTS: Nearly 25% of patients from a neonatal care unit presented apnea events. Infants with apnea showed lower values of age, weight, and cephalic perimeter at birth than infants without apnea, but did not show more neurologic risk factors. Central apnea events were more frequent in infants with preterm birth (birthweight < 1,500 g), obstructive apnea events were observed in infants with hyperbilirubinemia and gastro-esophageal reflux, while mixed events were seen in infants with sepsis, and hyperbilirubinemia. Sleep PSG recordings detected that 36% of infants with apnea have no previous clinic suspicion of the problem. CONCLUSION: Central events of apnea were found more frequent in infants with preterm birth, obstructive events in newborns with hyperbilirubinemia and gastroesophagic reflux, while infants mixed apnea had more frequent hyperbilirubinemia and sepsis.

Accidente cerebrovascular y patologías respiratorias del sueño / Cerebrovascular accident and pathology of sleep

Las patologías respiratorias del sueño tienen una alta prevalencia en pacientes con accidente cerobrovascular (ACV). Varios estudios han sugerido que éstas constituyen un factor de riesgo independiente para los eventos isquémicos cerebrales. Existen mecanismos fisiopatológicos como la hipoxemia, activación simpática, estados de hipercoagubilidad y daño de la pared endotelial que explican la relación existente entre patologías respiratorias del sueño y ACV. Se asocian además a una alta mortalidad y peor pronóstico funcional en pacientes que están cursando con un accidente vascular cerebral en fase aguda. Identificar y tratar estas patologías respiratorias del sueño puede constituirse en una estrategia terapeútica crucial para reducir la morbi-mortalidad asociada al ACV.

Haddad syndrome--congenital central hypoventilation associated with Hirschsprung's disease.

The combination of Congenital Central Hypoventilation with Hirschsprung's disease belongs to the family of diseases now designated as Neurocristopathies. The authors report a polysomnographically documented case and review literature on this disorder.

Hirschsprung's disease associated with Ondine's curse.

This is a case report of a very rare combination of congenital aganglionosis of the intestine (Hirschsprung's disease) and congenital central hypoventilation syndrome-CCHS- (Ondine's curse). The combination is also called Haddad syndrome. In about 50% of the cases of CCHS there is associated Hirschsprung's disease. There are only about 48 cases reported worldwide. The disease has a very high mortality especially in the settings of a developing country.