Cystic Fibrosis and Chiari Type I Malformation: Autopsy Study of Two Infants with a Rare Association

Abstract

Cystic fibrosis (CF), an epithelial cell transport disorder caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, is not generally associated with malformations of the central nervous system (CNS). This report describes two African-American children who died at less than 2 years of age with known Chiari I malformations and were found, unexpectedly at autopsy, to have the classic pancreatic and respiratory changes of CF. Both patients had suffered from failure to thrive that had been attributed to their CNS malformations. One child also had recurrent pneumonia and died with Pseudomonas sepsis. Mutational analysis for > 70 common CFTR mutations identified a single delta F508 mutation in one patient and a single 3120+1G to A mutation in the other. Their second CFTR mutations were not identified. The association of CF with Chiari I malformation is not likely to be purely coincidental, as the probability of such an occurrence in African-Americans is greater than one in 7,500,000 patients. It is possible that the CFTR gene may play a previously unrecognized role in CNS development. Alternatively, this CNS abnormality may be acquired due to the metabolic and electrolyte imbalances that characteristically occur in CF.

Rare association between cystic fibrosis, Chiari I malformation, and hydrocephalus in a baby: a case report and review of the literature

“…described two babies with a known diagnosis of Chiari I malformation and hydrocephalus; however, the CF diagnosis was not made until after death [5]. At presentation, the two patients, one boy and one girl, were four months and eight months old, respectively.…”

“…It does not appear that the association is due to a specific type of cystic fibrosis transmembrane conductance regulator (CFTR) mutation as several different point mutations have been described in patients with both conditions [5]. It is possible that the CFTR gene plays an unrecognized role in CNS development.…”

Hypogonadotropic hypogonadism: a consequence of Chiari-I malformation

“…Interestingly, Chiari-I malformation is reported to have a higher prevalence in patients with CF than in the general population [5,6]. The pathophysiological mechanism for this is not well established, however, it is proposed that the CNS abnormality may be acquired due to the characteristic metabolic and electrolyte imbalances associated with CF, or a direct consequence of the mutation in the CF transmembrane conductance regulator gene that may play a previously unrecognised role in CNS development [5].…”