title: 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.
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, TX 75390-9073, USA.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Rakheja
authors.forename: Yin
authors.initials: Y
authors.lastname: Xu
authors.forename: Dennis K
authors.initials: DK
authors.lastname: Burns
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Veltkamp
authors.forename: Linda R
authors.initials: LR
authors.lastname: Margraf
mesh_terms: D001139:Arnold-Chiari Malformation / Q000150:complications* / Q000235:genetics / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D003550:Cystic Fibrosis / Q000150:complications* / Q000235:genetics / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007223:Infant; D008168:Lung / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D010179:Pancreas / Q000473:pathology
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator