title: Fanconi anemia: correlating central nervous system malformations and genetic complementation groups.
abstract: BACKGROUND
  Congenital central nervous system abnormalities in children with Fanconi anemia are poorly characterized, especially with regard to specific genetic complementation groups.
  
  
  OBJECTIVE
  To characterize the impact of genetic complementation groups on central nervous system anatomy.
  
  
  METHODS
  Through chart review we identified 36 patients with Fanconi anemia with available brain MRIs at the University of Minnesota (average age, 11.3 years; range, 1-43 years; M:F=19:17), which we reviewed and compared to 19 age- and sex-matched controls (average age, 7.9 years; range, 2-18 years; M:F=9:10). Genotypic information was available for 27 patients (15 FA-A, 2 FA-C, 3 FA-G, and 7 FA-D1 [biallelic mutations in BRCA2 gene]).
  
  
  RESULTS
  Of the 36 patients, 61% had at least one congenital central nervous system or skull base abnormality. These included hypoplastic clivus (n=12), hypoplastic adenohypophysis (n=11), platybasia (n=8), pontocerebellar hypoplasia (n=7), isolated pontine hypoplasia (n=4), isolated vermis hypoplasia (n=3), and ectopic neurohypophysis (n=6). Average pituitary volume was significantly less in patients with Fanconi anemia (P<0.0001) than in controls. Basal angle was significantly greater in Fanconi anemia patients (P=0.006), but the basal angle of those with FA-D1 was not significantly different from controls (P=0.239). Clivus length was less in the Fanconi anemia group (P=0.002), but significance was only observed in the FA-D1 subgroup (P<0.0001). Of the seven patients meeting criteria for pontocerebellar hypoplasia, six belonged to the FA-D1 group.
  
  
  CONCLUSIONS
  Patients with Fanconi anemia have higher incidences of ectopic neurohypophysis, adenohypophysis hypoplasia, platybasia and other midline central nervous system skull base posterior fossa abnormalities than age- and sex-matched controls. Patients with posterior fossa abnormalities, including pontocerebellar hypoplasia, are more likely to have biallelic BRCA2 mutations.
authors.affiliation: Department of Radiology, University of Minnesota, MMC 292, 420 Delaware St. SE, Minneapolis, MN, 55455, USA. joh04737@umn.edu.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Johnson-Tesch
authors.affiliation: Department of Radiology, Neuroradiology Section, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Rakhee S
authors.initials: RS
authors.lastname: Gawande
authors.affiliation: Biostatistical Design and Analysis Centre, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Blood and Marrow Transplant Program, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Margaret L
authors.initials: ML
authors.lastname: MacMillan
authors.affiliation: Department of Radiology, Neuroradiology Section, University of Minnesota, Minneapolis, MN, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Nascene
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005199:Fanconi Anemia / Q000150:complications* / Q000235:genetics*; D005260:Female; D024522:Genes, BRCA2; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009154:Mutation; D009421:Nervous System Malformations / Q000000981:diagnostic imaging* / Q000235:genetics*
keywords: BRCA2; Central nervous system; Children; Congenital; Fanconi anemia; Pontocerebellar hypoplasia; Radiology