Fanconi anemia: correlating central nervous system malformations and genetic complementation groups

Pediatr Radiol. 2017 Jun;47(7):868-876. doi: 10.1007/s00247-017-3817-x. Epub 2017 Mar 10.

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.

Materials and 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.

Conclusion: 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.

Keywords: BRCA2; Central nervous system; Children; Congenital; Fanconi anemia; Pontocerebellar hypoplasia; Radiology.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Fanconi Anemia / complications*
  • Fanconi Anemia / genetics*
  • Female
  • Genes, BRCA2*
  • Humans
  • Infant
  • Magnetic Resonance Imaging / methods*
  • Male
  • Mutation
  • Nervous System Malformations / diagnostic imaging*
  • Nervous System Malformations / genetics*