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

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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.

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Authors and Affiliations

  1. Department of Radiology, University of Minnesota, MMC 292, 420 Delaware St. SE, Minneapolis, MN, 55455, USA

    Benjamin A. Johnson-Tesch

  2. Department of Radiology, Neuroradiology Section, University of Minnesota, Minneapolis, MN, USA

    Rakhee S. Gawande & David R. Nascene

  3. Biostatistical Design and Analysis Centre, University of Minnesota, Minneapolis, MN, USA

    Lei Zhang

  4. Blood and Marrow Transplant Program, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    Margaret L. MacMillan

Authors
  1. Benjamin A. Johnson-Tesch
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  2. Rakhee S. Gawande
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  3. Lei Zhang
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  4. Margaret L. MacMillan
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  5. David R. Nascene
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Correspondence to Benjamin A. Johnson-Tesch.

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Johnson-Tesch, B.A., Gawande, R.S., Zhang, L. et al. Fanconi anemia: correlating central nervous system malformations and genetic complementation groups. Pediatr Radiol 47, 868–876 (2017). https://doi.org/10.1007/s00247-017-3817-x

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  • DOI: https://doi.org/10.1007/s00247-017-3817-x

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