Stavros M Stivaros1,2,3, Robert Alston4, Neville B Wright2, Kate Chandler5, Denise Bonney6,7, Robert F Wynn7,8, Andrew M Will6, Maqsood Punekar9, Sean Loughran10, John-Paul Kilday3,7, Detlev Schindler11, Leena Patel12, Stefan Meyer3,7,13. 1. 1 Centre for Imaging Sciences, University of Manchester, Institute of Population Health, Manchester, UK. 2. 2 Academic Unit of Paediatric Radiology, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. 3. 3 Children's Brain Tumour Research Network, University of Manchester, Royal Manchester Children's Hospital, Manchester, UK. 4. 4 National Drug Evidence Centre (NDEC), Centre for Epidemiology, Institute of Population Health, University of Manchester, Manchester, UK. 5. 5 Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Saint Mary's Hospital, Manchester, UK. 6. 6 Department of Paediatric Haematology, Royal Manchester Children's Hospital, Manchester, UK. 7. 7 Department of Paediatric Oncology and Haematology, Royal Manchester children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Health Science Centre, Manchester, UK. 8. 8 Blood and Marrow Transplant Unit, Royal Manchester Children's Hospital, Manchester, UK. 9. 9 Department of Haematology, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK. 10. 10 Academic Department of Otolaryngology and Head and Neck Surgery, Manchester Royal Infirmary, Manchester, UK. 11. 11 University of Wuerzburg, Department of Human Genetics, Biozentrum, Am Hubland, Wuerzburg, Germany. 12. 12 University of Manchester and Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, UK. 13. 13 Academic Unit of Paediatric and Adolescent Oncology, University of Manchester, c/o Young Oncology Unit, The Christie NHS Foundation Trust, Manchester, UK.
Abstract
OBJECTIVE: Fanconi anaemia (FA) is an inherited disease associated with congenital and developmental abnormalities resulting from the disruption of a multigenic DNA damage response pathway. This study aimed to define the MRI appearances of the brain in patients with FA in correlation with their genetic and clinical features. METHODS: A review of the brain MRI in 20 patients with FA was performed. Pituitary size and frequencies of the radiological findings of individuals with FA and age-matched controls were determined. RESULTS: Abnormalities were identified in 18 (90%) patients with FA, the commonest being a small pituitary (68%, p < 0.01 females and p < 0.001 males). In five cases (25%, p = 0.02), the pituitary morphology was also abnormal. Posterior fossa abnormalities were seen in six cases (30%, p = 0.01) including Chiari I malformation (n = 3), Dandy-Walker variant (n = 2) and cerebellar atrophy (n = 2). Six patients (30%, p = 0.01) had morphological structural variation of the corpus callosum (CC). CONCLUSION: The incidence of central nervous system (CNS) abnormalities in FA is higher than previously reported, with a midline predominance that points to impact in the early stages of CNS development. MRI brain imaging is important for endocrine assessment and pre-transplant evaluation and can make an important contribution to clinical decision-making. ADVANCES IN KNOWLEDGE: The incidence of brain structural abnormalities in FA is higher than previously reported, with abnormalities of the posterior fossa, CC and pituitary being common. There is an association with gender and reduction in pituitary size which does not strongly correlate with biochemically evident endocrine abnormality.
OBJECTIVE: Fanconi anaemia (FA) is an inherited disease associated with congenital and developmental abnormalities resulting from the disruption of a multigenic DNA damage response pathway. This study aimed to define the MRI appearances of the brain in patients with FA in correlation with their genetic and clinical features. METHODS: A review of the brain MRI in 20 patients with FA was performed. Pituitary size and frequencies of the radiological findings of individuals with FA and age-matched controls were determined. RESULTS: Abnormalities were identified in 18 (90%) patients with FA, the commonest being a small pituitary (68%, p < 0.01 females and p < 0.001 males). In five cases (25%, p = 0.02), the pituitary morphology was also abnormal. Posterior fossa abnormalities were seen in six cases (30%, p = 0.01) including Chiari I malformation (n = 3), Dandy-Walker variant (n = 2) and cerebellar atrophy (n = 2). Six patients (30%, p = 0.01) had morphological structural variation of the corpus callosum (CC). CONCLUSION: The incidence of central nervous system (CNS) abnormalities in FA is higher than previously reported, with a midline predominance that points to impact in the early stages of CNS development. MRI brain imaging is important for endocrine assessment and pre-transplant evaluation and can make an important contribution to clinical decision-making. ADVANCES IN KNOWLEDGE: The incidence of brain structural abnormalities in FA is higher than previously reported, with abnormalities of the posterior fossa, CC and pituitary being common. There is an association with gender and reduction in pituitary size which does not strongly correlate with biochemically evident endocrine abnormality.
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