Natural history of Alexander disease: A multicentric survey of 75 patients (reporting clinical, radiological and genetic characteristics in).
(2017) European Paediatric Neurology Society — Location: Lyon, France (20.June.2017)
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- Abstract
- Alexander disease (AxD) is rare neurodegenerative disease caused by dominant mutations in the glial fibrillary acidic protein (GFAP). Based on clinical and radiological characteristics, patients have been historically classified in three age-dependent sub- types: Infantile forms (>2 years), juvenile forms (2e13 years) and adult forms. Recently, a new classification has been proposed, dividing patients in type I and type II according to the age at onset (before versus after 4 years). We report retrospectively on 75 patients, 66 children and 9 adults, all diagnosed in France and mostly still followed in European neuropediatric centers. We were interested in age at onset, presence of psychomotor delay before appearance of neurologic symptoms, types of clinical signs, acute episodes of aggravation, neurological deterioration, age of death. We analysed all available brain MRI for each patient and attempted to establish a phenotype-genotype correlation. 49 (65%) patients began before 2 years old, 10 (13%) between 2 and 13, 6 (8%) after 13. First signs were developmental delay (71%) and regression (20%) before 2 years old, anorexia, vomiting, bulbar signs (41%) between 2 and 13, motor disabilities (100%) after 13. The evolution was characterised by occurrence of motor symp- toms in all patients (100%), epilepsy in 42 (56%), regression in 39 (52%), and macrocephaly in 25 patients (33%). Natural history of some patients was also marked by recurrent acute episodes of vomiting, comas, for which different pathological hypothesis are discussed based on MRI analysis. 16 patients (20%) died, mostly between 2 and 13 years (11), three during the first year of life. R239 mutations seem to be responsible for severest pre- sentations. Our data precise the natural history of AxD in a cohort of 75 patients, highlight some neuroradiological particu- larities and support a real phenotype-genotype correlation.
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Renaldo, F., Mignot, C., Tonduti, D., Doummmar, D., Bertini, E., Paquay, S., Abuawad, M., Dorboz, I., Samaan, S., El Maleh, M., Chalard, F., Boespflug-Tanguy, O., Burglen, L., & Rodriguez, D. (2017). Natural history of Alexander disease: A multicentric survey of 75 patients (reporting clinical, radiological and genetic characteristics in). European Journal of Paediatric Neurology, 21, 162. https://hdl.handle.net/2078.5/67475 (Original work published 2017)