RES E AR C H Open Access Spinocerebellar ataxia type 29 due to mutations in ITPR1: a case series and review of this emerging congenital ataxia

AbstractBackground: Spinocerebellar ataxia type 29 (SCA29) is an auto somal dominant, non-progressive cerebellar ataxiacharacterized by infantile-onset hypotonia, gross motor delay and cognitive impairment. Affected individuals exhibitcerebellar dysfunction and often have cerebellar atrop hy on neuroimaging. Recently, missense mutations in ITPR1were determined to be responsible.Results: Clinical information on 21 individuals from 15 unrelated families with ITPR1 mutations was retrospectivelycollected using standardized questionnaires, including 11 previously unreported singletons and 2 new patients from apreviously reported family. We describe the genetic, clinical and neuroimaging features of these patients to furthercharacterize the clinical features of this rare condition and assess for any genotype-phenotype correlation for thisdisorder. Our cohort consisted of 9 males and 12 females, with ages ranging from 28 months to 49 years. Diseasecourse was non-progressive with infantile-onset hypotonia and delays in motor and speech development. Gait ataxiawas present in all individuals and 10 (48%) were not ambulating independently between the ages of 3–12 years ofage. Mild-to-moderate cognitive impairment was present in 17 individuals (85%). Cerebellar atrophy developed afterinitial symptom presentation in 13 individuals (72%) and was not associated with disease progression or worseningfunctional impairment. We identified 12 different mutations including 6 novel mutations; 10 mutations were missense(with 4 present in >1 individual), 1 a splice site mutation leading to an in-frame insertion and 1 an in-frame deletion.No specific genotype-phenotype correlations were observed within our cohort.Conclusions: Our findings document significant clinical heterogeneity between individuals with SCA29 in a largecohort of molecularly confirmed cases. Based on the retrospective observed clinical features and disease course, weprovide recommendations for management. Further research into the natural history of SCA29 through prospectivestudies is an important next step in better understanding the condition.■■■■■■■■-7?author_access_token=WxYQd_bkQOgOyup0NYuXwm_BpE1tBhCbnbw3BuzI2RPsYY4dITfgBESAYvQjXGpLqfmo5juFD_o9d7VJLjFVA1vCRMaOIBMUaMoCxmyXMJUG4xp1OoXkVkqgNAYCEJwm30-TQcqA9viugnU7naoEEw%3D%3D