Registry of Heritable White Matter Disorders in Iran: Clinical, Radiological and Molecular Study of Patients With Classic Leukodystrophies and Genetic Leukoencephalopathies

Background and aim: inherited white matter disorders are a heterogeneous group of neurogenetic disorders affecting mainly the white matter of the central nervous system (cns) with highly variable clinical features. methods: a retrospective cohort study was defined between may 2010 and oct 2019 for myelin disorders clinic registry (mdcr) at children’s medical center hospital, tehran, iran as the main referral children hospital in iran. all patients who were suspected to any types of classic leukodystrophies, genetic leukoencephalopathies (gles) and other rare neurodegenerative disorders with brain white matter involvement who were referred from all provinces around the country or directly presented to our hospital were registered in mdcr. results: all data of 684 patients were recorded in mdcr system through a standard questionnaire designated for mdcr. in 344 patients (50.3%) genetic tests were performed. in 245 out of 344 cases a diagnosis was confirmed by metabolic, radiologic and molecular studies. conclusion: this study is the first report of a large cohort study of classic leukodystrophies and genetic leukoencephalopathies from iran based on an enormous bioregistry system. in concordance with other reports, classic hypomyelinating group was the most common group in our study; however, by advances in next generation sequencing (ngs) method, the number of disorders in hypomyelinating group is increasing. by considering mri and clinical findings, we succeeded to diagnose 34.3% of our patients only by single-gene study method. we used whole exome sequencing (wes) only in less than half of our patients (44.1%). 39.6% of detected variants were novel and classified as class 3 based on acmg classification. a re-classification was observed in a few detected variants during the study from class level of 3 to 1 or 2. there was a diagnostic concordance between mri and clinical findings and genetic diagnosis in more than 80% of patients. these results showed that precise analysis of mri and clinical features along with molecular findings can lead to significant increase of final diagnosis and saving the cost and time. in addition, it could be helpful in providing prenatal diagnosis (pnd) for the affected families who wish to have a healthy child and future studies on gene therapy.