Inherited white matter disorders in children

Abstract

Inherited white matter disorders (IWMDs), otherwise known as leukodystrophies, represent a group of rare and heterogenous neurological conditions affecting the white matter of the central nervous system (CNS). With a wide range of differential diagnoses and associated medical complexities, they often pose a diagnostic challenge to clinicians. Rapid technological advancement including the availability of genetic investigations such as whole genome sequencing (WGS) is leading to an increasing number of patients with a confirmed genetic diagnosis. For the majority of IWMDs there is no specific treatment, and the focus of clinical management remains symptomatic and involves a multidisciplinary team and holistic approaches. Up until recently, only natural history trials were available, but now the focus is shifting to novel targeted therapies. Early diagnosis and prompt referral to specialized IWMD centers is crucial for optimum management of affected children or asymptomatic affected siblings. Collaborative efforts are needed to achieve two important goals 1) to establish international patient registries for long term natural history and recruitment to new treatment trials and 2) to encourage wider newborn screening programmes for early detection of these rare diseases at the asymptomatic stage. In this review, we aim to summarise the common clinical presentations, diagnostic investigations, management and prognosis of the more commonly encountered inherited white matter disorders in children.