Abstract
Background: Cerebellar atrophy is a neuroradiological definition that categorizes conditions heterogeneous for clinical findings, disease course, and genetic defect. Most of the papers proposing a diagnostic workup for pediatric ataxias are based on neuroradiology or on the literature and experimental knowledge, with a poor participation of clinics in the process of disease definition. Our study aims to offer a different perspective on the way we approach cerebellar atrophy in developmental age, building a clinical-based diagnostic workup to guide molecular diagnosis. Methods: we recruited 52 patients with pediatric-onset cerebellar atrophy and definite disease categorization. Children underwent brain MRI, neurophysiological exams, metabolic investigations, and muscle biopsy with respiratory chain complex study. Single-gene sequencing, next-generation sequencing NGS panels, whole-exome sequencing (WES), and disease-specific techniques have been used to reach genetic confirmation. Results: Brain MRI is the main method of diagnosis, followed by tests on muscle biopsy and peripheral nervous system study. Other exams (e.g., metabolic investigations or evoked potentials) may be useful to narrow the list of diagnostic possibilities. Conclusions: We propose a diagnostic approach to cerebellar atrophy in children based on clinical findings, and support the evidence that a precise phenotypic definition may lead to the formulation of a definite diagnosis or otherwise guide the back phenotyping process derived from large molecular data.
Highlights
Studies have focused so far on delineating different neuroradiological patterns with Cerebellar Atrophy (CA), while little has been written on the global clinical presentation of the patients
Children who have a CA superimposed to cerebellar hypoplasia had those disorders in which cerebellar degeneration is known to start at a very early stage of development: Pontocerebellar Hypoplasias (PCH) and Congenital Disorders of Glycosylation (CDG) [3,11]
The hypo-atrophic pattern cannot be missed, as its presence consistently narrows the possible diagnosis to a small group of disorders
Summary
Numerous diseases, which especially in children may have a genetic cause, share such a brain-imaging pattern. The diagnostic process is more challenging for cerebellar atrophy, as the radiological patterns are often overlapping, tend to evolve over time, and it is often not possible reach an etiopathological definition based solely on brain Magnetic Resonance Imaging (MRI) findings. Cerebellar atrophy is a neuroradiological definition that categorizes conditions heterogeneous for clinical findings, disease course, and genetic defect. Most of the papers proposing a diagnostic workup for pediatric ataxias are based on neuroradiology or on the literature and experimental knowledge, with a poor participation of clinics in the process of disease definition. Our study aims to offer a different perspective on the way we approach cerebellar atrophy in developmental age, building a clinical-based diagnostic workup to guide molecular diagnosis.
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