Human genetics and molecular genomics of Chiari malformation type 1.

Trends in molecular medicine
Authors
Keywords
Abstract

Chiari malformation type 1 (CM1) is the most common structural brain disorder involving the pboard1 junction, characterized by caudal displacement of the cerebellar tonsils below the foramen magnum into the spinal canal. Despite the heterogeneity of CM1, its poorly understood patho-etiology has led to a 'one-size-fits-all' surgical approach, with predictably high rates of morbidity and treatment failure. In this review we present multiplex CM1 families, associated Mendelian syndromes, and candidate genes from recent whole exome sequencing (WES) and other genetic studies that suggest a significant genetic contribution from inherited and de novo germline variants impacting transcription regulation, craniovertebral osteogenesis, and embryonic developmental signaling. We suggest that more extensive WES may identify clinically relevant, genetically defined CM1 subtypes distinguished by unique neuroradiographic and neurophysiological endophenotypes.

Year of Publication
2023
Journal
Trends in molecular medicine
Date Published
10/2023
ISSN
1471-499X
DOI
10.1016/j.molmed.2023.08.013
PubMed ID
37802664
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