Human genetics and molecular genomics of Chiari malformation type 1.
Trends Mol Med
; 29(12): 1059-1075, 2023 12.
Article
in En
| MEDLINE
| ID: mdl-37802664
Chiari malformation type 1 (CM1) is the most common structural brain disorder involving the craniocervical 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arnold-Chiari Malformation
/
Brain Diseases
Limits:
Humans
Language:
En
Journal:
Trends Mol Med
Journal subject:
BIOLOGIA MOLECULAR
Year:
2023
Document type:
Article
Affiliation country:
Estados Unidos
Country of publication:
Reino Unido