Missing Links Between Genetically Inherited Molecules in Split Cord Malformation and Other Anomaly: A Bench to...

Area of Science:

• Developmental biology
• Genetics
• Neurology

Background:

• Split cord malformation (SCM) is frequently linked to vertebral fusions, known as Klippel-Feil anomaly.
• Embryological theories and recent research suggest a complex genetic basis for SCM and associated conditions.

Purpose of the Study:

• To investigate the etiopathogenesis of split cord malformation (SCM) and its associated vertebral fusions.
• To document the origin of split cord and the involvement of a spectrum of genes in SCM.
• To provide an updated overview of SCM, integrating experimental and human subject data.

Main Methods:

• Literature review using PubMed/MEDLINE, Cochrane Review, Hinari, and Google Scholar.
• Analysis of relative risk and molecular mechanisms of major genes and variants.
• Discussion of Mendelian and Non-Mendelian genetic components in SCM.

Main Results:

• A midline lesion bisecting the neuroepithelium and notochordal plate can cause complete cervical cord splitting with anterior bony defects.
• Localized disturbances in cervical neural tube closure lead to SCM with partial dorsal cord splitting and posterior vertebral defects.
• SCM is associated with other diseases, indicating a complex interplay of genetic factors.

Conclusions:

• This study presents a broad spectrum of variants contributing to SCM, from experimental models to human subjects.
• Complex interactions of mutant variants and potential second-hit alterations are implicated in SCM development.
• This bench-to-bedside approach provides comprehensive information to address the global burden of SCM and associated diseases.