X-Linked Epilepsies: A Narrative Review

Area of Science:

• Neurogenetics
• Epileptology
• Genomic Medicine

Background:

• X-linked epilepsies are a complex group of genetic disorders frequently co-occurring with intellectual disability.
• Numerous X-linked genes have been identified, causing epilepsy syndromes and developmental and epileptic encephalopathies (DEEs).
• Phenotypic characterization varies, with some genes well-defined and others recently discovered.

Purpose of the Study:

• To provide a comprehensive and updated narrative review of X-linked epilepsies.
• To consolidate information on well-characterized and newly identified X-linked epilepsy genes.
• To assist clinicians in the genetic diagnosis and management of patients with X-linked epilepsy.

Main Methods:

• Comprehensive literature review of X-linked epilepsy syndromes.
• Analysis of electro-clinical phenotypes associated with identified genes.
• Discussion of inheritance patterns and complicating factors like X-chromosome inactivation.

Main Results:

• Detailed description of established X-linked epileptic syndromes (e.g., PCDH19, CDKL5, MECP2 related DEEs).
• Overview of epilepsies linked to X-linked neuronal migration disorders (e.g., ARX, DCX, FLNA).
• Summary of DEEs associated with recently identified genes (e.g., SLC9A6, SYN1, PIGA).

Conclusions:

• X-linked epilepsies present a heterogeneous spectrum of conditions.
• Identifying an X-linked inheritance pattern can be challenging due to complex inheritance and modifying factors.
• This review serves as a valuable resource for understanding and managing X-linked epilepsies.