Brain Calcifications: Genetic, Molecular, and Clinical Aspects

Area of Science:

• Neurology
• Genetics
• Pathology

Background:

• Brain calcifications present with diverse neurological symptoms and arise from primary genetic causes or secondary conditions.
• Primary familial brain calcification (PFBC) involves genes like SLC20A2, PDGFB, PDGFRB, XPR1, MYORG, and JAM2.
• Additional genes are linked to complex syndromes featuring brain calcifications and systemic issues, often involving cerebrovascular and blood-brain barrier functions.

Purpose of the Study:

• To provide a comprehensive review of the genetic, molecular, and clinical aspects of brain calcifications.
• To offer a framework for clinicians and researchers studying brain calcification disorders.
• To highlight the growing understanding of pathways involved in brain calcifications as more genes are identified.

Main Methods:

• Comprehensive literature review of genetic, molecular, and clinical studies on brain calcifications.
• Analysis of identified causative genes for primary familial brain calcification.
• Examination of genes associated with complex syndromes involving brain calcifications.

Main Results:

• Identification of key genes (e.g., SLC20A2, PDGFB) associated with primary familial brain calcification.
• Recognition of numerous genes linked to complex syndromes with brain calcifications and other manifestations.
• Highlighting the role of cerebrovascular and blood-brain barrier proteins in brain calcification pathogenesis.

Conclusions:

• The genetic landscape of brain calcifications is expanding, revealing diverse causative factors.
• Understanding the molecular pathways underlying brain calcifications is crucial for clinical management and research.
• This review consolidates current knowledge, providing a valuable resource for the field.