New Evidence Suggests a Much Complex Classification for the Genetic Pattern of Inheritance in Primary Brain...

Area of Science:

• Neurology
• Genetics
• Neuroscience

Background:

• Primary familial brain calcification (PFBC), or Fahr's disease, is characterized by calcium phosphate deposition in brain regions like the basal ganglia.
• PFBC typically presents with neurological and psychiatric symptoms in adulthood and is linked to autosomal dominant gene variants (e.g., SLC20A2, XPR1).

Purpose of the Study:

• To discuss recent case reports that challenge established genetic associations and inheritance patterns in PFBC.
• To explore the implications of rare homozygous gene variants in PFBC, particularly concerning early-onset disease phenotypes.

Main Methods:

• Review of recent case studies (Ceylan et al., 2022; Al-Kasbi et al., 2022) focusing on genetic variants and clinical presentations.
• Analysis of inheritance patterns, including heterozygous and homozygous mutations in genes like SLC20A2 and XPR1.

Main Results:

• A novel biallelic variant in SLC20A2 was reported, associated with severe, early-onset PFBC mimicking pseudo-TORCH syndrome.
• Biallelic XPR1 gene manifestation was linked to early PFBC symptoms, suggesting homozygous patterns may underlie early-onset disease.

Conclusions:

• Recent findings suggest that homozygous inheritance patterns of genes typically associated with autosomal dominant PFBC may lead to early-onset manifestations.
• Further research, including detailed bioinformatic analysis, is needed to understand the diverse clinical presentations and complex inheritance patterns in PFBC.