Brain calcification in congenital heart defects and ectodermal dysplasia (CHDED)

Area of Science:

• Genetics
• Neurology
• Developmental Biology

Background:

• Congenital Heart Defect and Ectodermal Dysplasia (CHDED) is a rare autosomal dominant disorder.
• It is characterized by congenital heart defects and ectodermal dysplasia, linked to the PRKD1 gene.
• The full spectrum of organ involvement, particularly calcifications, in CHDED remains incompletely understood.

Observation:

• A 9-month-old Japanese girl with CHDED presented with heart defects and ectodermal dysplasia.
• She developed generalized seizures at 6 months of age.
• A CT scan revealed bilateral deep cerebral white matter calcifications, which resolved with levetiracetam treatment.

Findings:

• The patient harbored a de novo, heterozygous pathogenic variant (c.1808G>A, p.(Arg603His)) in the PRKD1 gene.
• This case, along with prior reports, strengthens the association between PRKD1 variants and brain calcifications in CHDED.
• Experimental data suggests PRKD1 interacts with ITGB2 and JAM2, genes implicated in brain calcification and endothelial cell tight junctions.

Implications:

• The PRKD1 gene variant may directly contribute to the pathological phenotype of brain calcification.
• PRKD1, ITGB2, and JAM2 might act through a shared signaling pathway to influence brain calcification.
• Further research into this pathway could reveal novel therapeutic targets for brain calcification disorders.