Infantile spasms are associated with abnormal copy number variations

Area of Science:

• Genetics
• Pediatric Neurology

Background:

• Infantile spasms are a severe epilepsy syndrome in infants.
• The genetic underpinnings of infantile spasms are complex and not fully understood.
• Copy number variations (CNVs) are known to cause various genomic disorders.

Purpose of the Study:

• To test the hypothesis that de novo pathogenic CNVs contribute to infantile spasms.
• To identify specific CNVs associated with infantile spasms in affected children.

Main Methods:

• Genome-wide analysis of single-nucleotide polymorphism genotyping microarray data.
• Analysis of 13 trios (child and both parents) affected by infantile spasms.
• Identification and characterization of de novo and known pathogenic large CNVs.

Main Results:

• A rare, large de novo duplication (4.8 Mb) in the 15q11-13 region was identified in one patient.
• Three known pathogenic CNVs were detected in total, present in both the child and a parent.
• Specific pathogenic deletions were found in regions 2q32.3, 16p11.2, and Xp22.13 (including CDKL5) in affected individuals.

Conclusions:

• Specific pathogenic CNVs are significant predisposing factors for infantile spasms.
• These CNVs may be associated with diverse clinical phenotypes in infantile spasms.
• Further research into CNVs is warranted for understanding infantile spasms etiology.