KAT6A Syndrome: genotype-phenotype correlation in 76 patients with pathogenic KAT6A variants

Area of Science:

• Genetics
• Developmental Biology
• Clinical Medicine

Background:

• Pathogenic variants in KAT6A are a recently identified cause of syndromic developmental delay.
• The full clinical spectrum and variability of KAT6A syndrome are not yet well-defined.

Purpose of the Study:

• To expand the understanding of the genotypic and phenotypic spectrum of KAT6A syndrome.
• To identify genotype-phenotype correlations and novel clinical associations.

Main Methods:

• Data collection from treating clinicians, an online family survey, and literature review.
• Identification and analysis of unreported and published cases of KAT6A pathogenic variants.

Main Results:

• Identified 52 new cases, totaling 76 published cases.
• Expanded the genotypic spectrum to include missense and splicing mutations.
• Found genotype-phenotype correlations, with late-truncating variants linked to core features and highlighted increased risk for gastrointestinal obstruction.

Conclusions:

• The genotypic and phenotypic spectrum of KAT6A syndrome is expanded.
• Clinical management guidelines for KAT6A syndrome are outlined.