Expansion of the Phenotypic and Genotypic Spectrum of MED13L-Associated Neurodevelopmental Disorder: A Case Report...

Pathogenic variants in MED13L, including copy-number changes and sequence variants, cause MED13L syndrome. This rare neurodevelopmental disorder is characterized by global developmental delay, intellectual disability (ID), distinctive facial dysmorphism, hypotonia, and variable congenital heart defects. The phenotypic heterogeneity of MED13L syndrome underscores the significance of genotype-phenotype correlation analysis for improving clinical diagnosis and precise phenotypic characterization of affected individuals.

Venous blood samples anticoagulated with EDTA were collected from the patient and family members, followed by whole-exome sequencing analysis and subsequent validation using fluorescent quantitative PCR. Concurrently, a systematic search of the PubMed database was performed to summarize previously reported cases harboring MED13L copy number Variations (CNVs).

Whole-exome sequencing revealed a de novo heterozygous single-copy duplication of a ~19-kb region within the MED13L gene (exons 8-16) in the proband. The patient presents phenotypic features consistent with MED13L syndrome and represents the first reported case exhibiting cleft lip. A literature review indicates that vision impairment, developmental delay, and congenital heart disease are widely observed phenotypes, while other less frequent manifestations vary between patients with duplications and deletions.

This study, integrating a case report and a literature review, provides important reference evidence for the clinical genetic counseling of MED13L syndrome.