Clinical and Genetic Findings in Two Japanese Individuals With SET-Related Neurodevelopmental Disorder

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Human Phenomics

Background:

• SET-related neurodevelopmental disorder (OMIM #618106) is an emerging condition with an incompletely defined phenotypic spectrum.
• Genetic alterations affecting the SET gene are implicated in neurodevelopmental impairment.

Purpose of the Study:

• To further delineate the clinical spectrum of SET-related neurodevelopmental disorder.
• To characterize the phenotypes associated with distinct genomic alterations affecting the SET gene.

Main Methods:

• Case report of two unrelated Japanese individuals with distinct genomic alterations (de novo frameshift variant, microdeletion) affecting the SET gene.
• Phenotypic characterization including global developmental delay, intellectual disability, craniofacial features, and behavioral assessments.
• Comparison with previously reported cases with various SET gene alterations.

Main Results:

• Both individuals presented with global developmental delay, intellectual disability, and overlapping craniofacial features (broad nasal bridge/tip, wide mouth, periorbital fullness).
• A sociable behavioral tendency was noted, but formal diagnoses like autism spectrum disorder or ADHD were not consistently identified.
• Neurodevelopmental impairment is a consistent feature across different SET gene alterations, while craniofacial and behavioral findings show variability.

Conclusions:

• These findings expand the understanding of SET-related neurodevelopmental disorder's clinical spectrum.
• Consistent neurodevelopmental impairment underscores the importance of genetic testing for SET gene alterations in relevant cases.
• Careful phenotypic characterization is crucial for the recognition and diagnosis of SET-related neurodevelopmental disorder.