[Two cases of Coffin-Siris syndrome type 3 caused by de novoSMARCB1 gene mutations]

Area of Science:

• Genetics
• Pediatrics
• Rare Diseases

Background:

• Coffin-Siris syndrome (CSS) is a rare genetic disorder characterized by intellectual disability, developmental delays, and distinctive facial features.
• CSS is typically caused by mutations in genes involved in the SWI/SNF chromatin remodeling complex.
• Early diagnosis is crucial for appropriate management and genetic counseling.

Purpose of the Study:

• To report two unrelated cases of Coffin-Siris syndrome type 3.
• To identify the genetic cause of the syndrome in these patients.
• To emphasize the role of genetic testing in diagnosing CSS.

Main Methods:

• Clinical phenotyping including detailed medical history and physical examination.
• Genetic testing, specifically whole exome sequencing or targeted gene sequencing.
• Analysis of genetic variants to identify pathogenic mutations.

Main Results:

• Both patients presented with developmental delay, feeding difficulties, hypotonia, and characteristic facial dysmorphia.
• Genetic testing revealed a c.1096C>T heterozygous variant in the SMARCB1 gene in both unrelated individuals.
• This variant was confirmed as the pathogenic mutation responsible for Coffin-Siris syndrome type 3 in both cases.

Conclusions:

• The identification of the same pathogenic SMARCB1 mutation in two unrelated patients reinforces its role in Coffin-Siris syndrome type 3.
• Clinical presentation of CSS can vary, underscoring the need for comprehensive genetic evaluation.
• Early genetic diagnosis facilitates timely intervention and family planning for Coffin-Siris syndrome.