Genotype and phenotype in 12 additional individuals with SATB2-associated syndrome

Area of Science:

• Genetics
• Pediatrics
• Medical Genetics

Background:

• SATB2-associated syndrome (SAS) is a rare genetic disorder.
• It results from pathogenic variants in the SATB2 gene.
• Understanding its phenotype and genotype is crucial for diagnosis and management.

Purpose of the Study:

• To describe the phenotype and genotype of 12 individuals with SAS.
• To review previously reported cases of SAS caused by point alterations.
• To explore early genotype-phenotype correlations in SAS.

Main Methods:

• Phenotypic and genotypic characterization of 12 individuals with SAS.
• Identification of 10 unique pathogenic SATB2 variants (1 splice site, 5 frameshift, 3 nonsense, 2 missense).
• Literature review of published cases of SAS caused by point alterations.

Main Results:

• All 12 individuals presented with developmental delay (DD) and severe speech compromise.
• Facial dysmorphism and dental anomalies were universally observed.
• Tibial bowing was noted in one individual with a truncating SATB2 variant, the third such case reported.

Conclusions:

• SAS is characterized by universal DD with severe speech impediment, mild facial dysmorphism, and frequent craniofacial anomalies.
• Early genotype-phenotype correlations are emerging.
• Further delineation of phenotypic traits and genotype-phenotype correlations is expected with new case identification and adoption of surveillance guidelines.