SATB2-associated syndrome presenting with Rett-like phenotypes

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Syndromology

Background:

• SATB2-associated syndrome (SAS) is a recently defined genetic disorder linked to the SATB2 gene, primarily known for intellectual disability, speech delay, and craniofacial anomalies.
• Initial research connected SATB2 mutations to isolated cleft palate, leading to the characterization of SAS with specific developmental and physical features.

Observation:

• This study reports two unrelated patients with severe psychomotor retardation and Rett-like phenotypes, presenting novel sequence variants in the SATB2 gene.
• Whole-exome sequencing identified a de novo missense variant (p.Glu396Gln) in one patient, while targeted sequencing revealed a nonsense variant (p.Arg459*) in the second patient.

Findings:

• The identified SATB2 variants expand the known clinical and genetic spectrum of SATB2-associated syndrome.
• The findings suggest that SAS should be considered in individuals with psychomotor retardation or Rett-like phenotypes, even in the absence of classic SAS features like cleft palate.

Implications:

• These discoveries broaden the diagnostic criteria for SATB2-associated syndrome.
• Clinicians should consider SATB2 gene analysis in a wider range of neurodevelopmental and neurological presentations, enhancing diagnostic yield for rare genetic conditions.