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SATB2-associated syndrome (SAS) is an autosomal dominant disorder characterized by significant neurodevelopmental disabilities with limited to absent speech, behavioral issues, and craniofacial anomalies. Previous studies have largely been restricted to case reports and small series without in-depth phenotypic characterization or genotype-phenotype correlations. Seventy two study participants were identified as part of the SAS clinical registry. Individuals with a molecularly confirmed diagnosis of SAS were referred after clinical diagnostic testing. In this series we present the most comprehensive phenotypic and genotypic characterization of SAS to date, including prevalence of each clinical feature, neurodevelopmental milestones, and when available, patient management. We confirm that the most distinctive features are neurodevelopmental delay with invariably severely limited speech, abnormalities of the palate (cleft or high-arched), dental anomalies (crowding, macrodontia, abnormal shape), and behavioral issues with or without bone or brain anomalies. This comprehensive clinical characterization will help clinicians with the diagnosis, counseling and management of SAS and help provide families with anticipatory guidance., (© 2018 Wiley Periodicals, Inc.)

The SATB2-associated syndrome (SAS) was recently proposed as a clinically recognizable syndrome that results from deleterious alterations of the SATB2 gene in humans. Although interstitial deletions at 2q33 encompassing SATB2, either alone or contiguously with other genes, have been reported before, there is limited literature regarding intragenic mutations of this gene and the resulting phenotype. We describe five patients in whom whole exome sequencing identified five unique de novo mutations in the SATB2 gene (one splice site, one frameshift, and three nonsense mutations). The five patients had overlapping features that support the characteristic features of the SAS: intellectual disability with limited speech development and craniofacial abnormalities including cleft palate, dysmorphic features, and dental abnormalities. Furthermore, Patient 1 also had features not previously described that represent an expansion of the phenotype. Osteopenia was seen in two of the patients, suggesting that this finding could be added to the list of distinctive findings. We provide supporting evidence that analysis for deletions or point mutations in SATB2 should be considered in children with intellectual disability and severely impaired speech, cleft or high palate, teeth abnormalities, and osteopenia., (© 2015 Wiley Periodicals, Inc.)