Growth, development, and phenotypic spectrum of individuals with deletions of 2q33.1 involving SATB2

SATB2-Associated syndrome (SAS) is an autosomal dominant, multisystemic, neurodevelopmental disorder due to alterations in SATB2 at 2q33.1. A limited number of individuals with 2q33.1 contiguous deletions encompassing SATB2 (Delta SAS) have been described in the literature. We describe 17 additional individuals with Delta SAS, review the phenotype of 33 previously published individuals with 2q33.1 deletions (n = 50, mean age = 8.5 +/- 7.8 years), and provide a comprehensive comparison to individuals with other molecular mechanisms that result in SAS (non-Delta SAS). Individuals in the Delta SAS group were often underweight for age (20/41 = 49%) with a progressive decline in weight (95% CI = -2.3 to -1.1, p < 0.0001) and height (95% CI = -2.3 to -1.0, p < 0.0001) Z-score means from birth to last available measurement. Delta SAS individuals were often noted to have a broad spectrum of facial dysmorphism. A composite image of Delta SAS individuals generated by automated image analysis was distinct as compared to matched controls and non-Delta SAS individuals. We also present additional genotype-phenotype correlations for individuals in the Delta SAS group such as an increased risk for aortic root/ascending aorta dilation and primary pulmonary hypertension for those individuals with contiguous gene deletions that include COL3A1/COL5A2 and BMPR2, respectively. Based on these findings, we provide additional care recommendations for individuals with Delta SAS variants.

Automated summary

SATB2-Associated syndrome (SAS) is a neurodevelopmental disorder caused by alterations in SATB2 at 2q33.1. Individuals with Delta SAS often exhibit underweight, progressive decline in weight and height, facial dysmorphism, and unique facial features compared to non-Delta SAS individuals. Additionally, Delta SAS individuals have increased risks for aortic root/ascending aorta dilation and primary pulmonary hypertension due to specific gene deletions. Care recommendations for individuals with Delta SAS variants are provided based on these findings.