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

Clin Genet. 2021 Apr;99(4):547-557. doi: 10.1111/cge.13912. Epub 2021 Jan 13.

Abstract

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 (ΔSAS) have been described in the literature. We describe 17 additional individuals with ΔSAS, 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-ΔSAS). Individuals in the ΔSAS 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. ΔSAS individuals were often noted to have a broad spectrum of facial dysmorphism. A composite image of ΔSAS individuals generated by automated image analysis was distinct as compared to matched controls and non-ΔSAS individuals. We also present additional genotype-phenotype correlations for individuals in the ΔSAS 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 ΔSAS variants.

Keywords: 2q33.1 deletion; SATB2; SATB2-associated syndrome; facial recognition technology; genotype-phenotype correlation; glass syndrome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Child
  • Child, Preschool
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 2 / genetics*
  • Chromosomes, Human, Pair 2 / ultrastructure
  • Collagen Type III / deficiency
  • Collagen Type III / genetics
  • Collagen Type V / deficiency
  • Collagen Type V / genetics
  • Dwarfism / genetics
  • Face / abnormalities
  • Female
  • Genetic Association Studies
  • Gestational Age
  • Humans
  • Hypertension, Pulmonary / genetics
  • Infant
  • Male
  • Matrix Attachment Region Binding Proteins / deficiency*
  • Matrix Attachment Region Binding Proteins / genetics
  • Microcephaly / genetics
  • Phenotype
  • Thinness / genetics
  • Transcription Factors / deficiency*
  • Transcription Factors / genetics

Substances

  • COL3A1 protein, human
  • Collagen Type III
  • Collagen Type V
  • Matrix Attachment Region Binding Proteins
  • SATB2 protein, human
  • Transcription Factors