Loeys-Dietz syndrome caused by 1q41 deletion including TGFB2 is associated with a neurodevelopmental phenotype

Am J Med Genet A. 2022 Jul;188(7):2237-2241. doi: 10.1002/ajmg.a.62758. Epub 2022 Apr 15.

Abstract

Loeys-Dietz syndrome (LDS) is a connective tissue disorder that commonly results in a dilated aorta, aneurysms, joint laxity, craniosynostosis, and soft skin that bruises easily. Neurodevelopmental abnormalities are uncommon in LDS. Two previous reports present a total of four patients with LDS due to pure 1q41 deletions involving TGFB2 (Gaspar et al., American Journal of Medical Genetics Part A, 2017, 173, 2289-2292; Lindsay et al., Nature Genetics, 2012, 44, 922-927). The current report describes an additional five patients with similar deletions. Seven of the nine patients present with some degree of hypotonia and gross motor delay, and three of the nine present with speech delay and/or intellectual disability (ID). The smallest deletion common to all patients is a 785 kb locus that contains two genes: RRP15 and TGFB2. Previous studies report that TGFB2 knockout mice exhibit severe perinatal anomalies (Sanford et al., Development, 1997, 124, 2659-2670) and TGFB2 is expressed in the embryonic mouse hindbrain floor (Chleilat et al., Frontiers in Cellular Neuroscience, 2019, 13). The deletion of TGFB2 may be associated with a neurodevelopmental phenotype with incomplete penetrance and variable expression.

Keywords: 1q41 deletion; Loeys-Dietz syndrome; TGFB2; developmental delay; genetic testing.

Publication types

  • Case Reports

MeSH terms

  • Animals
  • Connective Tissue Diseases*
  • Humans
  • Language Development Disorders*
  • Loeys-Dietz Syndrome* / diagnosis
  • Loeys-Dietz Syndrome* / genetics
  • Mice
  • Phenotype
  • Transforming Growth Factor beta2 / genetics

Substances

  • TGFB2 protein, human
  • Transforming Growth Factor beta2