Homozygous deletion of exons 2-7 within TGFB3 gene in a child with severe Loeys-Dietz syndrome and Marfan-like features

Am J Med Genet A. 2020 May;182(5):1230-1235. doi: 10.1002/ajmg.a.61508. Epub 2020 Feb 5.


We describe a patient with palatal abnormalities-cleft palate and bifid uvula; distinctive facial features-long and triangular face, large ears and nose, thin lips and dental crowding; musculoskeletal abnormalities-severe scoliosis, joint laxity, long digits, flat feet, decreased muscle mass, and diminished muscle strength; and cardiac features-a dilatated ascending aorta at the level of Valsalva sinuses and a patent foramen ovale. Sequence analysis and deletion/duplication testing for a panel of genes involved in connective tissue disorders revealed the presence of a novel homozygous deletion of exons 2-7 in TGFB3 gene. Heterozygous pathogenic mutations in TGFB3 have been associated with Loeys-Dietz syndrome 5 (LDS5) and Arrhythmogenic Right Ventricular Dysplasia type 1. Here, we report the first case of a homozygous TGFB3 variant associated with a severe LDS5 and Marfan-like presentation.

Keywords: TGFB3; Loeys-Dietz; Marfan syndrome; dysmorphology; marfanoid habitus; scoliosis.

Publication types

  • Case Reports

MeSH terms

  • Arrhythmogenic Right Ventricular Dysplasia / diagnostic imaging
  • Arrhythmogenic Right Ventricular Dysplasia / genetics*
  • Arrhythmogenic Right Ventricular Dysplasia / physiopathology
  • Child
  • Child, Preschool
  • Exons / genetics
  • Gene Deletion
  • Genetic Predisposition to Disease
  • Homozygote
  • Humans
  • Infant
  • Loeys-Dietz Syndrome / diagnostic imaging
  • Loeys-Dietz Syndrome / genetics*
  • Loeys-Dietz Syndrome / physiopathology
  • Male
  • Marfan Syndrome / diagnostic imaging
  • Marfan Syndrome / genetics*
  • Marfan Syndrome / physiopathology
  • Mutation / genetics
  • Sequence Deletion / genetics
  • Transforming Growth Factor beta3 / genetics*


  • TGFB3 protein, human
  • Transforming Growth Factor beta3