De novo exon 1 missense mutations of SKI and Shprintzen-Goldberg syndrome: two new cases and a clinical review

Am J Med Genet A. 2014 Mar;164A(3):676-84. doi: 10.1002/ajmg.a.36340. Epub 2013 Dec 19.

Abstract

Shprintzen-Goldberg syndrome (OMIM #182212) is a connective tissue disorder characterized by craniosynostosis, distinctive craniofacial features, skeletal abnormalities, marfanoid body habitus, aortic dilatation, and intellectual disability. Mutations in exon 1 of SKI have recently been identified as being responsible for approximately 90% of reported individuals diagnosed clinically with Shprintzen-Goldberg syndrome. SKI is a known regulator of TGFβ signaling. Therefore, like Marfan syndrome and Loeys-Dietz syndrome, Shprintzen-Goldberg syndrome is likely caused by deregulated TGFβ signals, explaining the considerable phenotypic overlap between these three disorders. We describe two additional patients with exon 1 SKI mutations and review the clinical features and literature of Shprintzen-Goldberg syndrome.

Keywords: Loeys-Dietz; Marfan; SKI protein; Shprintzen-Goldberg; aortic diseases; craniosynostosis; human; transforming growth factor beta.

Publication types

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

MeSH terms

  • Arachnodactyly / diagnosis*
  • Arachnodactyly / genetics*
  • Brain / pathology
  • Child, Preschool
  • Craniosynostoses / diagnosis*
  • Craniosynostoses / genetics*
  • DNA-Binding Proteins / genetics*
  • Exons*
  • Facies
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Marfan Syndrome / diagnosis*
  • Marfan Syndrome / genetics*
  • Mutation, Missense*
  • Phenotype
  • Proto-Oncogene Proteins / genetics*
  • Spinal Cord / pathology
  • Tomography, X-Ray Computed

Substances

  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • SKI protein, human

Supplementary concepts

  • Shprintzen Golberg craniosynostosis