Ptosis as a unique hallmark for autosomal recessive WNT1-associated osteogenesis imperfecta

Am J Med Genet A. 2019 Jun;179(6):908-914. doi: 10.1002/ajmg.a.61119. Epub 2019 Mar 21.

Abstract

Osteogenesis imperfecta (OI) is a heritable connective tissue disorder, mainly characterized by bone fragility and low bone mass. Defects in the type I procollagen-encoding genes account for the majority of OI, but increasingly more rare autosomal recessive (AR) forms are being identified, which are caused by defects in genes involved in collagen metabolism, bone mineralization, or osteoblast differentiation. Bi-allelic mutations in WNT1 have been associated with a rare form of AR OI, characterized by severe osteoporosis, vertebral compression, scoliosis, fractures, short stature, and variable neurological problems. Heterozygous WNT1 mutations have been linked to autosomal dominant early-onset osteoporosis. In this study, we describe the clinical and molecular findings in 10 new patients with AR WNT1-related OI. Thorough revision of the clinical symptoms of these 10 novel patients and previously published AR WNT1 OI cases highlight ptosis as a unique hallmark in the diagnosis of this OI subtype.

Keywords: WNT1; collagen; osteogenesis imperfecta; ptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Blepharoptosis / genetics*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Facies
  • Female
  • Genes, Recessive*
  • Genetic Association Studies*
  • Genotype
  • Humans
  • Infant
  • Male
  • Mutation*
  • Osteogenesis Imperfecta / diagnosis*
  • Osteogenesis Imperfecta / genetics*
  • Pedigree
  • Phenotype
  • Radiography
  • Wnt1 Protein / genetics*

Substances

  • WNT1 protein, human
  • Wnt1 Protein