Myhre syndrome

Clin Genet. 2014 Jun;85(6):503-13. doi: 10.1111/cge.12365. Epub 2014 Apr 2.

Abstract

Myhre syndrome (MS) is a developmental disorder characterized by typical facial dysmorphism, thickened skin, joint limitation and muscular pseudohypertrophy. Other features include brachydactyly, short stature, intellectual deficiency with behavioral problems and deafness. We identified SMAD4 as the gene responsible for MS. The identification of SMAD4 mutations in Laryngotracheal stenosis, Arthropathy, Prognathism and Short stature (LAPS) cases supports that LAPS and MS are a unique entity. The long-term follow up of patients shows that these conditions are progressive with life threatening complications. All mutations are de novo and changing in the majority of cases Ile500, located in the MH2 domain involved in transcriptional activation. We further showed an impairment of the transcriptional regulation via TGFβ target genes in patient fibroblasts. Finally, the absence of SMAD4 mutations in three MS cases may support genetic heterogeneity.

Keywords: LAPS; Myhre; SMAD4; follow up.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cryptorchidism / genetics*
  • Cryptorchidism / pathology
  • Cryptorchidism / physiopathology
  • Disease Progression
  • Facies
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Follow-Up Studies
  • Genetic Heterogeneity*
  • Genotype
  • Growth Disorders / genetics*
  • Growth Disorders / pathology
  • Growth Disorders / physiopathology
  • Hand Deformities, Congenital / genetics*
  • Hand Deformities, Congenital / pathology
  • Hand Deformities, Congenital / physiopathology
  • Humans
  • Hypertrophy / genetics*
  • Hypertrophy / pathology
  • Hypertrophy / physiopathology
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Intellectual Disability / physiopathology
  • Joint Diseases / genetics*
  • Joint Diseases / pathology
  • Joint Diseases / physiopathology
  • Male
  • Mutation*
  • Phenotype
  • Smad4 Protein / chemistry
  • Smad4 Protein / genetics*
  • Transcriptional Activation
  • Transforming Growth Factor beta / genetics

Substances

  • SMAD4 protein, human
  • Smad4 Protein
  • Transforming Growth Factor beta

Supplementary concepts

  • Growth mental deficiency syndrome of Myhre