Myhre syndrome

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Myhre syndrome is a rare genetic disorder.


This disorder was first reported in 1981.[1]


It is inherited as an autosomal dominant disorder.

It is due to mutations in the SMAD4 gene.[2] This gene encodes a protein - transducer mediating transforming growth factor beta.

The patients of this disease exhibit hypertrophic phenotype in their muscle tissues. Myostatin target genes are found to be downregulated while bone morphogenetic protein (BMP) target genes display both upregulated and downregulated genotypes. [3]


The clinical presentation is variable but includes

  • developmental and growth delay
  • athletic muscular built
  • skeletal anomalies
  • joint stiffness
  • characteristic facial appearance
  • deafness
  • variable cognitive deficits

The facial abnormalities include:

  • blepharophimosis (an abnormally narrow gap between the upper and lower eyelids)
  • maxillary hypoplasia (underdevelopment of the upper jaw)
  • prognathism (prominent lower jaw)

The skeletal abnormalities include:

  • short stature
  • square body shape
  • broad ribs
  • iliac hypoplasia
  • brachydactyly
  • flattened vertebrae
  • thickened calvaria

Congenital heart disease and undescended testes have also been reported in association with this syndrome.


  1. ^ Myhre SA, Ruvalcaba RHA, Graham CB (1981) A new growth deficiency syndrome. Clin Genet 20: 1-5
  2. ^ Caputo V, Bocchinfuso G, Castori M, Traversa A, Pizzuti A, Stella L, Grammatico P, Tartaglia M (2014) Novel SMAD4 mutation causing Myhre syndrome. Am J Med Genet A doi: 10.1002/ajmg.a.36544
  3. ^ Le Goff, Carine. et al. (2012). "Mutations at a single codon in Mad homology 2 domain of SMAD4 cause Myhre syndrome". NATURE GENETICS 44: 85–88.