Myhre syndrome is a rare genetic disorder inherited in an autosomal dominant fashion. It is caused by mutation in

SMAD4 SMAD4, also called SMAD family member 4, Mothers against decapentaplegic homolog 4, or DPC4 (Deleted in Pancreatic Cancer-4) is a highly conserved protein present in all metazoans. It belongs to the SMAD family of transcription factor proteins, ...

gene.

Signs and symptoms

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 * tracheal stenosis *

aortic stenosis Aortic stenosis (AS or AoS) is the narrowing of the exit of the left ventricle of the heart (where the aorta begins), such that problems result. It may occur at the aortic valve as well as above and below this level. It typically gets worse ove ...

pyloric stenosis Pyloric stenosis is a narrowing of the opening from the stomach to the first part of the small intestine (the pylorus). Symptoms include projectile vomiting without the presence of bile. This most often occurs after the baby is fed. The typical a ...

The facial abnormalities include: *

blepharophimosis Blepharophimosis is a congenital anomaly in which the eyelids are underdeveloped such that they cannot open as far as usual and permanently cover part of the eyes. Both the vertical and horizontal palpebral fissures (eyelid openings) are shortene ...

(an abnormally narrow gap between the upper and lower eyelids) * maxillary hypoplasia (underdevelopment of the upper jaw) *

prognathism Prognathism, also called Habsburg jaw or Habsburgs' jaw primarily in the context of its prevalence amongst members of the House of Habsburg, is a positional relationship of the mandible or maxilla to the skeletal base where either of the jaws pr ...

(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.

Genetics

Myhre syndrome is due to mutations in the

gene.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 This gene encodes a protein - transducer mediating transforming growth factor beta. Some researchers believe that the SMAD4 gene mutations that cause Myhre syndrome impair the ability of the SMAD4 protein to attach (bind) properly with the other proteins involved in the signaling pathway. Other studies have suggested that these mutations result in an abnormally stable SMAD4 protein that remains active in the cell longer. Changes in SMAD4 binding or availability may result in abnormal signaling in many cell types, which affects development of several body systems and leads to the signs and symptoms of Myhre syndrome. 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.

Diagnosis

Treatment

History

This disorder was first reported in 1981.Myhre SA, Ruvalcaba RHA, Graham CB (1981) A new growth deficiency syndrome. Clin Genet 20: 1-5 It has many similarities to LAPS Syndrome and they both arise from the same mutations in the SMAD4 gene. It is believed that they are the same syndrome.

References

External links

{{Medical resources , DiseasesDB = , ICD10 = Q87.8 , ICD9 = , ICDO = , OMIM = 139210 , MedlinePlus = , MeSH = , GeneReviewsNBK = , GeneReviewsName = , Orphanet = 2588 , SNOMED CT = 699316006 Rare genetic syndromes Rare syndromes Syndromes affecting the heart Syndromes with craniofacial abnormalities Syndromes with dysmelia Syndromes with short stature Syndromes with musculoskeletal abnormalities Syndromes affecting hearing