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Myhre syndrome
Author(s) -
Le Goff C.,
Michot C.,
CormierDaire V.
Publication year - 2014
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12365
Subject(s) - short stature , brachydactyly , medicine , mutation , facial dysmorphism , genetic disorder , prognathism , laryngotracheal stenosis , genetics , gene , bioinformatics , biology , stenosis , phenotype , tracheal stenosis , surgery , osteotomy
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.