Targeted gene(s)/phenotype under study

Myhre syndrome:  (OMIM #139210 or ORPHA 2588 )


Myhre syndrome is a connective tissue disorder with multisystem involvement including short stature, progressive and proliferative fibrosis that may occur spontaneously or following trauma or surgery. Most individuals also have variable intellectual disability, and in some instances, autistic-like behavior. Cardiovascular, respiratory, gastrointestinal, and cutaneous involvement are, usually, of clinical concern. Myhre syndrome is caused by gain-of-function variants in SMAD4 (affecting residues p.Arg496 and p.Ile500).

We aim to define the clinical presentation in adulthood. We ask ERN-ITHACA based clinicians to contact us if they would like to share clinical data and facial photographs of individuals with Myhre syndrome aged 18 years old and above. Following consent, individuals/their legal representatives will also be asked to complete the Myhre syndrome association registry (

Coordinating clinicians/researchers 

  • Bert Callewaert
  • Sofia Douzgou Houge
  • Nicola Brunetti-Pierri



  1. Center for Medical Genetics, Ghent University Hospital, Belgium.
  2. Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
  3. Department of Translational Medicine, University of Naples “Federico II”, Italy.

Specific requirements beyond clinical data and genotype data sharing

  • Re-analysis of DNA samples : No
  • Resampling of patients : No
  • Linked to a translational/basic research project? No