A pilot clinical trial with losartan in Myhre syndrome

Am J Med Genet A. 2021 Mar;185(3):702-709. doi: 10.1002/ajmg.a.62019. Epub 2020 Dec 24.


Introduction: Myhre syndrome (MS) is an ultra-rare disorder due to pathogenic variants in the SMAD4 gene that encodes a protein regulating the TGF-β pathway and extra-cellular matrix (ECM) homeostasis. Main clinical features of MS include thickening of skin and joint stiffness. Previous studies showed that losartan improved ECM deposition in MS fibroblasts.

Materials and methods: Four molecularly confirmed MS subjects (mean age 23.8 ± 17 years) were evaluated for: (a) skin thickness by Rodnan score, (b) joint range of motion (ROM) by goniometry, and (c) speckle-tracking echocardiogram. Following baseline evaluations, three MS individuals received losartan for 12 months and pre-defined endpoints were monitored after 6 and 12 months of treatment.

Results: At baseline, Rodnan scores were increased, joint ROM was reduced, and speckle-tracking echocardiogram revealed reduced myocardial strain. In three MS subjects, improvements in skin thickness, joint ROM and to a lesser extent of myocardial strain, were observed after 6 and 12 months of losartan treatment.

Conclusions: Although further long-term controlled clinical trials with a larger number of affected individuals are needed, the present study suggests that losartan might improve skin, joint and heart abnormalities of MS.

Keywords: Myhre syndrome; SMAD4; TGF-beta; losartan; systemic sclerosis.

Publication types

  • Case Reports
  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Child
  • Child, Preschool
  • Cryptorchidism / drug therapy*
  • Cryptorchidism / pathology
  • Facies
  • Female
  • Follow-Up Studies
  • Growth Disorders / drug therapy*
  • Growth Disorders / pathology
  • Hand Deformities, Congenital / drug therapy*
  • Hand Deformities, Congenital / pathology
  • Humans
  • Intellectual Disability / drug therapy*
  • Intellectual Disability / pathology
  • Losartan / therapeutic use*
  • Male
  • Pilot Projects
  • Prognosis
  • Young Adult


  • Angiotensin II Type 1 Receptor Blockers
  • Losartan

Supplementary concepts

  • Growth mental deficiency syndrome of Myhre