A pilot clinical trial with losartan in Myhre syndrome.
Adolescent
Adult
Angiotensin II Type 1 Receptor Blockers
/ therapeutic use
Child
Child, Preschool
Cryptorchidism
/ drug therapy
Facies
Female
Follow-Up Studies
Growth Disorders
/ drug therapy
Hand Deformities, Congenital
/ drug therapy
Humans
Intellectual Disability
/ drug therapy
Losartan
/ therapeutic use
Male
Pilot Projects
Prognosis
Young Adult
Myhre syndrome
SMAD4
TGF-beta
losartan
systemic sclerosis
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
06
07
2020
revised:
23
11
2020
accepted:
24
11
2020
pubmed:
29
12
2020
medline:
3
8
2021
entrez:
28
12
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 33369056
doi: 10.1002/ajmg.a.62019
pmc: PMC7898344
doi:
Substances chimiques
Angiotensin II Type 1 Receptor Blockers
0
Losartan
JMS50MPO89
Types de publication
Case Reports
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
702-709Informations de copyright
© 2020 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
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