A pilot clinical trial with losartan in Myhre syndrome.
Am J Med Genet A
; 185(3): 702-709, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-33369056
ABSTRACT
INTRODUCTION:
Myhre syndrome (MS) is an ultra-rare disorder due to pathogenic variants in the SMAD4 gene that encodes a protein regulating the TGF-ß 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 ANDMETHODS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Deformidades Congênitas da Mão
/
Losartan
/
Criptorquidismo
/
Bloqueadores do Receptor Tipo 1 de Angiotensina II
/
Transtornos do Crescimento
/
Deficiência Intelectual
Tipo de estudo:
Clinical_trials
/
Observational_studies
/
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Female
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Humans
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Male
Idioma:
En
Revista:
Am J Med Genet A
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Itália