Myhre syndrome

Myhre syndrome (MS) is an ultra-rare autosomal dominant disorder due to a narrow spectrum of mutations in SMAD4 that encodes a member of TGFβ pathway that regulates extra-cellular matrix (ECM) homeostasis. Core clinical features of MS are related to progressive fibrosis and include thickening of skin and joint stiffness.
The Italian Telethon Undiagnosed Diseases Program (TUDP) has provided molecular diagnoses by whole exome sequencing (WES) in a growing number of patients. A 2-year-old girl with growth deficiency, dysmorphic features, tetralogy of Fallot, and a congenital eye defect was among the first patients enrolled in the program. She was diagnosed as the youngest patient with MS by detection of the recurrent p.Ile500Val mutation in the SMAD4 gene.  
As our group had previously shown that the anti-hypertensive drug losartan improves TGFβ signalling and the ECM defect in MS fibroblasts, we propose the administration of the anti-hypertensive drug losartan to MS patients. Our project aims to define clinical endpoints and biomarkers that can be used to monitor disease progression and efficacy of experimental treatments in MS. Preliminary data suggest that losartan might be effective in improving sclerosis-related manifestations of MS.

The "Total Award" amount indicated for this project represents the share of the funding of the Telethon Foundation for research by the Tigem institute from July 2016 until last budget year, calculated based on the size of the research group.