“Clinical and laboratory criteria for Facioscapulohumeral muscular dystrophy
(FSHD) diagnosis in view of a national registry for the disease”
Facioscapulohumeral muscular dystrophy (FSHD) is a common myopathy. The disease affects specific muscles, thus patients are not able to close their eyes, blow their chicks, lift their arms and, eventually, may become wheelchair dependent.
FSHD is an autosomal-dominant inherited disorder, therefore each child has a 50% chance of inheriting the disease from an affected parent.
The disease has been associated to the reduction of a string of DNA elements, named D4Z4, that is located at the tip of chromosome 4 long arm. When the string of DNA is too short the disease appears.
95% of FSHD patients carry a reduced number of D4Z4 units.
Molecular analysis allows counting number of the D4Z4 repeat units on each chromosome 4 and is used to detect carriers of the molecular defect. Nowadays, this test is considered diagnostic for the disease.
It is noteworthing that FSHD can appear with different degree of severity and it is not clear how individuals carrying the same short string of DNA elements, even within the same family, will develop the disease. For this reason, it could be difficult to distinguish, through a neurological evaluation, which subjects carry the genetic defect. In fact, within the same family there could be subjects unable to walk and siblings unaware of carrying the genetic defect.
Here we propose an objective clinical study of familiar and sporadic cases in which the genetic defect characteristic of FSHD has been detected.
This study will also consider patients showing FSHD clinical features without having the molecular defect with the aim of identifyig molecular markers useful for diagnosis
Telethon project GUP07001 includes the majority of the Italian Centers for Neuromuscular disorders. The project aims to collect clinical and anamnestic data through a specifically designed form. These data will generate a score (FSHD score) that quantifies the severity of the disease.
This specific form has already been validated by the medical litterature, and we aim to make our data collection uniform through all the clinical centers involved.
The goal of our study is to delineate the different clinical descriptions that appear in FSHD phenotype, and to correlate the number of repeat units present in patients’ genotype with their clinical features observed.
We expect to define some aspects of the disease progression and gain useful information to improve our prognostic tools.
The study will evaluate over 500 FSHD families, collecting several anamnesic data to facilitate the identification of factors that can influence the disease onset and progression.
In order to obtain an FSHD score from a uniform examination of patients, clinical practice guidelines have been included in a DVD
The collection of all clinical and molecular data will be integrated in a dedicated database that will represent a powerful tool for data elaboration. The database will be associated with the creation of the National Registry of FSHD.