0-TESTO COMPLETO.pdf - Fondazione Santa Lucia

Sezione III: Attività per progetti
discoveries. We expect meticulous clinical evaluation of “ typical ” and “ atypical
” FSHD cases associated with histological and molecular analysis to provide
valuable information for clinicians and researchers. A precise and
updated clinical definition associated with molecular diagnosis is also the
necessary background to identify factors that can influence the disease outcome.
In addition, this study will establish the validity of the FSHD score as a
fundamental tool that can be used to gauge the efficacy of treatments in clinical
trials and test possible future therapeutic approaches.
A. Clinical evaluation of familial and sporadic FSHD subjects – In order to collect
clinical information suitable for statistical analysis, it is critical to achieve
a homogeneous approach for the patients’ evaluation and data collection. To
this aim a specific clinical data questionnaire has been created. It will be
applied by all the clinical centers when interviewing and visiting each single
patient and his/her relatives.
Before the beginning of the study the clinical coordinator will organize a
meeting with participating centers where all the details will be discussed.
Each center will identify one or more examiners who will be specifically
trained and devoted to the collection of patients and families, administration
of the questionnaire and neurological examination. Clinician will be trained
at the use of the clinical evaluation scale. Patients and their family members
will be enrolled through the databases of the single centers. This preliminary
step is relatively easy to achieve, as all participating clinical centers have an
outpatients clinic where patients are regularly seen for follow-ups, or come
for counseling and to address daily problems. Thanks to the good relationship
between clinicians and patients, recruiting family members for genetic analysis
will be relatively straightforward too. Contacts will be made through telephone
calls or mail, explaining the reasons of the study, and appointments
will be made, trying to summon family groups together and drawing an extensive
family tree of each group.
The clinical data questionnaire focuses on the patient’s clinical history,
used drugs, medical conditions and associated pathologies. It will support the
physician and help him/her to collect information, which can be relevant to
identify factors that can influence the disease onset and progression. Moreover
the use of the FSHD score will provide a tool to estimate the penetrance
of the disease in correlation with number of repeats, age and sex. Our intent is
to identify the correlations, if any, between the genetic arrangement and factors,
which may influence the severity of the disease. Family history will be
taken into particular consideration in familial cases, and molecular analysis
will be extended to all first-degree relatives of affected patients. This approach
will allow us to identify asymptomatic carriers and will provide information
suitable to evaluate penetrance of the pathogenic mutation in correlation with
the size of deleted alleles.
To obtain a functional quantification of muscle weakness in FSHD
patients, an evaluation scale specifically modified for FSHD has been
designed based on the Brook et al evaluation scale [Brook et al. 1981] and
modified by Ricci et al. [1999] and Trevisan et al. [2006].
774 2009