0-TESTO COMPLETO.pdf - Fondazione Santa Lucia

Sezione III: Attività per progetti
Intriguingly, the variable penetrance observed in the FSHD population
may be the result of the interaction of several factors such as the repeat array
size, the individuals’ genetic background, and environmental factors. Indeed
the presence of low-penetrant alleles suggest that susceptibility for FSHD is
not only determined by the intrinsic properties of the diseased allele but also
by modifiers present in individual genetic background and/or environment.
Here we propose a research project aimed at analyzing the genetic
aspects described above in a large group of FSHD families and sporadic
patients collected over a 14-year period in order to verify the frequency of
those phenomena. Accurate analysis of family history and patients’ records
will provide relevant information to implement FSHD diagnosis, prognosis
and related genetic counseling.
Moreover, the precise clinical characterization of these families will contribute
to the understanding of the complex pathogenic mechanism of FSHD
and provide new tools to approach this complex disorder.
PRELIMINARY RESULTS
Patients – Patients’ information and samples are available at the neuromuscular
databases of each participating center.
Patients were collected over a 14-years period (1993-2007).
The diagnosis of facioscapulohumeral myopathy, according to the consortium
criteria was based on the presence of: facial weakness, prominent scapular
winging with anterior rotation of the scapula, usually associated with a
proximal myopathy, autosomal dominant inheritance in familial cases and
signs of myopathy in EMG and muscle biopsy in at least one affected member.
Muscle biopsy must rule out alternative diagnoses, such as metabolic
myopathies, mitochondrial diseases, congenital myopathies, polymyositis,
motor neuron disease and all the other muscular dystrophies.
Clinical Protocol – FSHD variable onset and unpredictable progression, associated
with its high clinical variability even within the same family and the
presence of non-penetrant gene carriers, suggest that many factors can influence
the disease outcome. These considerations prompted us to design a clinical
data questionnaire to evaluate FSHD patients and their relatives. The
main purpose of the questionnaire is to gather information about the onset
and evolution of the disease and correlate the disease history with events
occurring in the life of the patient. Several questions have been introduced
based on sporadic observations collected by the diverse clinicians. These
observations are related to medical conditions or events that have been associated
by the patients with sudden worsening of the disease or, in some cases,
with the sudden awareness of being weak. In other words, through the
patients’ anamnestic records we aim at identifying factors/conditions that can
influence the onset and progression of the disease (e.g. pregnancy and
menopause in women affected by FSHD, the use of hormone therapy, etc).
We also generated a clinical evaluation form that allows determining the
FSHD clinical score of each subject carrying a D4Z4 pathogenic allele. The
770 2009