0-TESTO COMPLETO.pdf - Fondazione Santa Lucia

TEL.13 – Clinical and laboratory criteria for FSHD diagnosis in view of a national registry…
The evaluation procedure will be divided into six sections that will allow
to assess the strength and the function of muscular groups belonging to:
I) face (score from 0 to 2);
II) shoulder girdle (score from 0 to 3);
III) upper limbs ( score from 0 to 2);
IV) distal legs (0-2) ;
V) pelvic girdle (score from 0 to 5);
VI) abdominal muscles (0-1).
The MRC scale will be used to evaluate muscle strength in affected
muscles.
More detailed information such as asymmetry of presentation, or any
observed peculiarity can be added in the section “ others ”.
This procedure has been selected because it can be easily performed in
the medical office, it is not influenced by the tester, and different investigators
generate comparable results. The six sections of the evaluation procedure are
independent, allowing a precise definition of atypical cases. The uniformity of
the different centers will be guaranteed by a preliminary meeting organized
by the clinical coordinator where details of the clinical assessment will be discussed.
A DVD showing the assessment of the muscle strength will be prepared
and used to train the examiners.
B. Extended Molecular Analysis and clinical evaluation of FSHD Families –
Identification of D4Z4 deletion on chromosome 4q35 in DNA by Southern
blot hybridization with probe p13E-11 is considered the “ golden standard ”
for the diagnosis of FSHD.
Analysis of FSHD families collected over years revealed an unexpectedly
high number of compounds heterozygous patients, if we consider the frequency
of the D4Z4 pathogenic allele as 1 in 20,000. One possible explanation
is the presence of a larger number of asymptomatic individuals carrying the
D4Z4 pathogenic deletion than expected. These individuals, unaware of being
affected, maintain the capability of transmitting the pathogenic allele to their
progeny. It is thus possible that “ non-penetrant gene carrier ” marry a second
“ non-penetrant gene carrier ”. Indeed, clinical study of relatives of the compound
heterozygotes revealed that 51% of subjects carrying the molecular
defect are healthy or asymptomatic.
This observation suggests that the penetrance of the disease, in general
considered almost complete by the age of 20, might be greatly reduced in a
number of subjects, leading to a underestimation of the frequency of FSHD
pathogenic mutation.
By extending the molecular analysis to all asymptomatic subjects of
FSHD families we aim to precisely define the penetrance of FSHD in the Italian
population in correlation with the D4Z4 pathogenic allele size.
C. Molecular Analysis and clinical evaluation of subjects carrying p13E-11alleles
of 38kb-45kb in size – In 1998 [Lunt 1998], as a result of the ENMC workshop
on FSHD, the size of p13-E11 fragments defining a FSHD pathogenic
allele was established. With general consensus, the presence of a p13-E11
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