Table 2 Literature reports based on the use of MOMIS and OPEN CLINICA tools for the Italian FSHD Registry
Momis FSHD platform usage | Participants (n) | Study design | Conclusions |
|---|---|---|---|
Subjects filtered by year: 2008–2013 Subjects filtered by allele: 1 - 3 RUs Subjects filtered by term: proband and relatives Subjects classified using CCEF annotations: category and FSHD score | 66 probands 33 relatives | Subjects carrying 1–3 DRA were searched for disease early onset. Disease outcome was evaluated in de novo and familial probands and their relatives. To investigate the earliest signs of disease, the Infantile Anamnestic Questionnaire (IAQ) was used. Nikolic et al., 2016 | The size of the D4Z4 allele is not always predictive of severe clinical outcome. The high degree of clinical variability suggests that additional factors contribute to the phenotype complexity |
Subjects filtered by year: 2008–2009 Subjects filtered by allele: 1-9 RUs Subjects filtered by geographic location: Modena, Turin, and Naples Subjects classified using CCEF annotations: category and FSHD score | 56 cases | Based on the 7-year experience of the ICNF, the inter-rater reproducibility of the CCEF was assessed between two examiners using kappa statistics in 56 subjects carrying the molecular marker used for FSHD diagnosis. Ricci et al., 2016 | CCEF is an easy clinical tool useful to capture various phenotypes from classic FSHD to individuals with incomplete phenotype, or asymptomatic carriers as well as subjects with atypical signs for which alternative diagnoses may be supposed |
Subjects filtered by year: 2008–2016 Subjects filtered by allele: 7-8 RUs Subjects filtered by term proband and relatives Subjects classified using CCEF annotations: category and FSHD score | 187 probands 235 relatives | Probands and their relatives carrying 7–8 DRA were phenotypically stratified based on the CCEF categories. Ruggiero et al., 2020 | Large phenotypic variability was found in individuals carrying a 7–8 DRA, in contrast to the indication that a positive molecular test is the only determining aspect for FSHD diagnosis. Carriers of a 7–8 DRA constitute a genetic subgroup different from classic FSHD. The use of CCEF and the family study are both required for clinical management and genetic counseling |
Subjects filtered by year: 2008–2016 Subjects filtered by allele: 9-10 RUs Subjects filtered by term: proband and relatives Subjects classified using CCEF annotations: category and FSHD score | 134 probands 110 relatives | Probands and their relatives carrying 9 to 10 DRA were phenotypically stratified based on the CCEF categories. Ricci et al., 2020 | Large phenotypic variability in 9–10 DRA carriers, including 70% of healthy relatives. Penetrance in families ranged between 20–100%. The use of CCEF and the family study are both required for clinical management and genetic counseling. Stratification of patients using the number of D4Z4 RUs is not accurate |
Subjects filtered by term proband and relatives Subjects classified using CCEF annotations: Category and FSHD score Disease progression measured as ΔFSHD score | 141 probands 105 relatives | Subjects were analyzed to estimate the disease worsening calculated as the FSHD score performed at baseline and at the end of 5-year follow-up (ΔFSHD score) Vercelli et al., 2020 | The progression of disease is different between index cases and carrier relatives and the assessment of the CCEF categories has strong prognostic effect in FSHD1 patients |
Subject filtered by clinical category: A1–A3, FSHD score > 1 Subjects filtered by term: proband and relatives Subjects (relatives) classified using CCEF annotations: category and FSHD score | 122 probands 110 relatives | The D4Z4 methylation level at 4q35 was assessed in 122 FSHD1 probands and in relatives carrying the same molecular defect presenting classical FSHD (category A), or incomplete /complex phenotype (categories B or D) or no muscle impairment (category C). Nikolic et al., 2020 | The D4Z4 methylation levels among index cases and in families show a high variability with no association with clinical manifestation or disease progression The results of D4Z4 methylation analysis must be cautiously interpreted in respect to disease prognosis, which requires family studies |
Subjects filtered by term proband Subjects filtered for non-familial cases Subjects filtered by comorbidities/complex phenotypes | 1339 FSHD unrelated cases | Among 1339 unrelated FSHD cases 3 unrelated cases presented signs of Williams-Beuren Syndrome (WBS) in early childhood and later developed FSHD. All 3 cases carry both molecular defects associated with the two disorders. Rodolico et al., 2020 | The rarity of WBS and FSHD, 1 in 7500 and 1 in 20,000 respectively, argued for a nonrandom association of the two diseases. These cases open novel and unexpected interpretation of genetic findings providing hints for the identification of genes and functional pathways involved |