TY - JOUR
T1 - Clinical expression of facioscapulohumeral muscular dystrophy in carriers of 1-3 D4Z4 reduced alleles
T2 - Experience of the FSHD Italian National Registry
AU - Nikolic, Ana
AU - Ricci, Giulia
AU - Sera, Francesco
AU - Bucci, Elisabetta
AU - Govi, Monica
AU - Mele, Fabiano
AU - Rossi, Marta
AU - Ruggiero, Lucia
AU - Vercelli, Liliana
AU - Ravaglia, S.
AU - Brisca, Giacomo
AU - Fiorillo, Chiara
AU - Villa, Luisa
AU - Maggi, Lorenzo
AU - Cao, Michelangelo
AU - D'Amico, Maria Chiara
AU - Siciliano, Gabriele
AU - Antonini, Giovanni
AU - Santoro, Lucio
AU - Mongini, T.
AU - Moggio, Maurizio Gualtiero
AU - Morandi, Lucia
AU - Pegoraro, E.
AU - Angelini, Corrado
AU - Di Muzio, A.
AU - Rodolico, C.
AU - Tomelleri, Giuliano
AU - D'Angelo, Maria Grazia
AU - Bruno, Claudio
AU - Berardinelli, Angela Lucia
AU - Tupler, Rossella
PY - 2016
Y1 - 2016
N2 - Objectives: Facioscapulohumeral muscular dystrophy type 1 (FSHD1) has been genetically linked to reduced numbers (≤8) of D4Z4 repeats at 4q35. Particularly severe FSHD cases, characterised by an infantile onset and presence of additional extra-muscular features, have been associated with the shortest D4Z4 reduced alleles with 1-3 repeats (1-3 DRA). We searched for signs of perinatal onset and evaluated disease outcome through the systematic collection of clinical and anamnestic records of de novo and familial index cases and their relatives, carrying 1-3 DRA. Setting: Italy. Participants: 66 index cases and 33 relatives carrying 1-3 DRA. Outcomes: The clinical examination was performed using the standardised FSHD evaluation form with validated inter-rater reliability. To investigate the earliest signs of disease, we designed the Infantile Anamnestic Questionnaire (IAQ). Comparison of age at onset was performed using the non-parametric Wilcoxon rank-sum or Kruskal-Wallis test. Comparison of the FSHD score was performed using a general linear model and Wald test. Kaplan-Meier survival analysis was used to estimate the age-specific cumulative motor impairment risk. Results: No patients had perinatal onset. Among index cases, 36 (54.5%) showed the first signs by 10 years of age. The large majority of patients with early disease onset (26 out of 36, 72.2%) were de novo; whereas the majority of patients with disease onset after 10 years of age were familial (16, 53.3%). Comparison of the disease severity outcome between index cases with age at onset before and over 10 years of age, failed to detect statistical significance (Wald test p value=0.064). Of 61 index cases, only 17 (27.9%) presented extra-muscular conditions. Relatives carrying 1-3 DRA showed a large clinical variability ranging from healthy subjects, to patients with severe motor impairment. Conclusions: 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.
AB - Objectives: Facioscapulohumeral muscular dystrophy type 1 (FSHD1) has been genetically linked to reduced numbers (≤8) of D4Z4 repeats at 4q35. Particularly severe FSHD cases, characterised by an infantile onset and presence of additional extra-muscular features, have been associated with the shortest D4Z4 reduced alleles with 1-3 repeats (1-3 DRA). We searched for signs of perinatal onset and evaluated disease outcome through the systematic collection of clinical and anamnestic records of de novo and familial index cases and their relatives, carrying 1-3 DRA. Setting: Italy. Participants: 66 index cases and 33 relatives carrying 1-3 DRA. Outcomes: The clinical examination was performed using the standardised FSHD evaluation form with validated inter-rater reliability. To investigate the earliest signs of disease, we designed the Infantile Anamnestic Questionnaire (IAQ). Comparison of age at onset was performed using the non-parametric Wilcoxon rank-sum or Kruskal-Wallis test. Comparison of the FSHD score was performed using a general linear model and Wald test. Kaplan-Meier survival analysis was used to estimate the age-specific cumulative motor impairment risk. Results: No patients had perinatal onset. Among index cases, 36 (54.5%) showed the first signs by 10 years of age. The large majority of patients with early disease onset (26 out of 36, 72.2%) were de novo; whereas the majority of patients with disease onset after 10 years of age were familial (16, 53.3%). Comparison of the disease severity outcome between index cases with age at onset before and over 10 years of age, failed to detect statistical significance (Wald test p value=0.064). Of 61 index cases, only 17 (27.9%) presented extra-muscular conditions. Relatives carrying 1-3 DRA showed a large clinical variability ranging from healthy subjects, to patients with severe motor impairment. Conclusions: 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.
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U2 - 10.1136/bmjopen-2015-007798
DO - 10.1136/bmjopen-2015-007798
M3 - Article
VL - 6
JO - BMJ Open
JF - BMJ Open
SN - 2044-6055
IS - 1
M1 - e007798
ER -