Clinical expression of facioscapulohumeral muscular dystrophy in carriers of 1-3 D4Z4 reduced alleles: experience of the FSHD Italian National Registry
UMass Chan Affiliations
Department of Molecular, Cell and Cancer BiologyDocument Type
Journal ArticlePublication Date
2016-01-05Keywords
Cell BiologyMolecular Biology
Molecular Genetics
Musculoskeletal Diseases
Nervous System Diseases
Metadata
Show full item recordAbstract
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.Source
Nikolic A, Ricci G, Sera F, Bucci E, Govi M, Mele F, Rossi M, Ruggiero L, Vercelli L, Ravaglia S, Brisca G, Fiorillo C, Villa L, Maggi L, Cao M, D'Amico MC, Siciliano G, Antonini G, Santoro L, Mongini T, Moggio M, Morandi L, Pegoraro E, Angelini C, Di Muzio A, Rodolico C, Tomelleri G, Grazia D'Angelo M, Bruno C, Berardinelli A, Tupler R. Clinical expression of facioscapulohumeral muscular dystrophy in carriers of 1-3 D4Z4 reduced alleles: experience of the FSHD Italian National Registry. BMJ Open. 2016 Jan 5;6(1):e007798. doi:10.1136/bmjopen-2015-007798. PubMed PMID: 26733561; PubMed Central PMCID: PMC4716236. Link to article on publisher's websiteDOI
10.1136/bmjopen-2015-007798Permanent Link to this Item
http://hdl.handle.net/20.500.14038/36560PubMed ID
26733561Notes
Full author list omitted for brevity. For the full list of authors, see article.
Related Resources
Link to article in PubMedRights
This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:http://creativecommons.org/licenses/by-nc/4.0/
Distribution License
http://creativecommons.org/licenses/by-nc/4.0/ae974a485f413a2113503eed53cd6c53
10.1136/bmjopen-2015-007798
Scopus Count
Collections
Except where otherwise noted, this item's license is described as <p>This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:<a href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</a></p>