Rianne J M Goselink1, Karlien Mul2, Caroline R van Kernebeek2, Richard J L F Lemmers2, Silvère M van der Maarel2, Tim H A Schreuder2, Corrie E Erasmus2, George W Padberg2, Jeffrey M Statland2, Nicol C Voermans2, Baziel G M van Engelen2. 1. From the Department of Neurology (R.J.M.G., K.M., C.R.v.K., T.H.A.S., C.E.E., G.W.P., N.C.V., B.G.M.v.E.), Donders Center for Neuroscience, Radboud University Medical Center, Nijmegen; Department of Human Genetics (R.J.L.F.L., S.M.v.d.M.), Leiden University Medical Center, the Netherlands; and Department of Neurology (J.M.S.), Kansas University Medical Center, Kansas City. Rianne.Goselink@radboudumc.nl. 2. From the Department of Neurology (R.J.M.G., K.M., C.R.v.K., T.H.A.S., C.E.E., G.W.P., N.C.V., B.G.M.v.E.), Donders Center for Neuroscience, Radboud University Medical Center, Nijmegen; Department of Human Genetics (R.J.L.F.L., S.M.v.d.M.), Leiden University Medical Center, the Netherlands; and Department of Neurology (J.M.S.), Kansas University Medical Center, Kansas City.
Abstract
OBJECTIVE: To assess the relation between age at onset and disease severity in facioscapulohumeral muscular dystrophy (FSHD). METHODS: In this prospective cross-sectional study, we matched adult patients with FSHD with an early disease onset with 2 sex-matched FSHD control groups with a classic onset; the first group was age matched, and the second group was disease duration matched. Genetic characteristics, muscle performance, respiratory functioning, hearing loss, vision loss, epilepsy, educational level, and work status were compared with the 2 control groups. RESULTS: Twenty-eight patients with early-onset FSHD were age (n = 28) or duration (n = 27) matched with classic-onset patients. Patients with early-onset FSHD had more severe muscle weakness (mean FSHD clinical score 11 vs 5 in the age-matched and 9 in the duration-matched group, p < 0.05) and a higher frequency of wheelchair dependency (57%, 0%, and 30%, respectively, p < 0.05). In addition, systemic features were more frequent in early-onset FSHD, most important, hearing loss, decreased respiratory function and spinal deformities. There was no difference in work status. Genetically, the shortest D4Z4 repeat arrays (2-3 units) were found exclusively in the early-onset group, and the largest repeat arrays (8-9 units) were found only in the classic-onset groups. De novo mutations were more frequent in early-onset patients (46% vs 4%). CONCLUSIONS: Patients with early-onset FSHD more often have severe muscle weakness and systemic features. The disease severity is greater than in patients with classic-onset FSHD who are matched for disease duration, suggesting that the progression is faster in early-onset patients.
OBJECTIVE: To assess the relation between age at onset and disease severity in facioscapulohumeral muscular dystrophy (FSHD). METHODS: In this prospective cross-sectional study, we matched adult patients with FSHD with an early disease onset with 2 sex-matched FSHD control groups with a classic onset; the first group was age matched, and the second group was disease duration matched. Genetic characteristics, muscle performance, respiratory functioning, hearing loss, vision loss, epilepsy, educational level, and work status were compared with the 2 control groups. RESULTS: Twenty-eight patients with early-onset FSHD were age (n = 28) or duration (n = 27) matched with classic-onset patients. Patients with early-onset FSHD had more severe muscle weakness (mean FSHD clinical score 11 vs 5 in the age-matched and 9 in the duration-matched group, p < 0.05) and a higher frequency of wheelchair dependency (57%, 0%, and 30%, respectively, p < 0.05). In addition, systemic features were more frequent in early-onset FSHD, most important, hearing loss, decreased respiratory function and spinal deformities. There was no difference in work status. Genetically, the shortest D4Z4 repeat arrays (2-3 units) were found exclusively in the early-onset group, and the largest repeat arrays (8-9 units) were found only in the classic-onset groups. De novo mutations were more frequent in early-onset patients (46% vs 4%). CONCLUSIONS:Patients with early-onset FSHD more often have severe muscle weakness and systemic features. The disease severity is greater than in patients with classic-onset FSHD who are matched for disease duration, suggesting that the progression is faster in early-onset patients.
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Authors: Richard J L F Lemmers; Patrick J van der Vliet; Ana Blatnik; Judit Balog; Janez Zidar; Don Henderson; Rianne Goselink; Stephen J Tapscott; Nicol C Voermans; Rabi Tawil; George W A M Padberg; Baziel Gm van Engelen; Silvère M van der Maarel Journal: J Med Genet Date: 2021-01-12 Impact factor: 6.318
Authors: Sanne C C Vincenten; Nienke Van Der Stoep; Aimée D C Paulussen; Karlien Mul; Umesh A Badrising; Marjolein Kriek; Olivier W H Van Der Heijden; Baziel G M Van Engelen; Nicol C Voermans; Christine E M De Die-Smulders; Saskia Lassche Journal: Clin Genet Date: 2021-08-01 Impact factor: 4.296