BACKGROUND: Spinal muscular atrophy (SMA) is caused by a homozygous deletion of the survival motor neuron (SMN)1 gene. The nearly identical SMN2 gene plays a disease modifying role. SMA is classified into four different subtypes based on age of onset and clinical course (SMA types 1-4). The natural history of early onset SMA types 1-3a has been studied extensively. Late onset SMA is rare and disease course has not been studied in detail. OBJECTIVE: To perform a prospective study on the clinical course and the correlation with SMN2 copy numbers of late onset SMA. METHODS: Patients fulfilling the diagnostic criteria for late onset SMA (types 3b and 4) were included in the study. At inclusion and follow-up, muscle strength, respiratory function, functional status and quality of life were assessed. SMN2 copy number was determined in all patients. RESULTS: Twelve patients were identified and included. Six patients were siblings from one family, two patients were brothers from a second family and four patients were sporadic cases. All patients carried four copies of the SMN2 gene. Median age of disease onset was 22.2 years (10-37). Age of disease onset in patients from family one was lower as compared to the other patients. None of the outcome measures changed after a follow-up of 2.5 years. Five patients reported an increase in fatigue and muscle weakness. None of the patients showed symptoms of respiratory insufficiency. CONCLUSIONS: This study indicates that late onset SMA is not characterized by disease progression and that alternative or surrogate disease markers are required for the design of future trials. This study confirms the finding that SMN2 copy number is a SMA disease course modifier.
BACKGROUND:Spinal muscular atrophy (SMA) is caused by a homozygous deletion of the survival motor neuron (SMN)1 gene. The nearly identical SMN2 gene plays a disease modifying role. SMA is classified into four different subtypes based on age of onset and clinical course (SMA types 1-4). The natural history of early onset SMA types 1-3a has been studied extensively. Late onset SMA is rare and disease course has not been studied in detail. OBJECTIVE: To perform a prospective study on the clinical course and the correlation with SMN2 copy numbers of late onset SMA. METHODS:Patients fulfilling the diagnostic criteria for late onset SMA (types 3b and 4) were included in the study. At inclusion and follow-up, muscle strength, respiratory function, functional status and quality of life were assessed. SMN2 copy number was determined in all patients. RESULTS: Twelve patients were identified and included. Six patients were siblings from one family, two patients were brothers from a second family and four patients were sporadic cases. All patients carried four copies of the SMN2 gene. Median age of disease onset was 22.2 years (10-37). Age of disease onset in patients from family one was lower as compared to the other patients. None of the outcome measures changed after a follow-up of 2.5 years. Five patients reported an increase in fatigue and muscle weakness. None of the patients showed symptoms of respiratory insufficiency. CONCLUSIONS: This study indicates that late onset SMA is not characterized by disease progression and that alternative or surrogate disease markers are required for the design of future trials. This study confirms the finding that SMN2 copy number is a SMA disease course modifier.
Authors: Jessica M O'Hagen; Allan M Glanzman; Michael P McDermott; Patricia A Ryan; Jean Flickinger; Janet Quigley; Susan Riley; Erica Sanborn; Carrie Irvine; William B Martens; Christine Annis; Rabi Tawil; Maryam Oskoui; Basil T Darras; Richard S Finkel; Darryl C De Vivo Journal: Neuromuscul Disord Date: 2007-07-19 Impact factor: 4.296
Authors: K Zerres; S Rudnik-Schöneborn; E Forrest; A Lusakowska; J Borkowska; I Hausmanowa-Petrusewicz Journal: J Neurol Sci Date: 1997-02-27 Impact factor: 3.181
Authors: P E McAndrew; D W Parsons; L R Simard; C Rochette; P N Ray; J R Mendell; T W Prior; A H Burghes Journal: Am J Hum Genet Date: 1997-06 Impact factor: 11.025
Authors: Markus Feldkötter; Verena Schwarzer; Radu Wirth; Thomas F Wienker; Brunhilde Wirth Journal: Am J Hum Genet Date: 2001-12-21 Impact factor: 11.025
Authors: M Gennarelli; M Lucarelli; F Capon; A Pizzuti; L Merlini; C Angelini; G Novelli; B Dallapiccola Journal: Biochem Biophys Res Commun Date: 1995-08-04 Impact factor: 3.575
Authors: Renske I Wadman; W Ludo van der Pol; Wendy Mj Bosboom; Fay-Lynn Asselman; Leonard H van den Berg; Susan T Iannaccone; Alexander Fje Vrancken Journal: Cochrane Database Syst Rev Date: 2020-01-06
Authors: J Montes; M P McDermott; W B Martens; S Dunaway; A M Glanzman; S Riley; J Quigley; M J Montgomery; D Sproule; R Tawil; W K Chung; B T Darras; D C De Vivo; P Kaufmann; R S Finkel Journal: Neurology Date: 2010-03-09 Impact factor: 9.910