Association of motor milestones, SMN2 copy and outcome in spinal muscular atrophy types 0–4

Wadman, Renske I.; Stam, Marloes; Gijzen, Marleen; Lemmink, Henny H.; Snoeck, I.; Wijngaarde, Camiel A.; Braun, Kees P.J.; Schoenmakers, Marieke; Berg, Leonard H van den; Dooijes, Dennis; Pol, W‐Ludo van der

doi:10.1136/jnnp-2016-314292

Cited by 102 publications

(118 citation statements)

References 5 publications

(6 reference statements)

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“…We describe transformations in optimal multidisciplinary care accompanying active therapy and increased complexity of clinical decision making. As may be expected, patients diagnosed with SMA prior to initiation of the EAP were older and had the less severe SMA subtype 1c, in which some may survive into childhood 17. This group had already developed clinically significant bulbar and respiratory dysfunction, prompting initiation of enteral feeds and nocturnal non-invasive ventilation, on average at age 6.4 and 9.2 years, respectively.…”

Section: Discussionmentioning

confidence: 57%

Nusinersen for SMA: expanded access programme

Farrar

Teoh

Carey

et al. 2018

J Neurol Neurosurg Psychiatry

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Section: Discussionmentioning

confidence: 57%

Nusinersen for SMA: expanded access programme

Farrar

Teoh

Carey

et al. 2018

J Neurol Neurosurg Psychiatry

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“…Patients enrolled in this study are participating in our ongoing prospective population-based prevalence cohort study on SMA in The Netherlands [18,19]. The study was approved by the local Medical Ethics Committee (No.…”

Section: Design and Participantsmentioning

confidence: 99%

“…In case of discrepancies, acquired motor milestones determined final classification. We used previously published additions to also distinguish subtypes (e.g., 2a-b, 3a-b; Table 1) [2,3,18,19,21]. This is of importance, as a relationship between best acquired motor function and lung function has been reported in several NMDs, including SMA [22].…”

Section: Design and Participantsmentioning

confidence: 99%

“…We retrieved lung function data from prospectively enrolled patients from two sources. First, we used spirometry data (FEV 1 and FVC) obtained from patients in our ongoing study [18], using a handheld calibrated spirometer (MicroLab 3500®, PT Medical). These data were obtained prospectively between March 2013 and June 2018, at every study visit.…”

Section: Lung Function Tests (Lfts)mentioning

confidence: 99%

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Natural history of lung function in spinal muscular atrophy

Wijngaarde

Veldhoen

Eijk

et al. 2020

Orphanet J Rare Dis

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Background: Respiratory muscle weakness is an important feature of spinal muscular atrophy (SMA). Progressive lung function decline is the most important cause of mortality and morbidity in patients. The natural history of lung function in SMA has, however, not been studied in much detail. Results: We analysed 2098 measurements of lung function from 170 treatment-naïve patients with SMA types 1c-4, aged 4-74 years. All patients are participating in an ongoing population-based prevalence cohort study. We measured Forced Expiratory Volume in 1 s (FEV 1), Forced Vital Capacity (FVC), and Vital Capacity (VC). Longitudinal patterns of lung function were analysed using linear mixed-effects and non-linear models. Additionally, we also assessed postural effects on results of FEV 1 and FVC tests. In early-onset SMA types (1c-3a), we observed a progressive decline of lung function at younger ages with relative stabilisation during adulthood. Estimated baseline values were significantly lower in more severely affected patients: %FEV 1 ranged from 42% in SMA type 1c to 100% in type 3b, %FVC 50 to 109%, and %VC 44 to 96%. Average annual decline rates also differed significantly between SMA types, ranging from − 0.1% to − 1.4% for FEV 1 , − 0.2% to − 1.4% for FVC, and + 0.2% to − 1.7% for VC. In contrast to SMA types 1c-3a, we found normal values for all outcomes in later-onset SMA types 3b and 4 throughout life, although with some exceptions and based on limited available data. Finally, we found no important differences in FVC or FEV 1 values measured in either sitting or supine position. Conclusions: Our data illustrate the longitudinal course of lung function in patients with SMA, which is characterised by a progressive decline in childhood and stabilisation in early adulthood. The data do not support an additional benefit of measuring FEV 1 or FVC in both sitting and supine position. These data may serve as a reference to assess longer-term outcomes in clinical trials.

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“…Indeed, SMN2 copy number has been described by some researchers as being linked to disease severity in the majority of cases (with higher numbers of SMN2 copies being associated with milder pathology), although this approach has been somewhat controversial, and criticized for being overly simplistic without consideration of potential gene modifiers (Oprea et al, 2008). In practice, therefore genoand phenotype data are taken into consideration when a symptomatic child is diagnosed with SMA (Gavrilov, Shi, Das, Gilliam, & Wang, 1998;Wadman et al, 2017;Wirth et al, 2006).…”

Section: Spinal Muscular Atrophy and Newborn Genetic Screeningmentioning

confidence: 99%

Newborn genetic screening for spinal muscular atrophy in the UK: The views of the general population

Boardman

Sadler

Young

2017

Molec Gen & Gen Med

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BackgroundSpinal muscular atrophy (SMA) is an inherited neuromuscular disorder and a leading genetic cause of infant death worldwide. However, there is no routine screening program for SMA in the UK. Lack of treatments and the inability of screening tests to accurately predict disease severity are among the key reasons implementation of screening has faltered in the UK. With the recent release of the first therapy for SMA (Nusinersen), calls are being made for a reconsideration of this stance; however, very little is known about the views of the general public.MethodsAn online survey was administered to 232 individuals with no prior relationship with SMA to assess their attitudes toward a newborn screening program for it. Results are compared with previously gathered data on the views of SMA‐affected families toward screening.ResultsEighty‐four percent of participants were in favor of newborn screening. Key reasons for support were a belief that it would lead to better healthcare and life expectancy for affected infants and facilitate informed decision‐making for future pregnancies. Key reasons for nonsupport were a belief in the potential for significant negative impact on the family unit in terms of bonding and stress.ConclusionsPublic acceptability is a key component in the evaluation of any potential screening program in the UK. This study demonstrates that newborn screening for SMA is viewed largely positively by people unfamiliar with the condition. The importance of early identification overrode all other social and ethical concerns about screening for the majority of participants.

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Association of motor milestones, SMN2 copy and outcome in spinal muscular atrophy types 0–4

Cited by 102 publications

References 5 publications

Nusinersen for SMA: expanded access programme

Nusinersen for SMA: expanded access programme

Natural history of lung function in spinal muscular atrophy

Newborn genetic screening for spinal muscular atrophy in the UK: The views of the general population

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