Population screening for spinal muscular atrophy : a mixed methods study of the views of affected families

Autosomal recessive conditions are a significant health burden with few treatments. Population carrier screening has been suggested as a means to tackle them. Little is known about the views of affected families despite the potential for direct impacts on them. Data are presented on attitudes among families affected by Spinal Muscular Atrophy (SMA) toward two population screening programs, pre-conception, and prenatal. Data were gathered through qualitative interviews (n = 36) and a survey (n = 337). Eighty-two survey participants had SMA and 255 were family members. The majority were in favor of screening (75%). Reasons for supporting pre-conception screening support were a belief that it would reduce SMA-related terminations and raise awareness of SMA in the population. For prenatal screening, reasons for support included a belief in the importance of informed decision-making and the need to reduce suffering. Key reasons for non-support of pre-conception screening included concerns about carrier stigmatization and social engineering. For prenatal screening, concerns focused on the collateral loss of high quality of life lives affected by SMA. This study highlights that those affected by SMA are predominantly in favor of screening, although pre-conception screening is most favored. While family members and adults with SMA had largely consistent views, perceptions varied according to the severity (type) of SMA, with those affected by SMA type II the least likely to support screening. These findings suggest that screening for SMA is a complex issue for affected families, underscoring the need to consider and include their views when planning and implementing screening programs. © 2016 Wiley Periodicals, Inc

Newborn screening for spinal muscular atrophy : the views of affected families and adults

Spinal muscular atrophy (SMA) is one of the leading genetic causes of infant death worldwide. However, due to a lack of treatments, SMA has historically fallen short of Wilson-Jungner criteria. While studies have explored the acceptability of expanded newborn screening to the general public, the views of affected families have largely been overlooked. This is in spite of the potential for direct impacts on them and their unique positioning to consider the value of early diagnosis. We have previously reported data on attitudes towards pre-conception and prenatal genetic screening for SMA amongst affected families (adults with SMA (n=82) and family members (n=255)). Here, using qualitative interview (n= 36) and survey data (n= 337), we report the views of this same cohort towards newborn screening. The majority (70%) of participants were in favour, however, all sub-groups (except adults with type II) preferred pre-conception and/or prenatal screening to newborn screening. Key reasons for newborn screening support were: 1) the potential for improved support 2) the possibility of enrolling pre-symptomatic children on clinical trials. Key reasons for non-support were: 1) concerns about impact on the early experiences of the family 2) inability to treat. Importantly, participants did not view the potential for inaccurate typing as a significant obstacle to the launch of a population-wide screening programme. This study underscores the need to include families affected by genetic diseases within consultations on screening. This is particularly important for conditions such as SMA which challenge traditional screening criteria, and for which new therapeutics are emerging

The role of experiential knowledge within attitudes towards genetic carrier screening : a comparison of people with and without experience of spinal muscular atrophy

Purpose: Autosomal recessive conditions, whilst individually rare, are a significant health burden with limited treatment options. Population carrier screening has been suggested as a means of tackling them. Little is known, however, about the attitudes of the general public towards such carrier screening and still less about the views of people living with candidate genetic diseases. Here, we focus on the role that such experience has on screening attitudes by comparing the views of people with and without prior experience of the monogenetic disorder, Spinal Muscular Atrophy. Methods: An exploratory sequential mixed methods design was adopted. In-depth qualitative interviews were used to develop two surveys. The surveys addressed attitudes towards carrier screening (pre-conceptual and prenatal) for SMA. Participants: 337 participants with SMA experience completed the SMA Screening Survey (UK) and 336 participants with no prior experience of SMA completed the UK GenPop Survey, an amended version of the SMA Screening Survey (UK). Results: The majority of both cohorts were in favour of pre-conception and prenatal carrier screening, however people with experience of type II SMA were least likely to support either. Key differences emerged around perceptions of SMA, with those without SMA experience taking a dimmer than those with

Onasemnogene abeparvovec preserves bulbar function in infants with presymptomatic spinal muscular atrophy: a post-hoc analysis of the SPR1NT trial

Bulbar function in spinal muscular atrophy has been defined as the ability to meet nutritional needs by mouth while maintaining airway protection and communicate verbally. The effects of disease-modifying treatment on bulbar function are not clear. A multidisciplinary team conducted post-hoc analyses of phase 3 SPR1NT trial data to evaluate bulbar function of infants at risk for spinal muscular atrophy who received one-time gene replacement therapy (onasemnogene abeparvovec) before symptom onset. Three endpoints represented adequate bulbar function in SPR1NT: (1) absence of physiologic swallowing impairment, (2) full oral nutrition, and (3) absence of adverse events indicating pulmonary instability. Communication was not assessed in SPR1NT. We descriptively assessed numbers/percentages of children who achieved each endpoint and all three collectively. SPR1NT included infants <6 postnatal weeks with two (n = 14) or three (n = 15) copies of the survival motor neuron 2 gene. At study end (18 [two-copy cohort] or 24 [three-copy cohort] months of age), 100% (29/29) of patients swallowed normally, achieved full oral nutrition, maintained pulmonary stability, and achieved the composite endpoint. When administered to infants before clinical symptom onset, onasemnogene abeparvovec allowed children at risk for spinal muscular atrophy to achieve milestones within published normal ranges of development and preserve bulbar function

Genetic therapies for inherited neuromuscular disorders

Inherited neuromuscular disorders encompass a broad group of genetic conditions, and the discovery of these underlying genes has expanded greatly in the past three decades. The discovery of such genes has enabled more precise diagnosis of these disorders and the development of specific therapeutic approaches that target the genetic basis and pathophysiological pathways. Such translational research has led to the approval of two genetic therapies by the US Food and Drug Administration: eteplirsen for Duchenne muscular dystrophy and nusinersen for spinal muscular atrophy, which are both antisense oligonucleotides that modify pre-mRNA splicing. In this Review we aim to discuss new genetic therapies and ongoing clinical trials for Duchenne muscular dystrophy, spinal muscular atrophy, and other less common childhood neuromuscular disorders

Impairment experiences, identity and attitudes towards genetic screening : the views of people with Spinal Muscular Atrophy

Developments in genetics are rapidly changing the capacity and scope of screening practices. However, people with genetic conditions have been under-represented in the literature exploring their implications. This mixed methods study explores the attitudes of people with Spinal Muscular Atrophy (SMA) towards three different population-level genetic screening programmes for SMA: pre-conception, prenatal and newborn. Drawing on qualitative interviews (n= 15) and a survey (n=82), this study demonstrates that more severely affected individuals with early-onset symptoms (Type II SMA), are less likely to support screening and more likely to view SMA positively than those with milder, later onset and/or fluctuating symptoms (Types III/ IV SMA). Indeed, this clinically milder group were more likely to support all forms of screening and view SMA negatively. This paper highlights that screening is a complex issue for people with genetic conditions, and the nature of impairment experiences plays a critical role in shaping attitudes

Fatigue in Children and Adolescents with Duchenne Muscular Dystrophy

Fatigue was recently reported to be the largest predictor of poor health-related quality of life (HRQOL) in children and adolescents with Duchenne muscular dystrophy (DMD). The objectives of this thesis were to describe fatigue from patients’ and parents’ perspectives and to explore associations of patient characteristics with fatigue in children and adolescents with DMD using a multicentre cross-sectional study design. Eligible patients and their parents were identified via the Canadian Neuromuscular Disease Registry and received mailed paper questionnaires. Children and adolescents with DMD experienced greater fatigue compared to healthy controls from published data. Fatigue was a significant issue in children and adolescents with DMD across all disease stages. Sleep disturbance symptoms, depressive symptoms and functional ability were associated with fatigue. Physical activity level was not associated with fatigue. These findings warrant future research aimed at understanding the determinants of fatigue and developing therapeutic strategies to reduce fatigue and improve HRQOL

Quality of Life and Health-Related Quality of Life in Children with Duchenne Muscular Dystrophy

Quality of life studies in Duchenne Muscular Dystrophy are scarce. This study explores the relationship between the broad concept of quality of life and the more focused concept of health-related quality of life and examines the relationships between patient and family characteristics and health-related quality of life. Participants were recruited from the Canadian Neuromuscular Disease Registry, 98 parents and 85 children completed the Quality of My Life and Pediatric Quality of Life Inventory questionnaires. Simple regression was used to examine the relationship between quality of life and health-related quality of life. Multivariable linear regressions were used to determine child and family characteristics associated with health-related quality of life outcomes. Higher levels of subjective fatigue and use of wheelchair emerged as factors most consistently associated with lower levels health-related quality of life. Interventions to reduce fatigue could lead to improvement of health-related quality of life for children with Duchenne Muscular Dystrophy

Psychological and care impact of the daily use of a pediatric gait exoskeleton in children with spinal muscular atrophy

Introducción: La Atrofia Muscular Espinal Tipo II, es una enfermedad neurodegenerativa de origen genético que cursa con debilidad muscular y provoca deterioro motor e incapacidad para caminar en los niños. Se relaciona con graves problemas respiratorios, musculoesqueléticos, gastrointestinales y otros de salud y cuidado. Los exoesqueletos robóticos de miembros inferiores son dispositivos médicos que ayudan a la marcha de pacientes que no pueden caminar. Nuestro objetivo fue evaluar el impacto en la dimensión psicológica y de autocuidado derivado del uso del exoesqueleto ATLAS en el hogar en niños con Atrofia Muscular Espinal Tipo II. Metodología: tres niños con Atrofia Muscular Espinal Tipo II utilizaron el exoesqueleto en casa cinco días a la semana durante un período de dos meses para caminar y realizar actividades. Se realizó una evaluación del autocuidado de enfermería antes y durante el uso del dispositivo para evaluar los cambios en los resultados del autocuidado y los diagnósticos de enfermería. Se realizaron entrevistas en profundidad y semiestructuradas, además de la observación durante las sesiones, para evaluar el impacto de la experiencia en la dimensión psicológica de los participantes. Resultados: el uso del exoesqueleto produjo cambios en los condicionantes básicos de los niños y una mejora en los organismos de autocuidado. También aparecieron nuevas demandas de autocuidado. Tres de los diez diagnósticos de enfermería fueron resueltos. Asimismo, los niños mostraron una buena tolerancia a la actividad además de una mejora funcional evaluada en el tercer participante. Los niños y los cuidadores principales valoraron la experiencia como positiva y significativa. Los niños tenían una mayoría de emociones positivas, y se incrementó su autonomía y comportamiento social y exploratorio. Conclusiones: la tecnología del exoesqueleto podría considerarse como un nuevo recurso para el cuidado de niños con enfermedades neuromusculares. Su uso tuvo un impacto positivo tanto en las variables de autocuidado como en la dimensión psicológica de tres niños con atrofia muscular espinal tipo II. Aunque este estudio aporta ya evidencia, más estudios sobre el tema aportarían un mayor conocimiento