Newborn and Carrier Screening for Spinal Muscular Atrophy

Prior, Thomas W.; Snyder, Pamela J.; Rink, B; Pearl, Dennis K.; Pyatt, Robert E.; Mihal, David; Conlan, Todd; Schmalz, Betsy; Montgomery, Laura; Ziegler, Katie L. Allen; Noonan, Carolee; Hashimoto, Sayaka; Garner, Shannon

doi:10.1097/ogx.0b013e318202208f

Cited by 30 publications

(60 citation statements)

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“…[28][29][30] Similarly, SMA could be considered for inclusion. 7 When presented with screening options, such as screening children in the newborn or infant period, participants in our study highlighted the complexity of choosing an appropriate time to test, because of the variability in the phenotype between SMA types and even within the same SMA type. If screening were to be implemented, it is likely that testing would involve mutation analysis thereby identifying every type of SMA, including late childhood and adult-onset types, rather than screening based on biochemical markers or clinical features.…”

Section: Description Of Participantsmentioning

confidence: 95%

“…One pilot study in the USA addressed the clinical acceptability of carrier screening for SMA in the general population, finding that 60% of women seeking prenatal genetic counselling services accepted SMA carrier testing at the time of counselling. 7 About 75% of women had not heard of SMA previously and all received pre-test genetic counselling, although their decision-making processes and their views about screening at different life stages were not explored. 7 FXS and cystic fibrosis studies consistently show a preference for carrier screening over other screening options, with this occurring ideally before pregnancy.…”

Section: Description Of Participantsmentioning

confidence: 99%

“…7 About 75% of women had not heard of SMA previously and all received pre-test genetic counselling, although their decision-making processes and their views about screening at different life stages were not explored. 7 FXS and cystic fibrosis studies consistently show a preference for carrier screening over other screening options, with this occurring ideally before pregnancy. [31][32][33] Increasingly, carrier screening for panels of genetic conditions are being offered 34 and a carrier screening program combining testing for SMA, FXS and cystic fibrosis has recently been launched in Victoria, Australia; uptake of testing has not yet been determined.…”

Section: Description Of Participantsmentioning

confidence: 99%

“…SMA is an autosomal recessive neuromuscular disease with a carrier frequency of 1 in 41 reported in the Australian population 5 and an estimated incidence of 1 in 6000 to 1 in 10 000 live births internationally. 6,7 Degeneration of motor neurons in the spine and lower brainstem lead to muscle weakness and atrophy. 8 This degeneration has been shown to be due to homozygous defects of the spinal motor neuron gene, SMN1.…”

Section: Introductionmentioning

confidence: 99%

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A mixed methods exploration of families’ experiences of the diagnosis of childhood spinal muscular atrophy

et al. 2014

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Section: Description Of Participantsmentioning

confidence: 95%

Section: Description Of Participantsmentioning

confidence: 99%

Section: Description Of Participantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A mixed methods exploration of families’ experiences of the diagnosis of childhood spinal muscular atrophy

et al. 2014

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“…In US Whites, B1 in 35 are SMA carriers. 1,2 SMA is caused by the homozygous loss of survival motor neuron 1 (SMN1) gene function due to a deletion or possibly to a gene conversion event in B95% of cases; 3 the remaining 5% of patients have intragenic mutations that inactivate the gene. [4][5][6] Affected individuals exhibit progressive muscle weakness and paralysis as a result of degeneration and loss of motor neurons in the spinal cord.…”

Section: Introductionmentioning

confidence: 99%

A common spinal muscular atrophy deletion mutation is present on a single founder haplotype in the US Hutterites

et al. 2011

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Spinal muscular atrophy (SMA) is an autosomal recessive (AR) neuromuscular disease that is one of the most common lethal genetic disorders in children, with carrier frequencies as high as B1 in 35 in US Whites. As part of our genetic studies in the Hutterites from South Dakota, we identified a large 22 Mb run of homozygosity, spanning the SMA locus in an affected child, of which 10 Mb was also homozygous in three affected Hutterites from Montana, supporting a single founder origin for the mutation. We developed a haplotype-based method for identifying carriers of the SMN1 deletion that leveraged existing genome-wide SNP genotype data for B1400 Hutterites. In combination with two direct PCR-based assays, we identified 176 carriers of the SMN1 deletion, one asymptomatic homozygous adult and three carriers of a de novo deletion. This corresponds to a carrier frequency of one in eight (12.5%) in the South Dakota Hutterites, representing the highest carrier frequency reported to date for SMA and for an AR disease in the Hutterite population. Lastly, we show that 26 SNPs can be used to predict SMA carrier status in the Hutterites, with 99.86% specificity and 99.71% sensitivity.

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Maximizing the Benefit of Life-Saving Treatments for Pompe Disease, Spinal Muscular Atrophy, and Duchenne Muscular Dystrophy Through Newborn Screening

et al. 2019

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ewborn screening (NBS) allows for earliest possible diagnosis and intervention for congenital diseases. For neuromuscular diseases (NMDs) such as Pompe disease, spinal muscular atrophy (SMA), and Duchenne muscular dystrophy (DMD), early diagnosis and initiation of treatment in the presymptomatic phase improves clinical outcomes. 1,2 Newborn screening was introduced in the early 1960s as a public health program in the United States and has expanded around the world. 3,4 The diseases screened and the screening processes vary from country to country. 3,4 In the United States, the list of screened diseases is made at the state level, based on the US Department of Health and Human Services-endorsed Recommended Uniform Screening Panel (RUSP). 5 However, diseases may be added to a state panel independent of RUSP approval. 6 Newborn screening programs in Europe are heterogenous, with no consensus on included conditions. 7,8 Many developing countries do not yet have organized NBS processes and have faced challenges in implementing NBS owing to economic and cultural barriers. 4 In this article, we will discuss challenges to implementing NBS for NMDs in the United States and how overcoming those challenges can maximize the potential of newly available life-saving therapies. DiscussionNewborn Screening: The US Experience Conditions to be included on the RUSP are recommended to the US Department of Health and Human Services by the Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC), 6,9 created by the US Congress to promote a uniform national NBS panel of diseases that meet evidence-based requirements (Box). 6,[9][10][11] The RUSP list includes 35 core and 26 secondary conditions. 6,10 During the review process, the committee considers the evidence of a reliable confirmatory diagnostic test, approved effective treatment, and how early intervention can reduce morbidity. Additionally, cost-effectiveness analysis and public health readiness are evaluated prior to addition of a condition to the RUSP but do not preclude the addition of a condition to the panel. 12 IMPORTANCE Newborn screening (NBS) identifies infants with specific congenital disorders for which earlier intervention cannot only prevent a lifetime of chronic disability but also, most importantly, save lives. In this article, we discuss complexities associated with NBS processes in the United States, with a focus on challenges in neuromuscular disorders.OBSERVATIONS As new interventions for neuromuscular disorders become available, the clinical community must prepare to overcome the challenges of adding new diseases to screening panels and understand the rigorous evidence review at the federal level and the complex process of state-level implementation. In this regard, NBS programs for Pompe disease and spinal muscular atrophy can guide the path of Duchenne muscular dystrophy and other neuromuscular disorders as future candidates for NBS. CONCLUSIONS AND RELEVANCEThe availability of advanced screening methods, the emergence of effective treatm...

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Newborn and Carrier Screening for Spinal Muscular Atrophy

Cited by 30 publications

References 0 publications

A mixed methods exploration of families’ experiences of the diagnosis of childhood spinal muscular atrophy

A mixed methods exploration of families’ experiences of the diagnosis of childhood spinal muscular atrophy

A common spinal muscular atrophy deletion mutation is present on a single founder haplotype in the US Hutterites

Maximizing the Benefit of Life-Saving Treatments for Pompe Disease, Spinal Muscular Atrophy, and Duchenne Muscular Dystrophy Through Newborn Screening

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