Abstract
1.64eP The natural history and treatment effects of SMA patients with ≥4 SMN2 copies in the USA
Neuromuscular disorders : NMD, Vol.67(Suppl 1), 106611
10/2026
DOI: 10.1016/j.nmd.2026.106611
Abstract
Spinal muscular atrophy (SMA) is a progressive neurodegenerative condition of the motor neurons that result in paralysis and death in the most severe cases, if untreated. SMA is caused by a homozygous deletion of SMN1 and varying number of copies of a paralog gene called SMN2. A higher SMN2 copy number generally correlates with a milder phenotype, corresponding to the historical subtypes of SMA 1-4. While a robust natural history for 2-3 copies of SMN2 exist, there is a burgeoning body of evidence for the natural history of 4 or more copies of SMN2 outside of the USA. We present the first retrospective natural history of treated and untreated 4 SMN2 copy patients in the USA. 221 subjects were included in the study with a SMN2 copy number breakdown of 169 with 4 SMN2 copies (76%), 42 with 4 or higher copies (19%), 9 with 5 copies (0.04%), 1 with 6 copies. 58.4% were male. The average age of onset of symptoms was 2.85 years in the entire cohort (primarily untreated). Walking was achieved at 1 year in the overall population (n=160) while the median age of loss of ambulation in those that lost this ability without treatment was 13 years (n=31). The age of loss of ambulation at 50% cumulative incidence was 56 years. The most common first symptom (43.9%) was an abnormal walking, running or climbing pattern after having achieved walking normally. Non-invasive ventilation was used in 7.2% (n=16) of subjects. If diagnosis was conferred on newborn screening (NBS), the median age of start of treatment was 0.12 years (n=53) while symptomatic subjects were treated on average at 15.6 years (n=142). 88% of subjects opted to start treatment. With treatment, the overall annual rate of change of HFMSE was 0.27 (p=0.007) and RULM -0.08 (p=0.087). Our data support that 4 copies of SMN2 is a pediatric-onset disease with significant disability if left untreated. Disability ranges from loss of ambulation in a small cohort, wheelchair dependency and even need for non-invasive ventilation. This highlights the importance of capturing the exact copy number on newborn screening and early treatment to prevent motor deterioration later in life.
Details
- Title: Subtitle
- 1.64eP The natural history and treatment effects of SMA patients with ≥4 SMN2 copies in the USA
- Creators
- Chamindra Laverty - University of California San DiegoRandell Richardson - Gillette Children's Specialty HealthcareKuntz Nancy - Ann & Robert H Lurie Children’s Hosp Chicago, USAKaitlin Batley - Univ Texas Southwestern Med Center, Dallas, USASusan Apkon - Children’s Hosp Colorado, Aurora, USAJulie Parsons - Children’s Hosp Colorado, Aurora, USADiana Bharucha-Goebel - Children’s Nat Hosp, Washington D.C., USASarah Wright - Children’s Nat Hosp, Washington D.C., USAKatherine Mathews - University of IowaDimah Saade - University of IowaLeigh Ramos-Platt - Univ Southern California & Children’s Hosp of Los Angeles, USAJulian Thomas - Univ Irvine Med Center & Children’s Hosp of Orange County, Orange, USAEmma Ciafaloni - University of RochesterCuixia Tian - University of CincinnatiOmer Abdul Hamid - Nemours Children’s Hosp, Orlando, USAKapil Arya - Univ Arkansas for Med Sciences, Little Rock, USABakri Elsheikh - The Ohio State UniversityJohn Brandsema - University of PennsylvaniaRussell Butterfield - University of UtahCarolina Tesi-Rocha - Stanford University
- Resource Type
- Abstract
- Publication Details
- Neuromuscular disorders : NMD, Vol.67(Suppl 1), 106611
- DOI
- 10.1016/j.nmd.2026.106611
- ISSN
- 0960-8966
- Publisher
- Elsevier B.V
- Language
- English
- Date published
- 10/2026
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9985240282702771
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