2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Beyond <em>SMN1</em>: review of genotype-phenotype correlation in individuals with >=4 <em>SMN2</em> copy numbers

Pdf Summary

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by the loss of SMN1. Quantifying SMN2 copy number is important for understanding the disease and guiding treatment. However, there is limited data on patients with ≥4 copies of SMN2. The authors conducted a literature review to gather genetic testing results and treatment guidelines for individuals with ≥4 SMN2 copies.<br /><br />The study reviewed data from 301 individuals with ≥4 SMN2 copies. The distribution of SMN2 copy numbers showed that 91.4% had 4 copies, 2.7% had 5 copies, 5.6% had 6 copies, and 0.3% had 8 copies. The distribution of SMA types in these individuals included unaffected (6%), Type I (20%), Type II (4%), Type III (69%), Type IV (1%), and unspecified (0%).<br /><br />The literature review revealed different treatment approaches for individuals with ≥4 SMN2 copies. Some studies treated patients with ≥5 copies as unaffected, while others recommended retesting without further guidance. Intrafamilial variability in SMA phenotype was also observed.<br /><br />The authors concluded that there was no consistent evidence supporting the belief that greater SMN2 copy number is associated with a milder phenotype of SMA. As a result, the practice of excluding patients with ≥4 SMN2 copies from treatment is unsubstantiated and may leave some symptomatic individuals untreated. Further studies on the natural history of individuals with ≥4 SMN2 copies are needed to establish effective treatment plans and predict disease progression.<br /><br />In summary, the review of genetic testing results and treatment guidelines for individuals with ≥4 SMN2 copies in SMA did not consistently support the idea that higher SMN2 copy numbers are linked to milder disease. Excluding these patients from treatment may not be justified, and further research is needed to better understand the disease and guide treatment decisions.

Asset Subtitle

Co-Author - Zoe Powis, Master’s Degree – Genetic Counseling; Co-Author - Meagan Nashawaty, MS, CGC; Presenting Author - Andrea Paal, MS, CGC; Co-Author - Khalida Liaquat, CGC, LGC, MSGC;

Meta Tag

Clinical Applications of Molecular Cytogenetics

Genetic Testing

Genotype-Phenotype Correlations

Co-Author Zoe Powis, Master’s Degree – Genetic Counseling

Co-Author Meagan Nashawaty, MS, CGC

Co-Author Khalida Liaquat, CGC, LGC, MSGC

Presenting Author Andrea Paal, MS, CGC

Keywords

Spinal muscular atrophy

neuromuscular disorder

SMN1 loss

SMN2 copy number

genetic testing

treatment guidelines

distribution of SMN2 copy numbers

SMA types

treatment approaches

intrafamilial variability