A study published using data from the SMA France register, set up in 2020, shows a wide variety of phenotypes in patients with SMN1-related proximal spinal muscular atrophy (SMA) with homozygous deletion of the SMN1 gene and four copies of the SMN2 gene, sometimes more severe than expected.
- As of May 2023, 1,112 patients were registered in the SMA France registry.
- Of these, 140 patients (16.1%) carried a homozygous deletion of the SMN1 gene and four copies of the SMN2 gene, including 123 with type III SMA, 12 with type II and five with type IV.
- The median age of onset was 3.5 years and the median follow-up 32 years.
- Symptoms appeared in childhood in most patients, before the age of three in 37.4% of type IIIs, with a progressive course of the disease.
- Two-thirds of patients needed a wheelchair to get around.
- The rates of use of scoliosis surgery and ventilation were less than 15%.
- Problems with chewing and swallowing affected only 10.7% of patients.
- Half the patients needed help at school or a carer for adults.
- The overall phenotype was milder than expected for type II patients.
- A gender effect is suggested by the predominance of males in the cohort (63%) and the more severe progression of the disease in males.
However, further in-depth studies are required, in particular to assess the value of presymptomatic treatment in this population presenting four copies of SMN2 and sometimes a more severe phenotype than expected.
