An Atypical Case of Progressive Spinal Amyotrophy (Type I) Likely Explained by Genetic Modifiers Case Report

Introduction: Spinal muscular atrophy (SMA) is a group of inherited disorders associated with lower motor neuron depletion. Electromyography and muscle biopsy features of denervation were once the basis for diagnosis, but molecular testing for homozygous deletion or mutation of the SMN1 gene allows for an efficient and specific diagnosis. Although SMN1has been identified as the SMA disease-determining gene, modifier genes mapped to 5q13 were affirmed to play a crucial role in determination of the disease severity and used as a target for SMA therapy. SMN2 copy number and other genetic modifiers in SMA patients can result in aprognosis outside the spectrum of the expected clinical evolutionin patients with homozygous deletion of SMN1.

Case Report: We report the case of a 64-year old patient who, since birth, had been diagnosed with type 1 SMA. However, the patient presented with a slower than expected disease progression for a type 1 SMA patient. Currently, although tetraparetic and functionally limited, the patient is still alive.

Results and Discussion: PCR analysis identified deletion in exons 7 and 8 of the SMN1 gene and confirmed the diagnosis of SMA.

Final Considerations: Our case report provides an overview of the clinical manifestations of SMA, comparing the findings of the neurological examination with the genetic panel. Understanding how genetic modifiers can affect the SMA disease phenol type will contribute to the basic understanding of the disease mechanism and further the development of new treatment strategies; guiding neurologists in diagnosis, prognosis, and treatment.

Keywords:SMA; Genetic; Prognosis; SMN; Motor neuron