Spectrum of SMA Phenotypes at Presentation

Tim Hagenacker, MD: The current classification includes 4 phenotypes with a large heterogeneity of the symptoms of the disease. On 1 end of the spectrum, we have the more severely affected infants. Those are SMA [spinal muscular atrophy] type 1 patients with a heavy involvement of ventilation of the phrenic-innervated muscles. On the other end of the spectrum, we have patients with SMA types 3 or 4, with a minor involvement of the muscles of the extremities. Especially in the SMA type 3 population, there is a large heterogeneity. We have patients who lose their status of ambulation within their first years of life, and on the other hand, we have some patients who are still able to walk in their 40s, so there is a large heterogeneity.

Within the last several years, we doubt the existence of an SMA type 4. When you ask these SMA type 4 patients, who you may think only had involvement after reaching adulthood, you can see that there are always minor symptoms within their adolescent years. The patients who are now classified as SMA type 4 have minor forms of SMA type 3.

The spectrum of the disease is largely heterogeneous in severity. A severely impaired patient with early problems who needs mechanical ventilation within their first years of life is on 1 end. On the other end of the spectrum are patients with only minor involvement of extremities who have minor problems when climbing stairs or performing activities like that. That is the spectrum of the disease.