SMA is a rare, monogenic, neurodegenerative disorder that is often delayed in its diagnosis1,2
Spinal muscular atrophy (SMA) is the No. 1 genetic cause of death in infants3
SMA is a disease caused by the deletion or mutation of the survival motor neuron 1 (SMN1) gene. It is characterized by a progressive loss of motor neurons, missed motor milestones, and, in its most severe forms, a premature death.2,4
Understanding SMA Type 1
While there are multiple types of SMA, SMA Type 1 is the most common and one of the most severe forms of the disease.4 Although infants with SMA Type 1 may appear normal at birth, weakness can present within the first few months of life as rapid denervation occurs.5,6
In a natural history study, more than 90% of patients with SMA Type 1 did not survive or needed permanent ventilatory support by 2 years of age7
aEvent-free survival for Finkel et al=no death or no need for 16 hours/day ventilation continuously for 2 weeks, in the absence of an acute reversible illness; n=23 (2 copies of SMN2).7
bEvent-free survival for Kolb et al=no death or no tracheostomy; n=20.8
Clinical features of SMA Type 1 include:
Birth to 1 month of age
- Normal birth and possible achievement of early developmental milestones5
2 to 6 months of age
- Muscle weakness and decreased muscle tone, particularly in the lower limbs9
- Hypotonia (ie, floppy baby syndrome)6,10
- Weakness of the diaphragm and intercostal muscles, resulting in paradoxical breathing or “belly breathing”5
- Poor head control5
- Missed motor milestones and regression in motor development10
- Tongue tremors (fasciculations)5
8 to 24 months of age
- Reduced bulbar function, including impaired swallowing and feeding5,10
- Progressive respiratory failure requiring noninvasive ventilation (NIV), bi-level positive airway pressure (BiPAP), or tracheostomy5,7
- Death or permanent ventilatory support7
- As soon as you suspect SMA Type 1, refer your patients for genetic testing
Don’t miss the narrow therapeutic window for SMA Type 1
Because infants with SMA may present with nonspecific symptoms, physicians may often take a “wait and see” approach to diagnosis11
Overlooking early symptoms and prolonging a patient’s diagnostic journey may result in missing a critical window for stopping the progression of SMA Type 1. As the loss of motor neurons is irreversible, early diagnosis and treatment are essential for improving patient outcomes.12
Genetic testing is the gold standard for diagnosing SMA3
In healthy individuals, the SMN1 gene produces full-length, functional SMN protein. However, patients with SMA rely on an SMN1 backup gene, SMN2, which produces only 10% functional SMN protein.4
A genetic test can confirm a homozygous mutation of the SMN1 gene3
SMN2 is considered a prognostic indicator for disease type and severity due to copy number variations. Having fewer copies of SMN2 is correlated with a more severe phenotype.10,13
Additional testing can confirm SMN2 copy number14
Novartis Gene Therapies offers the Novartis Gene Therapies Laboratory Program to facilitate SMA genetic testing and anti-AAV9 antibody testing
Resources for the families and caregivers of patients with SMA
If you have a patient with a presumptive or confirmed SMA diagnosis, these resources may help them understand SMA and navigate the treatment options available to them.
Proper SMA care requires a multidisciplinary care team
In addition to regular well visits with their pediatrician, patients may require respiratory, nutritional, and musculoskeletal support. These fundamental elements of SMA care can help maximize functional ability for those with all types of SMA.14,15
