Clinical Aspects of SMA Flashcards
Describe Spinal Muscular Atrophy (SMA).
- SMA is a variable condition.
- It leads to symmetrical proximal muscle weakness due to progressive degeneration and loss of the anterior horn cells.
- Onset of weakness ranges from birth to adolescence.
- Although there is a continuum of severity the condition is often divided into 3 types.
- Facial expression and intelligence are normal.
- Early childhood prevalence is 1 in 10,000.
What is the early childhood prevalence of SMA?
Early childhood prevalence is 1 in 10,000.
SMA is due to the loss of which type of cells?
SMA leads to symmetrical proximal muscle weakness due to progressive degeneration and loss of the anterior horn cells - due to missing a gene that helps these cells survive.
Describe the 3 types of SMA.
These are clinical classifications that were devised before the genetics of the condition were understood.
1). Type I SMA (Werdnig-Hoffman):
Severe muscle weakness with absence of movement and hypotonia in the first few months of life. Frog-like posture. There are absent deep tendon reflexes, fasciculation and there may be mild contractures. Fatal respiratory failure usually occurs by age 2 years and often before 6 months. Decreased foetal movements are common.
2). Type II (intermediate form):
Onset before 18 months. Ability to sit but not walk unaided. Can survive into adult life, may have feeding difficulties needing gastrostomy, may develop a scoliosis.
3). Type III (Kugelberg-Welander):
Proximal muscle weakness begins after 2 years. Initially walk independently and survive into adult life.
What is the carrier frequency for SMA?
1 in 50.
SMA is caused by mutations in which gene? What kind of mutations cause SMA?
- Caused by mutations in the SMN1 (Survival Motor Neuron) gene - need to have this gene for the motor neurons to survive the pregnancy and throughout adult life.
- 98% of disease alleles are exon 7 deletions and 2% are small intragenic mutations.
Why are carrier tests of parents in SMA cases important?
Carrier tests of parents is important to interpret results for other family members due to the variation in copy numbers of SMN1 in the general population.
Describe SMN2.
- SMN2 is highly homologous to SMN1 and is one factor in determining the phenotype. Those with type III have on average more copies of SMN2 than those with type II or I.
- SMN2 is not a full copy of SMN1 but it can provide some of the protein and so can modify the effects of SMN1 mutation - this is why those with type III usually have milder symptoms.
Outline how SMA may be diagnosed.
- Diagnosis of SMA is often made clinically at first and then confirmed molecularly.
- There will be an EMG which shows fibrillation and muscle denervation.
- Motor and Nerve conduction velocities are normal.
- Creatine kinase levels are normally normal or mildly elevated.
- Muscle histology will show group atrophy of type 1 and muscle fibres.
- Often before muscle biopsies are done genetic tests are carried out.
- Quite often SMA is a common test performed for individuals who present at an early stage with floppiness.
- Differentials of SMA can be quite wide. They include Arthogyroposis multiplex congenita, SMA and repiratory distress (SMARD) with diaphragmatic and intercostal muscle weakness (caused by IGHMBP2), metabolic conditions and other early onset neuromuscular conditions.
How is SMA managed?
- Infants with type I are generally given palliative care with hospice and community nursing involvement.
- In type II physiotherapy, occupational therapy and help with feeding if needed are important. Some may have problems with respiratory failure or scoliosis.
- In type II management is similar but complications are less common.
- The recurrence risk for the core part of the family is going to be 1 in 4 and the phenotype will be very similar. Outside of the core part of the family it gets more difficult to predict phenotype.
