Spinal Muscular Atrophy (SMA)

Original Editor - Evelin Milev Top Contributors - Evelin Milev, Jeremy Bryan, Lucinda hampton, Nikhil Benhur Abburi, Kim Jackson, Rucha Gadgil, Momina Khalid, Aminat Abolade, Rachael Lowe and Meaghan Rieke

Introduction

Spinal Muscular Atrophy (SMA) is a genetic condition under the scope of the neuromuscular disorders. It is characterised by degeneration of alpha motor neurons in the spinal cord that affects the control of voluntary muscle movement. The disease is characterised as an autosomal recessive condition with prevalence of approximate 1 in 6-10,000 births affected by SMA with a carrier frequency of 1 in 35-70. Classification of SMA type depends on the age of onset and the highest level of motor function achieved.

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Clinically Relevant Anatomy

SMA is caused by deficiency of a motor neuron protein called SMN (Survival Motor Neuron). This protein is essential for normal motor function and the lack of it is caused by genetic flaws on chromosome 5 in the gene SMN1. The neighbouring SMN2 gene can compensate some of the functions of SMN1 and this is where some of the pharmaceutical companies trying to develop a drug which can enhance the effect of SMN2.

Mechanism of Injury / Pathological Process

Spinal Muscular Atrophy is an autosomal recessive condition due in most cases to the homozygous deletion of the SMN1 gene. This means that both parents of the affected individual are only carriers of the affected gene. Therefore, they are not going to present with any symptoms of the disease and this is what makes SMA difficult to foreseen and apply preventable measures.

Clinical Presentation

Spinal Muscular Atrophy (SMA) is the second most common neuromuscular disorder of childhood. People affected by the mildest types of SMA have proximal weakness and impaired ambulation. Furthermore, fatigue is a symptom to present in almost every case of SMA which may also lead to impaired function and endurance. Current research in the area shows that there is good correlation between upper and lower limb function in patients with the disease. There are several types of SMA, which start at different ages and may present with various phenotype.

Types of SMA:

• SMA type I - affects babies less than six months old and is the most severe type of the disease
• SMA type II - develops in babies between 7 and 18 months old. This type is less severe than type I and most children survive into adulthood and can live long, fulfilling lives.
• SMA type III - appears after 18 months of age and is the least severe type affecting children. SMA type III has been divided into two further sub-categories: SMA IIIa and SMA IIIb - according to the time when the first symptoms of the condition appears (if before or after 3 years of age).
• SMA type IV - this type of SMA patients are diagnosed in adulthood and they present with only mild problems.

Diagnostic Procedures

Diagnoses could be made by prenatal screening or by gene panel investigation and/or muscle biopsy. In early stages the diagnose may be suspected due to symptoms like floppiness and muscular weakness. Children with type I SMA can present with lack of head control, minimal to absent anti-gravity movements and severe respiratory complications.

The first steps in diagnosing someone with SMA would be by taking a full clinical examination and family history. As mentioned above, a blood test might be required to look at the amount of creatine kinase (CK), an investigation to indicate if muscle damage has occurred. High levels levels of the CK in the blood is not damaging itself, but it is an important indicator of a muscle disorder condition. Further investigation will probably include a genetic testing as this is the most accurate way to diagnose if patient has Spinal Muscular Atrophy.

Outcome Measures

There are several outcome measures which can be used to detect changes in the natural history of the patients with SMA. These tools should be appropriate selected according to the age and severity of the disease.

Six-Minute Walking Test (6MWT)

The Six-Minute-Walking-Test can be safely performed in ambulant patients with SMA. It has been proven to detect fatigue-related changes in this population of patients and also correlates with other established outcome measures for patients with spinal muscular atrophy.

Management / Interventions

Physiotherapy

• Assessment of the patient with neuromuscular disease and particularly with SMA is of a great importance. Looking at baseline function, joint range and power will assist the physiotherapist to follow on the progression of the condition.
• Orthotics
• Splinting
• Taping
• Management of contractures
• Exercise and activity

Differential Diagnosis

Neuromuscular conditions:

• Duchenne Muscular Dystrophy
• Charcot-Marie-Tooth
• Amiotrophic Lateral Sclerosis
  

Resources and Useful Links

SMA REACH UK - Information Page

Spinal Muscular Atrophy Support UK