Spinal muscular atrophy

Disorder of lower motor neuron within spinal cord; leads to symmetrical proximal muscle weakness; but cognition is normal.

Autosomal Recessive disorder caused by mutational in the Survival Motor Neuron 1 (SMN1) gene on 5q13, which encodes SMN protein that is essential for survival of anterior motor horn cells.

SMN2 gene produces limited SMN protein which is less functional.

 

Clinical classification:

Type 0 SMA (neonatal form): very severe, often with arthrogryposis; ventilator dependent from birth.

 

Type 1 SMA (Werdnig–Hoffman): “non-sitters”; severe form of hypotonia & areflexia; onset before 6 mo age.

Never able to sit or walk. Poor swallow & tongue fasciculations; Usually die from aspiration or respiratory failure by 2y age.

 

Type 2 SMA (Dubowitz disease): “non-walkers”; intermediate form, onset between 6m – 18m with peripheral weakness, absent reflexes, and scoliosis. Variable swallowing difficulties or respiratory involvement.

Able to sit, but not to walk unaided. Survival into adult life is usual.

 

Type 3 SMA (Kugelberg-Welander disease): mild hypotonia with onset after 18m age, with progressive weakness, abnormal gait and areflexia. Most are to walk independently initially; survive into adult life.

 

Investigations:

– Molecular genetic testing to look for deletion of exons 7 & 8 on SMN1 gene.

– EMG demonstrates abnormal fibrillation pattern

 

Management:

– Genetic confirmation and clinical classification helps towards prognosis. -Management is aimed at alleviating symptoms, reducing complications of muscle weakness and maintaining the quality of life.

– Supportive management depending on severity of feeding difficulties and respiratory function.

– Manage gastro-oesophageal reflux; NGT/ PEG feeds for nutrition;

– Respiratory support: CPAP/ BiPAP/ ventilation as necessary

– Orthopedic input for monitoring & management of postural deformities like hip subluxation, scoliosis, etc

– New therapy with SPINRAZA (Nusinersen) is aimed to modify SMN protein produced by SMN2 gene.

– Involve neurologist, respiratory team, orthopaedics, physiotherapy, occupational therapy, speech therapy, dietitian and community nursing support.