Spinal Muscular Atrophy (SMA) is a hereditary neuromuscular disorder characterised by progressive degeneration of the anterior horn cells in the spinal cord, leading to symmetrical weakness and wasting of skeletal muscles. Despite its rarity, it is one of the most common genetic causes of infant mortality. The underlying defect lies in the SMN1 gene (Survival Motor Neuron 1), located on chromosome 5q13, which encodes a protein essential for motor neuron maintenance and survival.

Loss of SMN1 function results in reduced levels of the SMN protein, impairing motor neuron integrity. A paralogous gene, SMN2, produces limited functional protein and partly modifies disease severity - the more SMN2 copies a patient has, the milder the phenotype. Clinically, SMA encompasses a spectrum from the severe Type 1 (Werdnig–Hoffmann), presenting in infancy with respiratory failure, to the milder Type 3–4 forms manifesting in later childhood or adulthood with slowly progressive proximal weakness.

💡 Teaching tip: SMA is a lower motor neuron disorder - note the absence of spasticity, brisk reflexes, or Babinski signs. Fasciculations (especially of the tongue) and hypotonia are hallmark findings. In contrast, upper motor neuron diseases like MND show the opposite pattern.

In the UK, newborn genetic screening for SMA is expanding, allowing early identification before symptom onset. Disease-modifying therapies such as Nusinersen (Spinraza®), Risdiplam (Evrysdi®), and Onasemnogene abeparvovec (Zolgensma®) have revolutionised outcomes, especially when given presymptomatically. Multidisciplinary management remains essential - involving neurology, respiratory care, nutrition, and physiotherapy teams.

📊 Comparison of Spinal Muscular Atrophy (SMA) Types

Type	Other Name	🧒 Age of Onset	💪 Motor Function	🫁 Respiratory Involvement	📉 Prognosis
I	Werdnig–Hoffman Disease	Birth – 6 months	Never sit unaided, severe hypotonia, weak cry, tongue fasciculations	Severe, early respiratory failure	Life expectancy < 2 years (improved with modern therapy)
II	Intermediate SMA	6 – 18 months	Sit but never walk unaided, proximal weakness, tremor	Progressive, often scoliosis and restrictive lung disease	Survival into adolescence/adulthood possible
III	Kugelberg–Welander Syndrome	2 – 10 years	Walk initially but progressive difficulty; proximal weakness, frequent falls	Milder, but respiratory support may be needed later	Many survive into adulthood; slower progression
IV	Adult-onset SMA	Adolescence to adulthood (>20 years)	Mild proximal weakness, gradual progression	Minimal or absent	Normal life expectancy, slow decline

🧬 All SMA types share the same genetic cause (SMN1 mutations), but severity depends on SMN protein levels, often influenced by copy number of the SMN2 “backup gene.” Modern therapies (Nusinersen, Risdiplam, Zolgensma) have dramatically changed prognosis across all types.

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Spinal Muscular Atrophy (SMA) 🧠

🧠 Introduction

📊 Comparison of Spinal Muscular Atrophy (SMA) Types

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