Werdnig–Hoffman Disease (Spinal Muscular Atrophy Type 1)
Related Subjects:
|Kugelberg-Welander Syndrome (Spinal Muscular Atrophy Type III)
|Werdnig–Hoffman Disease (Spinal Muscular Atrophy Type 1)
|Spinal Muscular Atrophy (SMA)
|Poliomyelitis
|Post Polio Syndrome
|Anterior Horn Cell diseases
|Transverse myelitis
|Acute Disseminated Encephalomyelitis
|Cervical spondylosis
|Spinal Cord Anatomy
|Acute Disc Prolapse
|Spinal Cord Compression
|Spinal Cord Haematoma
|Foix-Alajouanine syndrome
|Cauda Equina
|Conus Medullaris syndrome
|Anterior Spinal Cord syndrome
|Central Spinal Cord syndrome
|Brown-Sequard Spinal Cord syndrome
👶 About
- Werdnig–Hoffman Disease, also called Spinal Muscular Atrophy (SMA) Type 1, is the most severe and common form of SMA presenting in infancy.
- It causes progressive muscle weakness and wasting due to loss of anterior horn cells in the spinal cord.
- Incidence: ~1 in 10,000 live births.
🧬 Aetiology
- Caused by mutations in the SMN1 gene on chromosome 5q13, leading to reduced survival motor neuron protein.
- Inheritance: Autosomal recessive (25% recurrence risk if both parents are carriers).
- Pathology: Degeneration of anterior horn cells → progressive denervation of skeletal muscles.
🩺 Clinical Features
- 💡 Often suspected antenatally: reduced fetal movements.
- Severe flaccid hypotonia ("floppy infant") at birth or within 6 months.
- Characteristic posture: flexed arms, extended legs, frog-like positioning.
- Weak cry and difficulty swallowing (→ aspiration pneumonia risk).
- Tongue fasciculations (high-yield exam feature 👅⚡).
- Respiratory involvement: paradoxical breathing (diaphragmatic breathing with weak intercostals), recurrent chest infections, respiratory failure.
- May present with arthrogryposis multiplex congenita in utero.
🔍 Investigations
- Electromyography (EMG): Denervation (fibrillations, positive sharp waves).
- Creatine kinase (CK): Often normal or mildly elevated.
- Genetic testing: Confirms homozygous deletions/mutations in SMN1.
💊 Management
- Supportive care:
- 🫁 Respiratory support (non-invasive ventilation, suctioning, tracheostomy in some).
- 🍽️ Nutritional support: NG tube or gastrostomy for feeding and aspiration prevention.
- 🧑🦽 Physiotherapy and postural support.
- Disease-modifying therapies:
- Nusinersen (Spinraza): Antisense oligonucleotide that increases SMN protein production.
- Onasemnogene abeparvovec (Zolgensma): Gene replacement therapy, single-dose IV infusion — best outcomes when given early.
- Risdiplam: Oral SMN2 splicing modifier, used in some centres.
📉 Prognosis
- Without treatment: most infants die by 2 years (often by respiratory failure); rarely survive beyond 4 years.
- With new therapies, survival and motor outcomes are improving if started early (especially before symptom onset).
- Genetic counselling for parents is essential to discuss carrier status and future pregnancies.
