Werdnig–Hoffmann disease

Werdnig–Hoffmann Disease

Werdnig–Hoffmann disease, also known as spinal muscular atrophy type 1 (SMA1), is a severe genetic disorder characterized by the degeneration of motor neurons in the spinal cord and brainstem, leading to muscle weakness and atrophy. It is the most severe form of spinal muscular atrophy and is typically diagnosed in infancy.

Etiology

Werdnig–Hoffmann disease is caused by mutations in the SMN1 gene, which is responsible for producing the survival motor neuron (SMN) protein. This protein is crucial for the maintenance of motor neurons. The absence or deficiency of SMN protein leads to the progressive degeneration of these neurons, resulting in muscle weakness and atrophy.

Clinical Presentation

Infants with Werdnig–Hoffmann disease typically present with symptoms within the first six months of life. Common clinical features include:

• Severe muscle weakness and hypotonia (floppy baby syndrome)
• Poor head control
• Difficulty swallowing and feeding
• Respiratory distress due to weakness of the intercostal muscles
• Absence of deep tendon reflexes

Diagnosis

Diagnosis of Werdnig–Hoffmann disease is based on clinical examination, genetic testing, and electromyography (EMG). Genetic testing confirms the diagnosis by identifying mutations in the SMN1 gene.

Management

There is currently no cure for Werdnig–Hoffmann disease, and management focuses on supportive care. This includes:

• Nutritional support, often requiring feeding tubes
• Respiratory support, such as non-invasive ventilation or tracheostomy
• Physical therapy to prevent contractures and maintain joint mobility

Recent advances in gene therapy, such as the use of nusinersen and onasemnogene abeparvovec, have shown promise in altering the disease course.

Prognosis

The prognosis for infants with Werdnig–Hoffmann disease is poor, with most affected children not surviving past early childhood due to respiratory complications. However, with advances in supportive care and new therapies, some children are living longer and achieving developmental milestones.

History

The disease is named after the Austrian neurologist Guido Werdnig and the German neurologist Johann Hoffmann, who independently described the condition in the late 19th and early 20th centuries.

Also see

• Spinal muscular atrophy
• SMN1
• Nusinersen
• Gene therapy