Proximal spinal muscular atrophy

Proximal Spinal Muscular Atrophy

Proximal Spinal Muscular Atrophy (SMA) is a genetic disorder characterized by weakness and wasting (atrophy) in the voluntary muscles, particularly those closest to the center of the body, such as the shoulders, hips, and back. It is caused by the degeneration of motor neurons in the spinal cord and the brainstem, which are responsible for muscle movement.

Etiology

Proximal Spinal Muscular Atrophy is primarily caused by mutations in the SMN1 gene, which encodes the survival motor neuron (SMN) protein. This protein is crucial for the maintenance of motor neurons. The most common mutation is a deletion of exon 7 in the SMN1 gene. The severity of the disease is often influenced by the number of copies of the SMN2 gene, a nearly identical gene that can partially compensate for the loss of SMN1.

Classification

SMA is classified into several types based on the age of onset and the highest physical milestone achieved:

• Type 0 (Prenatal SMA): The most severe form, with symptoms present before birth.
• Type 1 (Werdnig-Hoffmann disease): Onset before 6 months of age, with severe muscle weakness and poor motor development.
• Type 2 (Intermediate SMA): Onset between 6 and 18 months, with the ability to sit but not walk unaided.
• Type 3 (Kugelberg-Welander disease): Onset after 18 months, with the ability to walk but with progressive weakness.
• Type 4 (Adult-onset SMA): Onset in adulthood, with mild to moderate muscle weakness.

Pathophysiology

The loss of SMN protein leads to the degeneration of lower motor neurons in the anterior horn of the spinal cord. This results in muscle denervation and atrophy. The proximal muscles, such as those of the shoulders, hips, and back, are most affected, leading to the characteristic pattern of weakness.

Clinical Features

Patients with proximal SMA typically present with:

• Muscle Weakness: Predominantly in the proximal muscles.
• Hypotonia: Reduced muscle tone.
• Areflexia: Absence of reflexes.
• Respiratory Complications: Due to weakness of the intercostal muscles and diaphragm.
• Feeding Difficulties: In severe cases, due to bulbar muscle weakness.

Diagnosis

Diagnosis of SMA is based on clinical examination, genetic testing for SMN1 mutations, and electromyography (EMG) to assess muscle function. Genetic testing is the definitive method for diagnosis.

Management

Management of SMA is multidisciplinary and includes:

• Genetic Counseling: For affected families.
• Physical Therapy: To maintain muscle function and prevent contractures.
• Respiratory Support: Non-invasive ventilation may be required.
• Nutritional Support: To address feeding difficulties.
• Pharmacological Treatments: Such as Nusinersen (Spinraza), Risdiplam (Evrysdi), and gene therapy with Onasemnogene abeparvovec (Zolgensma).

Prognosis

The prognosis of SMA varies depending on the type. Type 1 SMA has the most severe prognosis, often leading to early mortality without intervention. Types 2 and 3 have a more variable course, with many patients living into adulthood with supportive care.

Also see

• Motor neuron disease
• Muscular dystrophy
• Genetic disorders
• Neuromuscular junction

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External links

• Comprehensive information from the National Institute of health.
  

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