Hereditary neuralgic amyotrophy

Overview

Hereditary neuralgic amyotrophy (HNA) is a rare, inherited neurological disorder characterized by recurrent episodes of severe pain, followed by weakness and atrophy of the shoulder, arm, and hand muscles. It primarily affects the brachial plexus - a network of nerves that control muscle movement and sensation in the upper limbs. HNA is distinct from the more common idiopathic form of neuralgic amyotrophy (also known as Parsonage–Turner syndrome) in that it follows a familial pattern and typically has an earlier age of onset, often beginning in childhood or adolescence.

Causes

HNA is caused by mutations in the SEPT9 gene, which is located on chromosome 17q25. The SEPT9 gene plays a role in cell division and intracellular transport. The condition is inherited in an autosomal dominant pattern, meaning a mutation in one copy of the gene is sufficient to cause the disorder. While the exact mechanism is not fully understood, the mutation appears to make nerves more vulnerable to inflammation or injury, often triggered by infections, physical stress, surgery, or immunological stimuli.

Symptoms

Symptoms of hereditary neuralgic amyotrophy typically begin in childhood or early adulthood and recur throughout life. Episodes often occur suddenly and affect one side of the body more than the other. Common symptoms include:

• Sudden, severe shoulder or upper arm pain: Often the first sign of an attack

• Muscle weakness and atrophy: Occurs days to weeks after the onset of pain, affecting the shoulder, upper arm, forearm, or hand

• Sensory disturbances: Such as numbness or tingling in the affected limb

• Limited range of motion: Due to weakness and pain

• Recurrent episodes: Multiple attacks may occur over a lifetime, sometimes affecting different nerves

• Facial or diaphragmatic involvement: Less common, but may be seen in some cases

Some individuals may also have minor physical anomalies, such as hypotelorism (closely spaced eyes) or cleft palate, though these features are not always present.

Diagnosis

Diagnosis of HNA is based on clinical history, family history, and confirmatory genetic testing. The following steps are typically involved:

• Medical history: Recurrent, painful episodes affecting the upper limbs with a family pattern

• Neurological examination: Evidence of muscle weakness, atrophy, and sensory loss in affected regions

• Electromyography (EMG): Helps confirm nerve damage by evaluating electrical activity in muscles

• Nerve conduction studies: Assess the function of peripheral nerves

• Genetic testing: Detection of mutations in the SEPT9 gene confirms the diagnosis

It is important to distinguish HNA from other causes of brachial plexopathy or neuropathy, such as trauma or autoimmune conditions.

Treatment

There is no cure for hereditary neuralgic amyotrophy, and treatment focuses on managing symptoms and reducing the impact of attacks. Treatment options include:

• Pain management: NSAIDs, corticosteroids, or neuropathic pain medications (e.g., gabapentin)

• Physical therapy: To maintain strength and mobility during and after episodes

• Occupational therapy: Assists with daily functioning and adaptive strategies

• Corticosteroids: May help shorten the duration and severity of acute attacks

• Avoidance of triggers: Including infections, vaccinations, and physical overexertion

Multidisciplinary care is often beneficial to support long-term function and quality of life.

Prognosis

The prognosis of hereditary neuralgic amyotrophy varies. While the condition is chronic and episodic, many individuals recover partially or fully between attacks. However, repeated episodes can lead to cumulative nerve damage, resulting in persistent weakness or disability in some cases. Early treatment during attacks and ongoing rehabilitation can help preserve muscle strength and reduce complications. Genetic counseling is recommended for affected families due to the hereditary nature of the disorder.