Hereditary Motor and Sensory Neuropathy (HMSN)

Also Known As:

• Charcot-Marie-Tooth disease (CMT)
• Hereditary polyneuropathy
• Hereditary neuropathy

Characteristics

HMSN is a collective term for a group of hereditary disorders affecting the nerves. It involves damage to nerves that transmit signals from sensory organs to the brain (sensory) and from the brain to the muscles (motor). This disruption leads to weakened muscles, atrophy (muscle thinning), and sensory disturbances such as reduced pain perception.

• HMSN Type 1 (Demyelinating): Damage to the insulating myelin sheath surrounding nerve fibers reduces signal transmission.
• HMSN Type 2 (Axonal): Direct damage to the nerve fibers (axons) decreases their number over time.
• X-linked HMSN: A mixed form that is more severe in men, involving both demyelination and axonal damage.

Prevalence and Disease Course

HMSN affects at least 1 in 10,000 people. Symptoms of HMSN 1 often appear in childhood around age 10, while HMSN 2 typically has a later onset, though it can also occur in younger individuals. Women with X-linked HMSN usually develop symptoms later in life.

The disease progresses slowly and primarily affects the arms and legs, with the first signs appearing in the extremities furthest from the spine, such as toes, feet, and lower legs. Early symptoms include difficulty walking, frequent tripping, and ankle instability. Children may struggle to hop, jump, or run. A distinctive high-stepping gait (foot drop) with flapping feet is common.

Over time, muscle weakness leads to physical changes:

• Feet: Development of high arches, flat feet, or claw toes.
• Lower legs: Visible thinning, sometimes referred to as “stork legs.”
• Hands and arms: Weakened grip strength, difficulty with fine motor tasks, and thin fingers and forearms.

Less than 10% of individuals experience weakness in muscles closer to the torso, such as the thighs and upper arms, which may lead to wheelchair dependency. Sensory disturbances, including reduced touch and pain sensation, are always present but often less noticeable. A diminished pain response increases the risk of unnoticed injuries.

Cause

HMSN results from a genetic mutation affecting nerve fibers. The disorder can arise from various genetic defects, with inheritance patterns as follows:

• Autosomal Dominant (HMSN 1 and 2): Affected parents have a 50% chance of passing the condition to their children.
• X-linked HMSN: Passed through the X chromosome. Men with one X chromosome are always affected, while women with two X chromosomes may have mild or no symptoms. Men cannot pass the gene to their sons but transmit it to all daughters.

Treatment

There is currently no cure for HMSN. Treatment focuses on managing symptoms and improving quality of life:

• Therapies: Physical and occupational therapy help maintain muscle strength, improve posture, and prevent overuse injuries.
• Assistive Devices: Customized footwear, walking aids, or other supportive tools can enhance daily functioning.
• Exercise: Targeted muscle exercises can prevent complications from muscle and joint strain.

Effective management strategies aim to minimize the impact of the disease on mobility and independence.