Hereditary Neuropathy Disorders
Hereditary motor, sensory or autonomic neuropathies refer to a group of nerve disorders that lead to weakness, sensory abnormalities or autonomic dysfunction that are due to genetic abnormalities. The genetic abnormality sometimes can be passed on from parents to children. For several of these conditions, the genetic defect is known, and tests are available for the diagnosis and prenatal counseling.
Two most common hereditary neuropathies are:
What is Charcot-Marie-Tooth Disease?
Charcot-Marie-Tooth disease (CMT) is a broad term used to describe a group of inherited neurological disorders characterized by a slowly progressive degeneration of the muscles in the foot, lower leg, hand, and forearm, and a mild loss of sensation in the limbs, fingers, and toes.
Three doctors, Jean-Marie Charcot, Pierre Marie, and Howard Henry Tooth, described for the first time CMT in 1886. Although CMT is one of the most common inherited neuromuscular disorders, it is often misdiagnosed. The number of people in the United States that have CMT is currently estimated to be 125,000 and 2.6 million worldwide.
The symptoms of CMT depend on which form of the disease is inherited, but generally start between mid-childhood and early adulthood. The first signs are usually foot deformities, such as an unusually high arch or flexed “hammer” toes. People with CMT often trip on curbs. Sprained ankles and fractures of the ankles and lower legs are not uncommon. As the disease progresses, muscle weakness and wasting leads to difficulties with walking, running and balance. If the hands are affected, daily activities such as turning doorknobs, fastening buttons, or writing can become difficult.
The disease is slowly progressive and, although many patients need to wear a brace to prevent their feet from dragging, the leg and foot problems are rarely disabling enough to require a wheelchair in the most common forms of CMT. CMT is not a fatal disease, and the disorder does not normally affect normal life expectancy.
Charcot-Marie-Tooth Disease Types 1 & 2
CMT is usually divided into types 1 and 2, depending on which part of the peripheral nerve is affected. Most people have type 1, which affects the myelin sheath (the protective covering of the nerve). About one-third of people with CMT have type 2, which affects the nerve fibers (axons) themselves.
How is it inherited? Today, around 100 different genes are known to cause CMT. However, the PMP22 gene accounts for almost 50% of CMT diagnosis. CMT usually is inherited in an autosomal dominant pattern (as is the case for the PMP22 gene), which means that each child from a parent with CMT has a 50% chance of inheriting the disease. CMT can also be inherited in a recessive or an X-linked pattern.
Charcot-Marie-Tooth Disease Symptoms
CMT symptoms in patients can range from very mild to severe weakness, as well as a degree of sensory disturbances. The more severe symptoms are frequently related to an earlier age of onset. CMT can progress to severe weakness, atrophy, and loss of sensation over time. Not all symptoms and signs may be present in a given person, and the severity of the disease can vary between patients, even within the same family.
Some specific symptoms are:
- Foot drop (foot can’t be picked up or held horizontally)
- Progressive thinning of muscles of the leg (“inverted champagne bottle”) or the foot, with abnormally high arched feet, flat feet and/or hammer toes.
- Decreased sensation or numbness in the foot or leg
- Problems with gait and balance
- Poor hand coordination
- Diminished or absent ankle reflexes
CMT Tests & Evaluations
Several tests and evaluations can be performed to help correctly diagnose CMT disease and guide the genetic testing.
CMT tests and evaluations include:
- Physical examination
- Neurological exam
- Electromyography and a Nerve conduction velocity test
- Nerve and or muscle imaging (echography or magnetic resonance)
- A nerve and/or muscle biopsy may confirm the diagnosis and be performed in selected cases
- Genetic testing is available for most forms of the disease
- Other blood tests such as measuring of the muscle enzyme (CK) or lumbar puncture for cerebrospinal fluid analysis in rare, selected cases
CMT Treatment & Therapy
Although currently there is no cure for CMT, physical therapy, occupational therapy, and moderate physical activity may help maintain muscle strength and endurance. Lightweight lower leg braces, special shoes or shoe inserts can ameliorate gait, prevent ankle sprains and maximize independence. Surgery may be used to correct foot deformities in some patients.
Other treatment options may include:
- Over-the-counter pain medicationfor mild pain
- For moderate-to-severe pain, analgesia specific for neuropathic pain inperipheral neuropathy can be prescribed by your physician
- Shoe inserts can also compensate for loss of sensation
What is HNPP?
Hereditary neuropathy with liability to pressure palsies (HNPP) is a relatively common, though under-diagnosed, hereditary disorder in which a fairly mild pressure or trauma to a single nerve results in episodes or periods of numbness and weakness, similar to an arm or leg going to sleep. Unlike a limb going to sleep for a few seconds, each episode of numbness can last from several minutes to several days or months. The most common sites are the wrists, with carpal tunnel syndrome, the elbows or knees. HNPP is inherited in an autosomal dominant manner, which means that each child of a person with HNPP has a 50% chance of inheriting the genetic mutation. It may be misdiagnosed as Charcot-Marie-Tooth disease, an isolated pressure palsy or Bell’s Palsy.
HNPP Symptoms
HNPP can a progressive hereditary disorder, but the symptoms can be so mild that they go unnoticed. For some people, there are years between episodes, while others have mild symptoms that progress at a steady rate.
(Not all symptoms and signs may be present.)
- Partial or total weakness of a limb
- Unable to use certain muscles of the arm (can’t reach, wash hair, eat) or hand (difficulty gripping things or grasping small objects) or face
- Episodes of numbness or tingling that do not go away
- Diminished or absent ankle reflexes
- Other symptoms such as fatigue, muscle cramps or leg/ankle foot swelling may be associated
HNPP Testing
(Not all evaluation and tests may be necessary.)
- Physical examination
- Neurological exam
- Electromyography and Nerve conduction velocity test
- Nerve imaging
- Nerve biopsy
- Genetic blood tests
HNPP Treatment
Avoiding positions that can create pressure on a nerve, such as leaning on elbows, crossing legs or ankles, or sitting for too long without changing position is the principal measure to prevent episodes of weakness and tingling. In this line a person with HNPP should avoid:
- Prolonged activity on hands and knees that could cause nerve compression
- Sitting with legs crossed, tailor-style
- Sitting in one position too long without readjusting
- Holding the telephone in one position too long
- Tying shoes too tight or using tight shoe straps
- High heels, which can make toes numb
An adaptation of the environment, specially at work, can also be beneficial in reducing episodes of palsy. Take safety measures to compensate for loss of sensation and ask your doctor about special therapeutic shoes (which may be covered by Medicare and other insurance).
Symptomatic treatment of pain with over-the-counter pain killers or specific analgesia for neuropathic pain can also be helpful in patients experiencing sensory disturbances.
A Story of Hope:
Joe and Dana Bacon
Joe and Dana Bacon’s story is a story of hope. They personify all that is good in this world: love, strength, determination. They make you BELIEVE anything is possible.
The Foundation for Peripheral Neuropathy spoke to Joe and Dana about their life, their inspirations, Dana’s battle with and acceptance of small fiber neuropathy, and Joe’s upcoming Race for a Cure at the Baltimore Marathon.