Hereditary Neuropathy affects nerves that connect the brain and spinal cord to muscles and to sensory cells that detect pain, temperature, and touch. People with this condition can develop open sores (ulcers) in their feet and hands that are slow to heal.
Genetic testing can help diagnose hereditary neuropathies and identify specific gene mutations. Molecular diagnostic evaluation can also identify other potential triggers of symptoms and give insight into future symptoms that may appear.
Symptoms
Hereditary neuropathies affect the nerves outside the brain and spinal cord (peripheral nerves). These nerves connect the brain and spinal cord with muscles and sensory cells that detect touch, pain and temperature. They also control involuntary functions such as sweating and blood pressure. Many hereditary neuropathies cause a progressive loss of function (and sensation) in the nerves that lead to your feet and hands. These symptoms may develop at any age from adolescence to late adulthood. They may differ in severity and specific symptoms, depending on the type of hereditary neuropathy you have. Some examples include Charcot-Marie-Tooth disease, Hereditary Sensory Neuropathy with Liability to Pressure Palsies and Dejerine-Sottas syndrome.
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Most hereditary neuropathies are inherited, meaning they run in families. But some are acquired, developing after birth due to certain conditions or injuries and as a side effect of medications. Hereditary neuropathies can be divided into two categories: autosomal dominant and autosomal recessive. Autosomal dominant hereditary neuropathies are passed down from parent to child; autosomal recessive hereditary neuropathies occur when one copy of a gene has been lost and a new, variant gene is inherited.
Symptoms vary widely, depending on the type of hereditary neuralpathy you have. Inheritable forms of neuropathy usually involve both motor and sensory nerves, and symptoms tend to affect the legs more than the arms. Many people with hereditary neuropathy have a combination of symptoms including numbness and tingling in the feet and hands, muscle weakness, reduced balance and coordination and impaired sweating. Some types of hereditary neuropathy also lead to painful open sores (ulcers) in the feet and hands, often called whitlows. These ulcers are slow to heal and can become infected, causing serious complications such as limb amputation.
Some health conditions can increase your risk of hereditary neuropathies, such as diabetes and obesity. People with hereditary neuropathies can take steps to reduce their risk by maintaining a healthy weight, eating a balanced diet and not smoking. They can also prevent hereditary neuropathies by avoiding activities that put pressure on the nerves, such as carrying heavy bags or leaning on their elbows or crossed legs.
Diagnosis
Inheritable neuropathies can affect the motor, sensory and autonomic nerves in different ways. Symptoms can include pain, numbness and muscle weakness. Genetic testing can help determine if you have an inherited gene that causes one of these disorders.
Each person’s genome contains some 30 million “letters of the alphabet” called single nucleotide polymorphisms (SNP). Some of these SNPs are linked to a higher risk for certain health conditions, including hereditary neuropathies. Health conditions like diabetes and obesity also increase your risk for hereditary neuropathies.
Because hereditary neuropathies are caused by a variety of genes, there are many different types of these disorders. Some are progressive and cause muscle weakness over time. Other types are more gradual and result in numbness or weakness of the feet or hands.
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It can be difficult to diagnose hereditary neuropathies, especially in the early stages. A physical exam and review of the symptoms is important. Medical history and family history can also be helpful. Nerve conduction studies and a nerve biopsy can help rule out other causes of the neuropathy. In the past, some hereditary neuropathies were diagnosed based on the onset of symptoms and a family history. Other hereditary neuropathies were diagnosed primarily on the basis of abnormal findings on electromyography and nerve biopsies.
Hereditary peripheral neuropathies (HPN) are a group of hereditary degenerative disorders that cause numbness or weakness of the feet and hands. They are characterized by slowing of the nerve fibers on an electromyography test and by a loss of the small bundles of myelinated nerve fibers that facilitate speedy transmission of nerve impulses in the extremities.
Currently, routine genetic screening for hereditary motor neuropathy (HMN) and hereditary sensory-autonomic neuropathies (HSAN) is not feasible due to low mutation frequencies. If performed, the EFNS recommends BSCL2 be screened in patients with HMN and NTRK1 in patients with CMT2B or HSAN. SEPT9 may be screened in HSAN1E patients with hereditary neuralgic amyotrophy with anhidrosis (CIPA, a sub-phenotype of HSAN1).
The Neuropathy Association provides support for people with hereditary neuropathies. The organization also helps fund research and provides education about hereditary neuropathies.
Treatment
Hereditary neuropathies are a group of genetic disorders that cause gradual damage to peripheral nerves. These nerves carry signals between the brain and spinal cord, and then to the body’s muscles and sensory organs. Hereditary neuropathies can affect motor or sensory nerves or autonomic nerves that control involuntary body processes, such as sweating and blood pressure. Symptoms vary from person to person and can be mild or severe. They may occur at any age, but tend to get worse over time.
Often, the most common symptom of hereditary neuropathy is numbness and tingling in the feet or hands. Muscle weakness may also develop, especially if the hereditary neuropathy affects motor nerves that control muscle movement. Other symptoms include sensitivity to touch or pain, difficulty standing for long periods of time and difficulty with walking. In some hereditary neuropathies, the abnormalities of the nerves can lead to a drop in blood pressure and slow heart rate, known as orthostatic hypotension.
Genetic hereditary peripheral neuropathies can be difficult to diagnose, as symptoms can be mild and may not be apparent until adulthood. Previously, diagnosis was made by a physical exam, review of family history and diagnostic testing, including digital nerve conduction studies (EMG/NCS), magnetic resonance imaging and a nerve biopsy. The nerve biopsy is usually a painful procedure, but it can provide important information such as the presence of “onion-bulbs” on the surface of the nerve, which indicate recurrent demyelination and remyelination.
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With recent advances in genetics, however, many hereditary neuropathies can now be diagnosed with a simple blood test. For example, a genetic mutation in HSAN1 causes hereditary peripheral neuropathy with liability to pressure palsies (HNPP), a condition marked by recurrent episodes of numbness, tingling and loss of muscle function in the affected arm or leg. With the development of these tests, the prognosis for hereditary neuropathies has improved considerably.
In addition, some trials have shown that certain drugs can improve neuropathic symptoms, including the oral drug L-serine for hereditary neuropathies associated with HSAN1 and PTX3003 for CMT1A. However, these trials were often small and relied on clinical scales to measure neuropathy, rather than examining changes in nerve conduction or using the validated Hereditary Peripheral Neuropathy Score (HPNS). It is critical that future clinical trials examine more patients with HNPS, use the validated HPNS and compare outcomes to natural history cohorts.
Prevention
The most important preventive measures involve controlling medical conditions that increase the risk of neuropathy, including diabetes, alcoholism, hypothyroidism and kidney disease. Regular exercise, a healthy diet and adequate vitamin B-12 supplementation may also help. People with hereditary neuropathies should seek genetic counseling to determine whether they are at increased risk of passing on a mutation to their children.
Peripheral neuropathy develops when damage occurs to the peripheral nerves, which act as a communication bridge between your central nervous system and your body. Motor nerves control muscle movement, sensory nerves carry information about things you feel — such as pain, temperature or touch — to your brain and autonomic nerves regulate involuntary body processes such as heartbeat and breathing. Symptoms can range from mild, annoying tingling to severe burning, painful, and sometimes even crippling muscle weakness.
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A health care professional will use a physical exam and laboratory tests to diagnose hereditary neuropathy. In some cases, a nerve biopsy or skin biopsy may be necessary to find the cause of the neuropathy. These procedures involve removing a small portion of a nerve or a piece of skin, respectively, to see the number of nerve endings and determine the type of neuropathy.
Medications used to treat hereditary neuropathies include antidepressants, anti-seizure medications, anti-retroviral drugs and immune system suppressants. In addition, anti-inflammatory medications can be helpful in improving mild symptoms.
If not treated, hereditary neuropathies can lead to serious complications. For example, untreated Charcot-Marie-Tooth disease can eventually cause progressive loss of muscle bulk in the legs and feet and foot deformities such as high arches and hammertoes. Similarly, untreated Hereditary Neuropathy with Liability to Pressure Palsies can lead to recurrent episodes of limb paralysis triggered by strenuous activity.
Symptoms of hereditary neuropathies can begin at any age, although they are more likely to appear during infancy, childhood or early adulthood. Keeping medical conditions under control, eating a nutritious diet and using assistive devices can help prevent neuropathy symptoms from worsening. Installing handrails in the bathroom and walking only in well-lit areas can reduce falls, which are a common cause of injury among people with hereditary neuropathies.
