Paramyotonia congenita

Paramyotonia congenita

Paramyotonia congenita also called Eulenburg disease, Von Eulenberg’s disease or paralysis periodica paramyotonia, is a rare non-progressive genetic disorder that affects muscles used for movement (skeletal muscles), mainly in the face, neck, arms, and hands. Symptoms begin in infancy or early childhood and are always apparent by the teenage years, people with paramyotonia congenita experience bouts of sustained muscle tensing (myotonia) that prevent muscles from relaxing normally and lead to muscle weakness. Myotonia causes muscle stiffness and unlike many other forms of myotonia where individuals suffer symptoms during both rest or after exercise, paramyotonia congenita develops muscle stiffness with exercise and worsen with repeated movements and can be induced by muscle cooling or exposure to cold temperatures. This stiffness chiefly affects muscles in the face, neck, arms, and hands, although it can also affect muscles used for breathing and muscles in the lower body. Some episodes of muscle stiffness may also be induced by hyperkalemia or hypokalemia, starvation, hypothyroidism and pregnancy 1); affected individuals are instructed to avoid certain food products rich in potassium.

Most people—even those without muscle disease—feel that their muscles do not work as well when they are cold. This effect is dramatic in people with paramyotonia congenita. Exposure to cold initially causes muscle stiffness in these individuals, and prolonged cold exposure leads to temporary episodes of mild to severe muscle weakness that may last for several hours at a time. In addition, it can become more severe with exercise. The muscle stiffness in these individuals can be alleviated by warm temperatures. Sudden overexertion can trigger muscle stiffness and overall weakness that can take several days to completely resolve. Paramyotonia congenita can make small everyday activities difficult, such as letting go of small objects (e.g. pens or door knobs).

Some patients with more severe paramyotonia congenita can experience shortness of breath or tightness in their chest muscles.

Some older people with paramyotonia congenita develop permanent muscle weakness that can be disabling.

Paramyotonia congenita is caused by mutations in the SCN4A gene and is inherited in an autosomal dominant pattern 2). Most individuals with a SCN4A gene mutation have symptoms; however, there are a few who remain unaffected and are known as “carriers”.

Paramyotonia congenita is an uncommon disorder; it is estimated to affect fewer than 1 in 100,000 to 1 in 250,000 people 3).

I was diagnosed with paramyotonia congenita when I was young. If I have children, would pregnancy cause serious health issues related to my condition?

There is limited information in the medical literature regarding the effects of pregnancy in individuals with paramyotonia congenita, as this condition is quite rare. One article described the experience of four women with this condition: one experienced worsening of her symptoms during pregnancy, whereas three did not 4). Another article on paramyotonia congenita and related conditions listed pregnancy as a possible trigger of muscle weakness in affected women 5). Though there is little information about pregnancy in women with paramyotonia congenita, general information about women affected by other myotonia conditions suggests symptoms may worsen during pregnancy, but quickly return to usual levels after pregnancy 6).

Avoiding exposure to cold air, adequate relief of labor pain and avoidance of electrolyte imbalance, particularly potassium, ensure safe labor and delivery for patients with paramyotonia congenita 7). There are several anticipated complications and/or triggers for myotonia crisis. Obstetric complications include uterine atony and prolonged labor requiring cesarean delivery, whereas anaesthetic complications may result from medications used for general anaesthesia. Intubation using suxamethonium for rapid sequence induction may induce myotonic contracture and masseter spasm leading to failed intubation 8). Subsequently, chest stiffness may disrupt mechanical ventilation. For possible triggers, there might be an unpredictable sensitivity towards non-depolarizing muscle relaxants leading to postoperative prolonged block which may occur after reversal with neostigmine 9). For that reason, Buzello et al. 10) advocated the use of atracurium or cisatracurium which have spontaneous metabolism and do not require reversal. In general, rocuronium has been commonly used under neuromuscular block monitoring, and sugammadex has been the choice of reversal agent instead of neostigmine 11). Another trigger hyperkalemia which is either induced by suxamethonium or its presence can aggravate myotonia. Although the risk of malignant hyperthermia is very low for paramyotonia congenita, volatile agents may lead to postoperative shivering and subsequently myotonia 12). Spinal and epidural anaesthesia has been safely used both for caesarean and vaginal deliveries 13). Frossard et al. 14) described the successful management of neuraxial labor analgesia using 0.02% ropivacaine with sufentanil via epidural catheter. Because both general and regional anaesthesia techniques may pose the risk of disturbing the thermoregulation, it is wise to avoid testing sensory block level with ice and to keep the ambient temperature warm in the labor suite and operating room similar. Additionally, providing thermal comfort with hot air blanket should be considered during and after surgery.

Paramyotonia congenita causes

Mutations in the SCN4A gene on chromosome 17q23 cause paramyotonia congenita. The SCN4A gene provides instructions for making a protein that is critical for the normal function of skeletal muscle cells. The SCN4A protein forms channels that control the flow of sodium ions into these cells. Skeletal muscles move the body; muscle contractions pull on tendons, which are attached to the bones and causes the body to move. For the body to move normally, skeletal muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of positively charged atoms (ions) (e.g. potassium and sodium) through channels into the skeletal muscle cells. These atoms carry electrical impulses necessary for normal function of the muscle cells. However, a mutation of the SCN4A gene alters the structure of the sodium channels.

Mutations in the SCN4A gene alter the usual structure and function of sodium channels. The altered channels cannot effectively regulate the flow of sodium ions into skeletal muscle cells and the ratio of sodium and potassium becomes unbalanced. The abnormal ratio interferes with normal muscle contraction and relaxation, causing bouts of muscle weakness and stiffness.

Paramyotonia congenita inheritance pattern

Paramyotonia congenita is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In many cases, an affected person has one parent with the condition. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.

In some individuals, paramyotonia congenita is due to a spontaneous (de novo) genetic mutation that occurs in the egg or sperm cell. In such situations, the disorder is not inherited from the parents.

Figure 1. Paramyotonia congenita autosomal dominant inheritance pattern

Paramyotonia congenita autosomal dominant inheritance pattern

People with specific questions about genetic risks or genetic testing for themselves or family members should speak with a genetics professional.

Resources for locating a genetics professional in your community are available online:

Paramyotonia congenita symptoms

Paramyotonia congenita typically begins in infancy or early childhood. Affected individuals experience spells of muscle stiffness or when the muscles do not relax after contracting (myotonia). Muscle stiffness in paramyotonia congenita is the inability for the muscles to relax in a timely manner after contracting (myotonia). The stiffness of the muscles can get worse with repeated movements. The muscles most commonly affected are located in the neck, face, arms and hands, although it can affect the muscles used for breathing and swallowing, as well as muscles in the lower back 15). Paramyotonia congenita is usually apparent during infancy and always presents by teenage years. Symptoms do not progress with age. Individuals with paramyotonia congenita do not have wasting of muscles (atrophy) but often have an increase of muscle bulk (hypertrophy).

Symptoms can be triggered by exposure to the cold or after physical activity. There are also intermittent periods of a type of muscle weakness in which there is no muscle tone (flaccid paresis).

The severity of the muscle stiffness depends on the individual; some patients experience painful myotonia, while others experience painless myotonia.

Paramyotonia congenita diagnosis

When paramyotonia congenita is suspected, a test is administered to test the capacity of muscles to conduct electricity (electromyography). During the test, the muscles are chilled and electrical signals are recorded before and after the muscle is cooled. The electromyography (EMG) will show rapid repetitive electrical discharges. EMG cannot always diagnose paramyotonia congenita definitively, and further testing may be necessary.

Genetic testing on a blood sample will result in a definitive diagnosis by showing the presence of a characteristic mutation in the SCN4A gene.

Paramyotonia congenita treatment

The treatment of paramyotonia congenita is based on the individual’s symptoms; paramyotonia congenita can be handled on a day-to-day basis and many patients can lead normal lives. Individuals must be cautious to sudden exposures to very cold weather, as well as avoiding sudden heavy physical activity.

Muscle stiffness could also be triggered or enhanced by potassium-rich foods. Patients will need to learn how to manage their potassium-intake. They should avoid potassium-rich foods, avoid skipping meals and take carbohydrate rich snacks in between meals.

The aim of treatment is to reduce the intensity of acute symptoms and to prevent, as far as possible, further attacks. Some attacks are so mild that treatment is not necessary. However, in other instances drug therapy is required.

Treatment with medications that block the sodium channels such as mexiletine and lamotrigine may help reduce the stiffness related to myotonia. Some patients with paramyotonia congenita may benefit from acetazolamide or thiazide diuretic drugs to reduce the number of paralytic attacks.

Genetic counseling is recommended for patients and their families.

Paramyotonia congenita prognosis

Paramyotonia congenita is a non-progressive disease. Episodes of myotonia (inability to relax muscles at will) begin in infancy. Episodes of weakness generally begin in adolescence, if they occur at all. Some older people with paramyotonia congenita develop permanent muscle weakness that can be disabling.

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