Nemaline Rod Myopathy

Rare, congenital, slowly progressive inherited neuromuscular disease that usually is apparent at birth; characterized by extreme hypotonia.

Nemaline Myopathy.

Nemaline myopathy has been classified into four major subtypes:

Severe neonatal form: Characterized by severe muscle hypotonia with little spontaneous movements, severe dysphagia and absence of sucking ability, and respiratory problems that are considered life-threatening during the first weeks or months of life. A fetal form (“fetal akinesia sequence") has been suggested but is still considered part of this entity. It is associated with large quantity of amniotic fluid, abnormal muscle growth, and underdevelopment of the lung.

Mild congenital or “classic" form: Age at onset between birth and the first years of life. It is characterized by extreme muscle weakness, feeding difficulties, delayed motor development (e.g., walking difficulties, speech abnormalities), and respiratory complications that are not considered as severe at the neonatal form. The evolution of the disease is often static or very slowly progressive. Most affected individuals can have an active life; others may experience deterioration during the period of rapid growth before puberty.

Childhood-onset form: Age at onset between 10 and 20 years. The apparition of muscle weakness is slowly progressive and allows motor development to be considered normal. The clinical symptoms typically progress during childhood, but exercises that increase muscle development and strength may offset the progression of the disease.

Late-onset or adult-onset form: Characterized by the absence of family history or symptomatology before the apparition of the muscle weakness, which is mostly apparent in the extremities and the trunk.

Affects females more than males; estimated incidence is 2:10,000 live births.

Two clinically indistinguishable types are described. Type I is autosomal dominant with incomplete penetrance and is caused by a defect in the gene TPM3 (or NEM1) located on chromosome 1q21-q23 and encoding for tropomyosin-3. Type II is autosomal recessive and is caused by a mutation of the gene NEM2 located on chromosome 2q21.2-q22 and encoding for nebulin.

All muscles, including the diaphragm, may be affected. The disease is nonprogressive or slowly progressive. Cardiac involvement is rare, but cases of cardiomyopathy in adults have been described.

Serum creatine kinase levels are usually, but not always, normal. Muscle biopsy shows disproportion of type I muscles fibers and subsarcolemmal rod-like structures made of excessive Z-band material.

In the neonatal period, hypotonia and muscle weakness produce swallowing problems and weak cry; severe cases progressing rapidly to respiratory failure are described. Motor development (walking) is delayed. Muscle mass is thin; truncal and proximal muscles are most affected, but distal limb, pharyngeal, and facial muscles can be involved. The face is usually long with a high-arched palate, malocclusion, prognathism, or micrognathia. Abnormal gait. Normal intelligence. Scoliosis and intercostal muscle weakness produce severe restrictive lung disease. Congenital heart disease or cardiomyopathy may be rarely present.

Check pulmonary function: ability to cough, pulmonary function if the patient is old enough to cooperate. Pulse oximetry while breathing room air should be obtained. Nocturnal oximetry can be useful because hypoxemia during sleep caused by diaphragmatic fatigue has been described. Echocardiography to exclude congenital heart diseases or cardiomyopathy must be performed.

Malignant hyperthermia has not been reported in patients with nemaline myopathy. The narrow face with malocclusion and micrognathia can make direct laryngoscopy and tracheal intubation difficult. Patients are at risk for postoperative complications. The use of postoperative mechanical ventilation may be indicated to allow good analgesia and chest physiotherapy.

Although some resistance to succinylcholine and a normal response to pancuronium have been observed in one case, it probably is safer to avoid succinylcholine as in any myopathy; if muscle relaxation is necessary, use a short-acting muscle relaxant while assessing the patient's response with neuromuscular monitoring.

Central Core Disease: Rare inherited neuromuscular disorder that is milder and less progressive than nemaline myopathy. Characterized by hypotonia, especially of the arms and legs. Symptoms begin during the first year of life. Infants with central core disease may have difficulty learning to sit and walk. Other features include joint hypermobility and scoliosis.

Werdnig-Hoffman Disease: Rare, inherited, childhood neuromuscular disorder characterized by degenerative changes in the spinal cord. Early symptoms include generalized muscle hypotonia, hypermobility of joints, and absent tendon reflexes. Other features include dysphagia and problems with breathing and the kidneys.

Myotubular Myopathy: Rare muscle-wasting disorder that occurs in three forms. The most severe form is present at birth and presents with severe respiratory muscle weakness. A less severe form is present at birth or early childhood and progresses slowly. The least severe form presents between the first and third decades of life and is slowly progressive. Clinically, weakness of the upper eyelid, jaw, tongue, lips, mouth, throat, and neck may be present. Scoliosis becomes apparent in adolescence. Seizures may be present.

Limb-Girdle Muscular Dystrophy (LGMD): Rare inherited muscular disorder that may begin at birth or during adulthood. Infants present with generalized muscle weakness, poor sucking ability, and dysphagia. Other features include a high-arched palate, thin face, ptosis, and scoliosis. Adults have a clumsy walk and general hypotonia of the hips and shoulders.

Congenital Myopathy with Fiber-Type Disproportion: Rare inherited muscle disease that affects the growth of type I muscle fibers. Newborn infants usually have generalized hypotonia. Other features include scoliosis, dislocated hip joints, foot deformities, and a high-arched palate. Symptoms tend to improve with age.

Benign Congenital Hypotonia: Nonprogressive neuromuscular disorder present at birth; characterized by a generalized muscle weakness or “floppiness” (hypotonia). Infants appear weak and listless.

Batten Turner Type Congenital Myopathy: Extremely rare inherited muscle disorder characterized by lack of muscle tone or severe hypotonia (floppiness) at birth. Slowly progressive during infancy and childhood; this disorder is not progressive in adulthood.

Canavan Syndrome: Rare inherited disorder characterized by progressive degeneration of the central nervous system, appearing in infancy. Early symptoms include a general lack of energy, floppiness, and loss of previously acquired motor skills. Other features include seizure-like movement of the arms and legs, poor head control, and deafness.