Nemaline myopathy

Signs and symptoms

Signs vary widely among individuals. In young children and newborns, common features include lack of movement, difficulty eating and breathing, a swollen face in disproportional areas, swaying, and feeble muscles in the neck and upper rib cage. Delayed motor development is typical, and many children take longer than average to start walking. Facial muscle involvement often leads to an elongated face and a lower mandible.

Weakness tends to be more severe in proximal muscles than distal ones, while ocular muscles are usually spared. Respiratory problems are a primary concern across all forms, and respiratory infections are common. Scoliosis frequently develops in childhood and worsens during puberty, often requiring spinal fusion surgery. Joint deformities and scoliosis become more common with age.

Gastroesophageal reflux is associated with NM, though not common, and heart abnormalities can occur but are unlikely. Most children with mild NM eventually walk independently, though later than peers; those with severe NM generally have limited limb movement and use wheelchairs full-time. Muscle exhaustion often begins between ages 20 and 50, and NM is usually not progressive.

Causes

Nemaline myopathy results from changes in any of at least 11 genes, making it both clinically and genetically diverse. It can be inherited in either an autosomal dominant or autosomal recessive pattern. The most common mutations occur in the NEB gene, accounting for roughly half of all cases, typically with symptoms appearing at birth or in early childhood and following an autosomal recessive inheritance. The ACTA1 gene is involved in 15 to 25 percent of cases, sometimes through autosomal dominant inheritance and often due to spontaneous new mutations.

MYPN is the most recently discovered associated gene. Diagnosis relies on clinical features like muscle weakness, reduced or absent reflexes, and a high-arched palate, plus the microscopic presence of nemaline rods in muscle tissue and genetic testing. A person’s physical abilities do not closely match their specific gene mutation or the appearance of their muscle biopsy. The condition affects males and females equally.

Mechanism

In nemaline myopathy, muscle contraction is adversely affected. At the electron microscopic level, rod-shaped components (nemaline bodies) are often seen in some muscle cells and are diagnostic, but their presence does not cause muscle weakness; they appear as a result of dysfunction within the muscle fiber. There is no connection between the number of rods and the degree of weakness. All known gene mutations encode components of the sarcomere, and evidence suggests that some forms of NM disrupt the arrangement of muscle fibers, reducing contraction efficiency.

Respiratory muscles are often more affected than other skeletal muscles, while cardiac muscle is usually unaffected (though dilated cardiomyopathy can occur in some cases) and ocular muscles are typically spared. The first identified form, due to mutations in the slow α-tropomyosin gene TPM3, varies in severity and tends to affect lower limbs more than upper limbs.

Treatment

There is no cure for nemaline myopathy. Treatments focus on minimizing symptoms and vary with disease severity.

Accommodations may include braces or other stabilizers, moderate stretching, and moderate exercise to help maintain muscle health. Regular care from a neurologist, physical therapist, speech therapist, and psychologist is recommended to support the patient and family. Low-intensity exercise has shown improvements in muscle function, while vigorous exercise and heavy weights should be avoided.

Did You Know?

• Electromyography (EMG) can determine if nerve or muscle cells are damaged in NM.
• Needle biopsy can confirm the presence of rod-like structures in muscle cells.
• Supplemental L-tyrosine has been associated with mild improvements in secretion handling, energy level, and physical functioning in some people with NM.