SNP Shot: Genomic Insights

Centronuclear myopathy is a condition characterized by muscle weakness (myopathy) and muscle wasting (atrophy) affecting the skeletal muscles, which are responsible for movement. The severity of this condition varies significantly among individuals, even within the same family.

The onset of muscle weakness in individuals with centronuclear myopathy can range from birth to early adulthood. This weakness typically worsens gradually, potentially leading to delays in motor skill development like crawling or walking, muscle pain during exercise, and difficulty with ambulation. Some individuals may require wheelchair assistance as muscle atrophy and weakness progress. In rare cases, muscle strength may improve over time.

Some individuals with centronuclear myopathy may experience mild to severe breathing difficulties due to weakness in the respiratory muscles. Other common features include droopy eyelids (ptosis) and weakness in other facial muscles, including those controlling eye movement. Foot abnormalities, a high-arched palate, and scoliosis (an abnormal curvature of the spine) may also be present. Less frequently, affected individuals may develop a weakened heart muscle (cardiomyopathy), nerve dysfunction (neuropathy), or intellectual disability.

A defining characteristic of centronuclear myopathy is the abnormal positioning of the nucleus within muscle cells, visible under a microscope. Typically, the nucleus resides at the edge of these elongated muscle cells. However, in individuals with this condition, the nucleus is found centrally located. The impact of this altered nuclear position on muscle cell function remains unclear.

Inheritance:

When mutations in the DNM2 gene are the cause, centronuclear myopathy follows an autosomal dominant inheritance pattern. This means that inheriting only one copy of the mutated DNM2 gene in each cell is sufficient to cause the disorder. In rare instances, autosomal dominant BIN1 gene mutations can also cause centronuclear myopathy. Centronuclear myopathy resulting from TTN gene mutations, and most cases caused by BIN1 gene mutations, are inherited in an autosomal recessive manner. This requires inheriting two copies of the mutated gene (one from each parent) in each cell. Parents who carry only one copy of the mutated gene are typically asymptomatic carriers. Cases of centronuclear myopathy not linked to these specific genes typically exhibit autosomal recessive inheritance, though autosomal dominant inheritance can occur.