autosomal dominant centronuclear myopathy

Autosomal dominant centronuclear myopathy (AD-CNM) is a hereditary muscle disorder in which skeletal muscle fibers show nuclei clustered in the center rather than at the periphery. Variants in the DNM2 gene disrupt normal muscle fiber organization and lead to weakness that often begins in childhood or early adulthood. Both males and females can be affected, and symptoms may range from very mild to more noticeable difficulties with everyday activities. Precise prevalence figures have not been established, but the condition is considered uncommon. Severity and symptoms vary widely between individuals.

Early signs usually include low muscle tone (hypotonia) and weakness of the muscles closest to the trunk, such as those of the shoulders, hips, and neck. Some people notice drooping eyelids (ptosis) or limited eye movement, which can prompt medical evaluation. Electromyography often reveals myotonic discharges and muscle fibrillations, while blood tests may show mildly elevated creatine kinase levels. Over time many individuals develop additional muscle weakness that can extend to the hands and lower legs, occasionally leading to difficulties with fine motor tasks, climbing stairs, or prolonged walking. Contractures of the Achilles tendon and a curved lower spine (lumbar hyperlordosis) are reported in a subset, and rare individuals lose the ability to walk. Facial muscle weakness and areflexia (reduced reflexes) may also appear. Not all individuals experience all features, and severity can range from minimal limitations to noticeable functional impairment. Because the clinical picture can evolve, ongoing monitoring helps track changes and guide therapy.

AD-CNM is caused by pathogenic variants in the DNM2 gene, which provides instructions for the protein dynamin 2. Dynamin 2 is involved in membrane remodeling inside muscle cells; when it does not work properly, the internal structure of muscle fibers is altered, and their nuclei remain centrally located. The condition follows an autosomal dominant inheritance pattern, meaning one altered copy of DNM2 is sufficient to cause disease. An affected individual has a 50 percent chance of passing the variant to each child. Even within the same family, the specific symptoms and degree of weakness can differ markedly (variable expressivity), so genetic counseling is recommended for relatives who may be at risk.

Currently, management focuses on supportive care and symptom relief. A multidisciplinary care team—often including neuromuscular specialists, physiatrists, physical and occupational therapists, and orthopedic professionals—creates an individualized plan. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Common elements include physiotherapy to maintain strength and flexibility, bracing or orthopedic intervention for contractures, and evaluation for respiratory or swallowing difficulties if they arise. In addition to treating active symptoms, ongoing monitoring of mobility, joint range of motion, and spinal alignment guides timely interventions. Because research into targeted therapies is ongoing, patients should discuss emerging options and potential study participation with their healthcare team. Genetic counseling is advised for affected individuals and their families.

Most people with AD-CNM experience a relatively stable or slowly progressive course, and many remain able to walk and lead active adult lives with appropriate therapy and support. However, the condition’s impact varies; some individuals have only mild limitations, while others develop more significant weakness or require mobility aids. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with neuromuscular specialists familiar with this condition and to seek genetic counseling for planning and support.