congenital myopathy with internal nuclei and atypical cores

Congenital myopathy with internal nuclei and atypical cores is a genetic skeletal muscle disorder characterized by neonatal hypotonia, distal greater than proximal muscle weakness, and progressive exercise intolerance accompanied by myalgias. Affected individuals typically display mild-to-moderate motor impairment with preserved ambulation along with mild cognitive impairment in many cases. The condition is linked to pathogenic variants in the CCDC78 gene and is inherited in an autosomal dominant manner. It is very rare, affecting fewer than 1 in 1 million people.

The clinical presentation is primarily neuromuscular, with persistent muscle weakness noted in all affected individuals and exercise intolerance present in a high percentage of cases. Patients may experience myalgias, frequent falls, and motor delays, which are commonly observed as early signs. Additionally, a subset of individuals display mild cognitive impairment and occasional seizures. Not all individuals experience all features, and severity varies considerably.

This condition results from pathogenic variants in the CCDC78 gene, which plays a vital role in maintaining normal skeletal muscle structure and function. It is inherited in an autosomal dominant pattern, meaning that a single altered copy of the gene can lead to the disorder. Because the condition can be passed from an affected parent to a child, genetic counseling is recommended for families considering future pregnancies.

Currently, management focuses on supportive care and symptom management as there are no treatments specifically approved for this condition. Treatment is tailored to each individual and typically involves a multidisciplinary team to address neuromuscular health and cognitive concerns. Regular surveillance and monitoring of motor function, along with physical and occupational therapy, are key components of care. Patients and their families are encouraged to discuss treatment options and symptom management strategies with their healthcare team, and genetic counseling is recommended to assist in family planning.

The long‐term outlook for individuals with congenital myopathy with internal nuclei and atypical cores varies widely. Many patients continue to maintain ambulation and a good quality of life, although motor challenges and mild cognitive issues may persist. Outcomes described in medical literature continue to evolve as standards of care improve, and individual trajectories differ depending on the severity of symptoms and access to multidisciplinary care. Families often find it helpful to connect with genetic counselors and specialists to navigate care and future planning.