congenital multicore myopathy with external ophthalmoplegia

Congenital multicore myopathy with external ophthalmoplegia is a neuromuscular disorder that primarily affects skeletal muscles and is characterized by muscle weakness, neonatal hypotonia, and delayed motor development. The condition is caused by pathogenic variants in the RYR1 gene, which encodes ryanodine receptor 1, a protein essential for calcium release and proper muscle contraction. It typically presents in infancy with symptoms such as respiratory insufficiency and muscle atrophy. As precise prevalence estimates are not established for this condition, it is best described as uncommon.

Individuals with congenital multicore myopathy with external ophthalmoplegia almost always exhibit neonatal hypotonia, delayed motor milestones, and generalized muscle weakness. Characteristic clinical features include respiratory insufficiency, the presence of minicore lesions on muscle biopsy, skeletal muscle atrophy, and centrally nucleated muscle fibers. Additional findings, such as increased variability in muscle fiber diameter, decreased fetal movement, and feeding difficulties in infancy, are observed in a subset of cases. Not all individuals experience all these features, and the severity can vary considerably.

This condition is caused by pathogenic variants in the RYR1 gene, which is responsible for encoding the ryanodine receptor 1, an essential component in muscle excitation and contraction. The disruption in this receptor impairs calcium release, leading to the clinical manifestations observed in affected individuals. It is inherited in an autosomal recessive pattern, meaning that an affected person inherits two altered copies of the gene, one from each parent. Genetic counseling is recommended to help families understand recurrence risks and assist with family planning.

Currently, management focuses on supportive care and symptom management since there are no foundational therapies or FDA-approved treatments available for this condition. Treatment is tailored to the individual and generally involves a multidisciplinary team, including specialists in neuromuscular care. Supportive interventions may include physical therapy, respiratory support, and nutritional management, while regular surveillance is an essential part of long-term care to identify emerging complications early. Genetic counseling is also recommended to provide further guidance regarding inheritance and family planning.

The clinical course of congenital multicore myopathy with external ophthalmoplegia is variable and largely depends on the severity of symptoms, age at diagnosis, and access to specialized care. With current standards of care and a multidisciplinary approach, many individuals experience an improved quality of life and stabilization of symptoms over time. Outcomes described in medical literature continue to evolve as standards of care improve, and while the condition requires lifelong management, early intervention and regular monitoring can help mitigate complications. Families are encouraged to connect with specialists familiar with this condition as part of ongoing care.

Several clinical trials are currently underway exploring new treatment approaches for congenital multicore myopathy with external ophthalmoplegia. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team regarding eligibility.