Central Core Disease – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY

NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.

Clinical characteristics: Central core disease (CCD) is characterized by muscle weakness ranging from mild to severe. Most affected individuals have mild disease with symmetric proximal muscle weakness and variable involvement of facial and neck muscles. The extraocular muscles are often spared. Motor development is usually delayed, but in general, most affected individuals acquire independent ambulation. Life span is usually normal. Severe disease is early in onset with profound hypotonia often accompanied by poor fetal movement, spinal deformities, hip dislocation, joint contractures, poor suck, and respiratory insufficiency requiring assisted ventilation. The outcome ranges from death in infancy to survival beyond age five years. The weakness in CCD is not typically progressive.

Diagnosis/testing: The diagnosis of CCD is based on clinical findings of muscle weakness, the histopathologic findings of characteristic cores on muscle biopsy, and molecular genetic testing. Most CCD is associated with pathogenic variants in RYR1, the gene encoding the ryanodine receptor 1.

Management: Treatment of manifestations: Physical therapy for hypotonia and weakness that may include stretching and mild to moderate low-impact exercise; assistive devices as needed for ambulation; orthopedic surgery as needed for scoliosis, congenital hip dislocation, foot deformities; respiratory support, breathing exercises, chest physiotherapy as needed; dietary supplementation and nasogastric or gastrostomy feeding as needed.

Prevention of secondary complications: Intervention as needed to prevent respiratory compromise from scoliosis; immunization against influenza; prompt treatment of respiratory infection; mobility and physical therapy to prevent joint contractures.

Surveillance: Routine assessment of spine for scoliosis, joints for contractures, respiratory parameters (e.g., respiratory rate, peak expiratory flow rate [PEFR], forced vital capacity [FVC], and forced expiratory volume in one second [FEV1]), motor abilities to determine need for physical therapy, occupational therapy, assistive devices; sleep studies when signs of nocturnal hypoxia are present.

Agents/circumstances to avoid: Although the actual risk for malignant hyperthermia susceptibility is unknown, it is prudent for individuals with CCD to avoid inhalational anesthetics and succinylcholine.

Evaluation of relatives at risk: If the RYR1 pathogenic variant is known, it is appropriate to offer at-risk relatives molecular genetic testing to identify those with possible increased malignant hyperthermia susceptibility.

Genetic counseling: Central core disease (CCD) is usually inherited in an autosomal dominant (AD) manner but can be inherited in an autosomal recessive (AR) manner. Most individuals diagnosed with AD central core disease have an affected parent or an asymptomatic parent who has a pathogenic variant. The proportion of AD CCD caused by de novo pathogenic variants is unknown. Each child of an individual with AD CCD has a 50% chance of inheriting the pathogenic variant. The parents of a child with AR CCD are obligate heterozygotes and therefore carry one mutated allele. Heterozygotes (carriers) are often asymptomatic. At conception, each sib of an individual with AR CCD has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Prenatal diagnosis for pregnancies at increased risk for AD or AR CCD is possible once the pathogenic variant(s) have been identified in an affected family member.