Mild Clinical Features and Histopathologically Atypical Cores in Two Korean Families with Central Core Disease Harboring RYR1 Mutations at the C-Terminal Region

BACKGROUND: Central core disease (CCD) is a congenital myopathy characterized by distinctive cores in muscle fibers. Mutations in the gene encoding ryanodine receptor 1 (RYR1) have been identified in most CCD patients. CASE REPORT: Two unrelated patients presented with slowly progressive or nonprogressive proximal muscle weakness since childhood. Their family history revealed some members with the same clinical problem. Histological analysis of muscle biopsy samples revealed numerous peripheral cores in the muscle fibers. RYR1 sequence analysis disclosed a novel mutation in exon 101 (c.14590T>C) and confirmed a previously reported mutation in exon 102 (c.14678G>A). CONCLUSIONS: We report herein two families with CCD in whom missense mutations at the C-terminal of RYR1 were identified. Although it has been accepted that such mutations are usually associated with a severe clinical phenotype and clearly demarcated central cores, our patients exhibited a mild clinical phenotype without facial muscle involvement and skeletal deformities, and atypical cores in their muscle biopsy specimens.

Characteristic Muscle Involvement on Magnetic Resonance Imaging in Central Core Disease

Central core disease (CCD) is a rare congenital myopathy characterized by central cores on muscle biopsy. We present three familial cases of CCD. The muscle pathology manifested as a predominance of type 1 muscle fibers and highly oxidative fibers with central cores. Muscle MRI showed selective involvement of the sartorius, vastus lateralis, and adductor magnus muscles. We suggest that muscle MRI can be used as an additional tool in the diagnosis of CCD.

A Double Mutation of the Ryanodine Receptor Type 1 Gene in a Malignant Hyperthermia Family with Multiminicore Myopathy

BACKGROUND AND PURPOSE: At least 100 Ryanodine receptor type 1 (RYR1) mutations associated with malignant hyperthermia (MH) and central core disease (CCD) have been identified, but 2 RYR1 mutations accompanying multiminicore myopathy in an MH and/or CCD family have been reported only rarely. METHODS: Fifty-three members of a large MH family were investigated with clinical, histopathologic, RYR1 mutation, and haplotyping studies. Blood creatine kinase (CK) and myoglobin levels were also measured where possible. RESULTS: Sequencing of the entire RYR1 coding region identified a double RYR1 mutation (R2435H and A4295V) in MH/CCD regions 2 and 3. Haplotyping analysis revealed that the two missense heterozygous mutations (c.7304G>A and c.12891C>T) were always present on a common haplotype allele, and were closely cosegregated with histological multiminicores and elevated serum CK. All the subjects with the double mutation showed elevated serum CK and myoglobin, and the obtained muscle biopsy samples showed multiminicore lesions, but only two family members presented a late-onset, slowly progressive myopathy. CONCLUSIONS: We found multiminicore myopathy with clinical and histological variability in a large MH family with an unusual double RYR1 mutation, including a typical CCD-causing known mutant. These results suggest that multiminicore lesions are associated with the presence of more than two mutations in the RYR1 gene.

Casos clinicos: miopatía congénita de núcleos centrales / Clinical case: congenital myopathy central core

Las miopatías congénitas son enfermedades hereditarias que generalmente presentan curso benigno. Se caracterizan por su variada presentación fenotípica que dificulta su diagnóstico.

Multi-minicore disease: a rare form of myopathy.

BACKGROUND: Multi-minicore disease is a rare form of myopathy characterized by slowly progressive or nonprogressive muscle weakness and characteristic multiple cores within the muscle fibers. To the best of our knowledge, this is first documentation of the clinicopathological features of this rare entity from India. MATERIALS AND METHODS: A ll cases of multi-minicore disease diagnosed in our laboratory were retrieved. Clinical and pathological features were reviewed. RESULT: During a period of two years (January 2004 to December 2005), we received 985 muscle biopsies for various reasons. Of which, 15 were diagnosed as myopathies and four of which were of multi-minicore disease. Thus, multi-minicore disease comprises 0.40% of all muscle diseases and 26.6% of all myopathies. All were male and presented in early childhood (first decade of life) with generalized hypotonia and muscle weakness. All of them had dysmorphic facies and three had high arched palate. CPK levels were normal and EMG was myopathic except in one patient. Microscopic examination revealed minimal changes with Type I fibers' predominance but characteristic multiple cores in the myofibers. Ultrastructural examination showed both structured and unstructured cores. CONCLUSIONS: Multi-minicore disease, although a rare form of myopathies, should be suspected in children who present with generalized hypotonia and slowly progressive muscle weakness along with dysmorphic facies.

Central core disease.

Central core disease is a congenital myopathy characterized by generalized hypotonia, muscle weakness and presence of central cores on muscle biopsy. It generally presents during infancy. It is familial with autosomal dominant inheritance [Chromosome 19q13.1; Gene Locus RyR1 (Ryanodine receptor gene)]. We report here two cases of central core disease in a 3-year-old male child and 8 year old female child.

Central Core Disease: A Case Report

Central core disease is a rare autosomal dominantly inherited non-progressive congenital myopathy, which is pathologically characterized by the formation of a "core". We report a 28-year-old female with non-progressive muscle weakness, who had a hypotonic posture at birth. The developmental milestones were delayed with her first walking at 18 months of age. She could not run or walk a long distance and weight-bearing tasks were almost impossible. None of her family members showed motor symptoms. An investigation of the electromyography and nerve conduction velocity showed non-specific results. A gastrocnemius muscle biopsy revealed central cores in approximately 70% of myofibers with a type 1 myofiber predominance and deranged sarcolemmal structures. To the best of our knowledge, this is the fifth report of central core disease in the Korean literature.

Ankylosing spondylitis and central core disease: case report

Ankylosing spondylitis (AS) is an inflammatory disorder of unknown cause that primarily affects the axial skeleton. Neurological manifestations of AS are usually related to spinal deformities. Previous studies of the paraspinal muscles of AS patients showed muscle fiber atrophy, and core fibers. On the other hand, central core disease (CCD) is a genetic condition that primarily involves the skeletal muscles, but can present articular deformities secondary to muscular weakness. We report the case of a 45-year-old man with clinical and radiological diagnosis of AS and proximal muscular weakness in the lower limbs. Needle electromyography showed myopathic features and nerve conduction study was normal. Muscle biopsy disclosed almost complete predominance of type-1 fibers, and fibers with central cores. This is the first report of AS and CCD. Whether central core myopathy is coincidental or a new association with AS is discussed

Results of Subcutaneous Lengthening with Smooth CD Rod in Young Children with Scoliosis before Growth Spurt / 대한정형외과학회잡지

For young children with scoliosis before growth spurt, suhcutaneous lengthening without fusion was designed by Harrington and modified by Moe and Luque. However, many problems including spontaneous fusion, rod breakage, and hook disloclgement have been ohserved. CotrelDubousset(CD) instrumentation was sometimes used, but it usually resulted in failure due to soft tissue adhesion around the rough surface of ordinary CD rod. We tried to use the smooth CD rod, transvcrse-pedicle clawing on the upper part, and pedicle screw inscrtion on upper and lower part of the curve to reduce the hardware failures. Among 8 patients in whom suhcutaneous lengthening with smooth CD rod was carried out hetween October l992 and Suly 1996. 4 cases perfomed with final spinal fusion were analysed. There were I central core disease, 1 multicore disease and 2 idiopathic scoliosis(infantile and juvenile type). Mean age at the first operation was l0.0(8.8-11.8) years, and the Risser sign was all grade 0 except one with grade 1. Suhcutaneous lengthening was performed every 5 or 6 months Mean lengthening duration was 22(9-39) months and mean age at spinal fusion was 11.7(9.6-13.8) years. Mean Cobb angle decreased from 7ldegrees (55degrees-88degrees) at preoperative stage to 32 (10degrees-59degrees) at the last follow-up. There were 5 complications during 21 operations, and three hardware failures comprised 2 hook dislodgcment and 1 screw pull-out. Crankshaft phenomenon happened in I case who had had a posterior fusion in young age(9.6 years) due to laminar fracture. The suhcutaneous lengthening with smooth CD rod can he another option of treatment for young children with severe scoliosis. prescrving the powth potential of involved vertebrae with few complications.

Three cases of central core disease / 대한소아신경학회지

No abstract available.