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Table of Contents    
Year : 2015  |  Volume : 63  |  Issue : 6  |  Page : 985-986

RYR1-associated core myopathy

1 Department of Neonatal, Pediatric and Adolescent Medicine, Division of Pediatric Neurology, BL Kapur Super Specialty Hospital, New  Delhi, India
2 Department of Neonatal, Pediatric and Adolescent Medicine, BL Kapur Super Specialty Hospital, New  Delhi, India

Date of Web Publication20-Nov-2015

Correspondence Address:
Puneet Jain
Department of Neonatal, Pediatric and Adolescent Medicine, Division of Pediatric Neurology, BL Kapur Super Specialty Hospital, New  Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.170098

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How to cite this article:
Jain P, Mahajan S. RYR1-associated core myopathy. Neurol India 2015;63:985-6

How to cite this URL:
Jain P, Mahajan S. RYR1-associated core myopathy. Neurol India [serial online] 2015 [cited 2022 May 25];63:985-6. Available from: https://www.neurologyindia.com/text.asp?2015/63/6/985/170098


An 18-month-old boy, a resident of Oman, presented with delayed milestones. He was born to a nonconsanguineous couple. There was an uneventful perinatal period. There was no history of increased liquor amni or decreased antenatal fetal movements. He achieved head-holding at 9-months of age and could sit unsupported at the time of admission. He could speak a few bisyllables. He had no seizures, hearing or visual impairment, feeding difficulties, choking episodes, or respiratory problems. His family history was unremarkable. He was operated for a right sided congenital hip dislocation at 12-months of age.

Examination revealed an age-appropriate-anthropometry, no facial dysmorphism or neurocutaneous features, and a normal spinal examination. He had global hypotonia, depressed muscle stretch reflexes, and poor antigravity movements in distal limbs. There was no facial weakness, and gag reflex was preserved. He also had fixed contractures at the elbow and ankle joints, but had no distal laxity or tongue fasciculations. He had a lower limb length asymmetry with a shorter right lower limb.

He had a normal calcium profile, thyroid function tests, and serum creatine kinase (68.5 U/L). His echocardiography was normal. Nerve conduction studies revealed low amplitude compound muscle action potential amplitude in tibial and common peroneal nerves with preserved distal latencies and conduction velocities. Limited electromyography showed no spontaneous activity with myopathic motor unit action potentials. Electrophysiological studies were suggestive of a muscle disorder. Targeted sequencing analysis of congenital myopathy genes revealed a novel heterozygous 3-base-pair deletion in exon-35 of the RYR1 gene (Glu1876del). This variation was not detected in either of the parents. The final diagnosis of RYR1-positive central core disease was made (de novo mutation).

The child was initiated with physical rehabilitation, and genetic counseling was performed.

Core myopathies are a heterogeneous group of congenital myopathies with a common characteristic histopathological feature on muscle biopsy.[1],[2] RYR1 (skeletal muscle ryanodine) gene mutations are the most common cause. The classical phenotypic features include onset in early childhood, motor delay, global hypotonia, relative sparing of facial muscles, myalgias, orthopedic complications (congenital dislocation of hip, scoliosis, foot-deformities, and contractures), and susceptibility towards developing malignant hyperthermia. They have a static or slowly progressive course with most children achieving the ability to walk. Serum creatine kinase (CK) is usually normal. Treatment is mainly supportive and multi-disciplinary.

The presence of peripheral hypotonia, facial sparing, congenital dislocation of hip, contractures, and normal serum creatine kinase levels favored the diagnosis of central core disease in the reported case. This was subsequently confirmed by the genetic testing. An invasive test such as a muscle biopsy was avoided as the parents were able to afford the genetic testing. Common differential diagnosis included congenital muscular dystrophies (facial sparing, usually elevated CK, and dystrophic muscle biopsy), spino-muscular-atrophy (facial sparing, tongue-fasciculations), congenital myasthenic syndrome (facial weakness, ptosis, ophthalmoparesis, and bulbar weakness), and metabolic myopathies (organomegaly, acidosis, and hyperammonemia).[3],[4] Certain clinical clues that may help in differentiating various subtypes of congenital myopathies are summarized in [Table 1]. Clinical clues and features on muscle biopsy may help in guiding the genetic testing.
Table  1: Clinical clues for differentiating various subtypes of congenital myopathies

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 » Acknowledgments Top

The authors are grateful to MedGenome Labs Pvt. Ltd., (Bengaluru, India) for performing the genetic testing.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 » References Top

Jungbluth H, Sewry CA, Muntoni F. Core myopathies. Semin Pediatr Neurol 2011;18:239-49.  Back to cited text no. 1
Snoeck M, van Engelen BG, Küsters B, Lammens M, Meijer R, Molenaar JP, et al. RYR1-related myopathies: A wide spectrum of phenotypes throughout life. Eur J Neurol 2015;22:1094-112.  Back to cited text no. 2
North KN, Wang CH, Clarke N, Jungbluth H, Vainzof M, Dowling JJ, et al. Approach to the diagnosis of congenital myopathies. Neuromuscul Disord 2014;24:97-116.  Back to cited text no. 3
North KN. Clinical approach to the diagnosis of congenital myopathies. Semin Pediatr Neurol 2011;18:216-20.  Back to cited text no. 4


  [Table 1]

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