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Central core disease(CCD)

MedGen UID:
199773
Concept ID:
C0751951
Disease or Syndrome
Synonyms: CCD; Central core disease of muscle; Muscle core disease; Muscular central core disease; Myopathy, Central Core; Myopathy, central fibrillar; Shy-Magee syndrome
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Central core myopathy (43152001); Central core disease (43152001)
 
Gene (location): RYR1 (19q13.2)
OMIM®: 117000
Orphanet: ORPHA597

Definition

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. [from GTR]

Additional descriptions

From GeneReviews
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.  https://www.ncbi.nlm.nih.gov/books/NBK1391
From OMIM
Typical central core disease is a relatively mild congenital myopathy, usually characterized by motor developmental delay and signs of mild proximal weakness most pronounced in the hip girdle musculature. Orthopedic complications, particularly congenital dislocation of the hips and scoliosis, are common, and CCD patients are at risk of having malignant hyperthermia (MHS1; 145600). Onset of CCD is usually in childhood, although adult onset has also been reported, illustrating phenotypic variability (Jungbluth et al., 2009). Some patients can present in utero or at birth with severe congenital myopathy (Bharucha-Goebel et al., 2013).  http://www.omim.org/entry/117000
From GHR
Central core disease is a disorder that affects muscles used for movement (skeletal muscles). This condition causes muscle weakness that ranges from almost unnoticeable to very severe.Most people with central core disease experience persistent, mild muscle weakness that does not worsen with time. This weakness affects the muscles near the center of the body (proximal muscles), particularly muscles in the upper legs and hips. Muscle weakness causes affected infants to appear "floppy" and can delay the development of motor skills such as sitting, standing, and walking. In severe cases, affected infants experience profoundly weak muscle tone (hypotonia) and serious or life-threatening breathing problems. Central core disease is also associated with skeletal abnormalities such as abnormal curvature of the spine (scoliosis), hip dislocation, and joint deformities called contractures that restrict the movement of certain joints.Many people with central core disease also have an increased risk of developing a severe reaction to certain drugs used during surgery and other invasive procedures. This reaction is called malignant hyperthermia. Malignant hyperthermia occurs in response to some anesthetic gases, which are used to block the sensation of pain, and with a particular type of muscle relaxant. If given these drugs, people at risk for malignant hyperthermia may experience muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), a high fever, increased acid levels in the blood and other tissues (acidosis), and a rapid heart rate. The complications of malignant hyperthermia can be life-threatening unless they are treated promptly.Central core disease gets its name from disorganized areas called cores, which are found in the center of muscle fibers in many affected individuals. These abnormal regions can only be seen under a microscope. Although the presence of cores can help doctors diagnose central core disease, it is unclear how they are related to muscle weakness and the other features of this condition.  https://ghr.nlm.nih.gov/condition/central-core-disease

Clinical features

Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot anomaly in which one or more of the arches of the foot have flattened out.
Dysplasia of acetabulum
MedGen UID:
9258
Concept ID:
C0019555
Congenital Abnormality
A spectrum of hip abnormalities commonly presenting in infancy involving the relationship between the femoral head and the acetabulum and that includes subluxation or dislocation at rest or upon provocation.
No development of motor milestones
MedGen UID:
892432
Concept ID:
C4020874
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Flexion contracture
MedGen UID:
3227
Concept ID:
C0009917
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Skeletal muscle atrophy
MedGen UID:
902598
Concept ID:
C0234958
Disease or Syndrome
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Generalized muscle weakness
MedGen UID:
155433
Concept ID:
C0746674
Sign or Symptom
A reduction in the strength of muscles in multiple anatomic sites.
Type 1 muscle fiber predominance
MedGen UID:
344274
Concept ID:
C1854387
Finding
An abnormal predominance of type I muscle fibers (in general, this feature can only be observed on muscle biopsy).
Neonatal hypotonia
MedGen UID:
412209
Concept ID:
C2267233
Disease or Syndrome
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.
Nemaline bodies
MedGen UID:
814369
Concept ID:
C3808039
Finding
Nemaline rods are abnormal bodies that can occur in skeletal muscle fibers. The rods can be observed on histological analysis of muscle biopsy tissue or upon electron microscopy, where they appear either as extensions of sarcomeric Z-lines, in random array without obvious attachment to Z-lines (often in areas devoid of sarcomeres) or in large clusters localized at the sarcolemma or intermyofibrillar spaces.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
A condition characterized by an abnormally high body temperature. In a hyperthermic state, the hypothalamic set-point is normal but body temperature increases and overrides the ability to lose heat, resulting from exogenous heat exposure or endogenous heat production.
Malignant hyperthermia susceptibility
MedGen UID:
9867
Concept ID:
C0024591
Disease or Syndrome
Malignant hyperthermia susceptibility (MHS) is a pharmacogenetic disorder of skeletal muscle calcium regulation associated with uncontrolled skeletal muscle hypermetabolism. Manifestations of malignant hyperthermia (MH) are precipitated by certain volatile anesthetics (i.e., halothane, isoflurane, sevoflurane, desflurane, enflurane), either alone or in conjunction with a depolarizing muscle relaxant (specifically, succinylcholine). The triggering substances release calcium stores from the sarcoplasmic reticulum and may promote entry of calcium from the myoplasm, causing contracture of skeletal muscles, glycogenolysis, and increased cellular metabolism, resulting in production of heat and excess lactate. Affected individuals experience: acidosis, hypercapnia, tachycardia, hyperthermia, muscle rigidity, compartment syndrome, rhabdomyolysis with subsequent increase in serum creatine kinase (CK) concentration, hyperkalemia with a risk for cardiac arrhythmia or even arrest, and myoglobinuria with a risk for renal failure. In nearly all cases, the first manifestations of MH (tachycardia and tachypnea) occur in the operating room; however, MH may also occur in the early postoperative period. There is mounting evidence that some affected individuals will also develop MH with exercise and/or on exposure to hot environments. Without proper and prompt treatment with dantrolene sodium, mortality is extremely high.
Flexion contracture
MedGen UID:
3227
Concept ID:
C0009917
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Dysplasia of acetabulum
MedGen UID:
9258
Concept ID:
C0019555
Congenital Abnormality
A spectrum of hip abnormalities commonly presenting in infancy involving the relationship between the femoral head and the acetabulum and that includes subluxation or dislocation at rest or upon provocation.
Kyphoscoliosis
MedGen UID:
154361
Concept ID:
C0575158
Anatomical Abnormality
An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.
Flexion contracture
MedGen UID:
3227
Concept ID:
C0009917
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCentral core disease

Professional guidelines

PubMed

Lillis S, Abbs S, Ferreiro A, Muntoni F, Jungbluth H
Eur J Hum Genet 2012 Feb;20(2) Epub 2011 Oct 19 doi: 10.1038/ejhg.2011.180. PMID: 22009146Free PMC Article
Lillis S, Abbs S, Mueller CR, Muntoni F, Jungbluth H
Eur J Hum Genet 2012 Feb;20(2) Epub 2011 Oct 12 doi: 10.1038/ejhg.2011.179. PMID: 21989361Free PMC Article

Recent clinical studies

Etiology

Zhao Y, Hu J, Zhao Z, Shen H, Bing Q, Li N
Muscle Nerve 2016 Sep;54(3):432-8. Epub 2016 May 25 doi: 10.1002/mus.25050. PMID: 26799446
Gu M, Zhang S, Hu J, Yuan Y, Wang Z, Da Y, Wu S
Neurosci Lett 2014 Apr 30;566:32-5. Epub 2014 Feb 20 doi: 10.1016/j.neulet.2014.02.015. PMID: 24561095
Kraeva N, Zvaritch E, Rossi AE, Goonasekera SA, Zaid H, Frodis W, Kraev A, Dirksen RT, Maclennan DH, Riazi S
Neuromuscul Disord 2013 Feb;23(2):120-32. Epub 2012 Nov 24 doi: 10.1016/j.nmd.2012.08.007. PMID: 23183335Free PMC Article
Chang X, Jin Y, Zhao H, Huang Q, Wang J, Yuan Y, Han Y, Qin J
J Child Neurol 2013 Mar;28(3):384-8. Epub 2012 May 1 doi: 10.1177/0883073812441251. PMID: 22550088
Sestero AM, Perra JH
Spine (Phila Pa 1976) 2005 Jan 15;30(2):E50-5. PMID: 15644748

Diagnosis

Zhao Y, Hu J, Zhao Z, Shen H, Bing Q, Li N
Muscle Nerve 2016 Sep;54(3):432-8. Epub 2016 May 25 doi: 10.1002/mus.25050. PMID: 26799446
Murayama T, Kurebayashi N, Yamazawa T, Oyamada H, Suzuki J, Kanemaru K, Oguchi K, Iino M, Sakurai T
PLoS One 2015;10(6):e0130606. Epub 2015 Jun 26 doi: 10.1371/journal.pone.0130606. PMID: 26115329Free PMC Article
Lee JS, Lim BC, Kim KJ, Hwang YS, Seong MW, Park SS, Park SH, Chae JH
Pediatr Int 2014 Dec;56(6):e88-91. doi: 10.1111/ped.12442. PMID: 25521991
Kraeva N, Zvaritch E, Rossi AE, Goonasekera SA, Zaid H, Frodis W, Kraev A, Dirksen RT, Maclennan DH, Riazi S
Neuromuscul Disord 2013 Feb;23(2):120-32. Epub 2012 Nov 24 doi: 10.1016/j.nmd.2012.08.007. PMID: 23183335Free PMC Article
Chang X, Jin Y, Zhao H, Huang Q, Wang J, Yuan Y, Han Y, Qin J
J Child Neurol 2013 Mar;28(3):384-8. Epub 2012 May 1 doi: 10.1177/0883073812441251. PMID: 22550088

Therapy

Schreuder LT, Nijhuis-van der Sanden MW, de Hair A, Peters G, Wortmann S, Bok LA, Morava E
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S205-9. Epub 2010 May 5 doi: 10.1007/s10545-010-9085-7. PMID: 20443062Free PMC Article
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Anaesthesia 2008 May;63(5):544-7. doi: 10.1111/j.1365-2044.2007.05411.x. PMID: 18412656
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Calore EE, Cavaliere MJ, Perez NM, Russo DH, Wakamatsu A, Razzouk D
Acta Neurol (Napoli) 1994 Aug;16(4):157-61. PMID: 7856468

Prognosis

Jungbluth H
Orphanet J Rare Dis 2007 May 15;2:25. doi: 10.1186/1750-1172-2-25. PMID: 17504518Free PMC Article
Zanette G, Robb N, Zadra N, Zanette L, Manani G
Paediatr Anaesth 2007 Apr;17(4):380-2. doi: 10.1111/j.1460-9592.2006.02108.x. PMID: 17359409
Polat M, Tosun A, Ay Y, Ozer E, Serdaroglu G, Aydogdu S, Gokben S, Tekgul H
J Child Neurol 2006 Feb;21(2):173-4. doi: 10.1177/08830738060210021301. PMID: 16566888
Gulati S, Salhotra A, Sharma MC, Sarkar C, Kalra V
Indian J Pediatr 2004 Nov;71(11):1021-4. PMID: 15572824
Manzur AY, Sewry CA, Ziprin J, Dubowitz V, Muntoni F
Neuromuscul Disord 1998 Oct;8(7):467-73. PMID: 9829276

Clinical prediction guides

Murayama T, Kurebayashi N, Yamazawa T, Oyamada H, Suzuki J, Kanemaru K, Oguchi K, Iino M, Sakurai T
PLoS One 2015;10(6):e0130606. Epub 2015 Jun 26 doi: 10.1371/journal.pone.0130606. PMID: 26115329Free PMC Article
Cuperman T, Fernandes SA, Lourenço NC, Yamamoto LU, Silva HC, Pavanello RC, Yamamoto GL, Zatz M, Oliveira AS, Vainzof M
BMC Res Notes 2014 Aug 1;7:487. doi: 10.1186/1756-0500-7-487. PMID: 25084811Free PMC Article
Schreuder LT, Nijhuis-van der Sanden MW, de Hair A, Peters G, Wortmann S, Bok LA, Morava E
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S205-9. Epub 2010 May 5 doi: 10.1007/s10545-010-9085-7. PMID: 20443062Free PMC Article
Davis MR, Haan E, Jungbluth H, Sewry C, North K, Muntoni F, Kuntzer T, Lamont P, Bankier A, Tomlinson P, Sánchez A, Walsh P, Nagarajan L, Oley C, Colley A, Gedeon A, Quinlivan R, Dixon J, James D, Müller CR, Laing NG
Neuromuscul Disord 2003 Feb;13(2):151-7. PMID: 12565913
Ferreiro A, Monnier N, Romero NB, Leroy JP, Bönnemann C, Haenggeli CA, Straub V, Voss WD, Nivoche Y, Jungbluth H, Lemainque A, Voit T, Lunardi J, Fardeau M, Guicheney P
Ann Neurol 2002 Jun;51(6):750-9. doi: 10.1002/ana.10231. PMID: 12112081

Recent systematic reviews

Orlov D, Keith J, Rosen D, Croul S, Kraeva N, Riazi S
Can J Anaesth 2013 Oct;60(10):982-9. Epub 2013 Jul 26 doi: 10.1007/s12630-013-0005-9. PMID: 23888335
Lehmann-Horn F, Jurkat-Rott K, Rüdel R; Ulm Muscle Centre.
Acta Myol 2008 Dec;27:98-113. PMID: 19472919Free PMC Article

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