Central core disease

Last updated
Central Core Disease
Other namesCentral core myopathy
Cell sample of muscle tissue with central core disease (stained for contrast).jpg
Histopathologic appearance of typical central core disease: NADH-TR, transverse section from the rectus femoris. Marked predominance of dark staining, high oxidative type 1 fibres with cores affecting the majority of fibres. Cores are typically well demarcated and centrally located (→), but may occasionally be multiple and of eccentric location.
Specialty Neurology   OOjs UI icon edit-ltr-progressive.svg

Central core disease (CCD), also known as central core myopathy, is an autosomal dominantly inherited [1] muscle disorder present from birth that negatively affects the skeletal muscles. It was first described by Shy and Magee in 1956. [2] [3] It is characterized by the appearance of the myofibril under the microscope. [4]

Contents

Signs and symptoms

The symptoms of CCD are variable, but usually involve hypotonia (decreased muscle tone) at birth, mild delay in child development (highly variable between cases), weakness of the facial muscles, and skeletal malformations such as scoliosis and hip dislocation. [2]

CCD is usually diagnosed in infancy or childhood, but some patients remain asymptomatic until adulthood to middle age. [5] While generally not progressive, there appears to be a growing number of people who do experience a slow clinically significant progression of symptomatology. These cases may be due to the large number of mutations of ryanodine receptor malfunction, and with continued research may be found to be clinical variants.[ citation needed ]

Pathophysiology

Central core disease has an autosomal dominant pattern of inheritance. Autosomal dominant - en.svg
Central core disease has an autosomal dominant pattern of inheritance.

Central core disease is inherited in an autosomal dominant fashion. Most cases have demonstrable mutations in the ryanodine receptor type 1 (RYR1) gene, [1] which are often de novo (newly developed). People with CCD are at increased risk for developing malignant hyperthermia (MH) when receiving general anesthesia. [2]

Diagnosis

The diagnosis is made based on the combination of typical symptoms and the appearance on biopsy (tissue sample) from muscle. The name derives from the typical appearance of the biopsy on light microscopy, where the muscle cells have cores that are devoid of mitochondria and specific enzymes. [2]

Respiratory insufficiency develops in a small proportion of cases. Creatine kinase tend to be normal and electromyography (EMG) shows short duration, short amplitude motor unit action potentials. [2]

Treatment

There is no specific treatment but triggering anesthetics are avoided and relatives are screened for RYR1 mutations as these may make them susceptible to MH. [2]

Related Research Articles

Suxamethonium chloride

Suxamethonium chloride, also known as suxamethonium or succinylcholine, is a medication used to cause short-term paralysis as part of general anesthesia. This is done to help with tracheal intubation or electroconvulsive therapy. It is given either by injection into a vein or muscle. When used in a vein onset of action is generally within one minute and effects last for up to 10 minutes.

Dantrolene

Dantrolene sodium, sold under the brand name Dantrium among others, is a postsynaptic muscle relaxant that lessens excitation-contraction coupling in muscle cells. It achieves this by inhibiting Ca2+ ions release from sarcoplasmic reticulum stores by antagonizing ryanodine receptors. It is the primary drug used for the treatment and prevention of malignant hyperthermia, a rare, life-threatening disorder triggered by general anesthesia. It is also used in the management of neuroleptic malignant syndrome, muscle spasticity (e.g. after strokes, in paraplegia, cerebral palsy, or patients with multiple sclerosis), and poisoning by 2,4-dinitrophenol or by the related compounds dinoseb and dinoterb.

Malignant hyperthermia Medical condition

Malignant hyperthermia (MH) is a type of severe reaction that occurs in response to particular medications used during general anesthesia, among those who are susceptible. Symptoms include muscle rigidity, high fever, and a fast heart rate. Complications can include muscle breakdown and high blood potassium. Most people who are susceptible are generally otherwise unaffected when not exposed.

Ryanodine receptors form a class of intracellular calcium channels in various forms of excitable animal tissue like muscles and neurons. There are three major isoforms of the ryanodine receptor, which are found in different tissues and participate in different signaling pathways involving calcium release from intracellular organelles. The RYR2 ryanodine receptor isoform is the major cellular mediator of calcium-induced calcium release (CICR) in animal cells.

Nemaline myopathy is a congenital, often hereditary neuromuscular disorder with many symptoms that can occur such as muscle weakness, hypoventilation, swallowing dysfunction, and impaired speech ability. The severity of these symptoms varies and can change throughout one's life to some extent. The prevalence is estimated at 1 in 50,000 live births. It is the most common non-dystrophic myopathy.

Centronuclear myopathy Medical condition

Centronuclear myopathies (CNM) are a group of congenital myopathies where cell nuclei are abnormally located in the center of muscle cells instead of their normal location at the periphery.

Equine polysaccharide storage myopathy is a hereditary glycogen storage disease of horses that causes exertional rhabdomyolysis. It is currently known to affect the following breeds American Quarter Horses, American Paint Horses, Warmbloods, Cobs, Dales Ponies, Thoroughbreds, Arabians, New Forest ponies, and a large number of Heavy horse breeds. While incurable, PSSM can be managed with appropriate diet and exercise. There are currently 2 subtypes, known as Type 1 PSSM and Type 2 PSSM.

Catecholaminergic polymorphic ventricular tachycardia Medical condition

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited genetic disorder that predisposes those affected to potentially life-threatening abnormal heart rhythms or arrhythmias. The arrhythmias seen in CPVT typically occur during exercise or at times of emotional stress, and classically take the form of bidirectional ventricular tachycardia or ventricular fibrillation. Those affected may be asymptomatic, but they may also experience blackouts or even sudden cardiac death.

Congenital myopathy is a very broad term for any muscle disorder present at birth. This defect primarily affects skeletal muscle fibres and causes muscular weakness and/or hypotonia. Congenital myopathies account for one of the top neuromuscular disorders in the world today, comprising approximately 6 in 100,000 live births every year. As a whole, congenital myopathies can be broadly classified as follows:

Chronic progressive external ophthalmoplegia (CPEO), is a type of eye disorder characterized by slowly progressive inability to move the eyes and eyebrows. It is often the only feature of mitochondrial disease, in which case the term CPEO may be given as the diagnosis. In other people suffering from mitochondrial disease, CPEO occurs as part of a syndrome involving more than one part of the body, such as Kearns–Sayre syndrome. Occasionally CPEO may be caused by conditions other than mitochondrial diseases.

Ryanodine receptor 2

Ryanodine receptor 2 (RYR2) is a protein found primarily in cardiac muscle. In humans, it is encoded by the RYR2 gene. In the process of cardiac calcium-induced calcium release, RYR2 is the major mediator for sarcoplasmic release of stored calcium ions.

Ca<sub>v</sub>1.1

Cav1.1 also known as the calcium channel, voltage-dependent, L type, alpha 1S subunit, (CACNA1S), is a protein which in humans is encoded by the CACNA1S gene. It is also known as CACNL1A3 and the dihydropyridine receptor.

Ryanodine receptor 1

Ryanodine receptor 1 (RYR-1) also known as skeletal muscle calcium release channel or skeletal muscle-type ryanodine receptor is a protein found primarily in skeletal muscle. In humans, it is encoded by the RYR1 gene.

RYR3

Ryanodine receptor 3 is a protein that in humans is encoded by the RYR3 gene. The protein encoded by this gene is both a calcium channel and a receptor for the plant alkaloid ryanodine. RYR3 and RYR1 control the resting calcium ion concentration in skeletal muscle.

Marinesco–Sjögren syndrome (MSS), sometimes spelled Marinescu–Sjögren syndrome, is a rare autosomal recessive disorder.

X-linked myotubular myopathy Medical condition

X-linked myotubular myopathy (MTM) is a form of centronuclear myopathy (CNM) associated with myotubularin 1.

Multi/minicore myopathy is a congenital myopathy usually caused by mutations in either the SEPN1 and RYR1 genes. It is chartacterised the presence of multifocal, well-circumscribed areas with reduction of oxidative staining and low myofibrillar ATPase on muscle biopsy. It is also known as Minicore myopathy, Multicore myopathy, Multiminicore myopathy, Minicore myopathy with external ophthalmoplegia, Multicore myopathy with external ophthalmoplegia and Multiminicore disease with external ophthalmoplegia.

Brody myopathy Medical condition

Brody myopathy is a rare disorder that affects skeletal muscle function. BD was first characterized in 1969 by Dr. Irwin A. Brody at Duke University Medical Center. Individuals with BD have difficulty relaxing their muscles after exercise. This difficulty in relaxation leads to symptoms including cramps, stiffness, and discomfort in the muscles of the limbs and face. Symptoms are heightened by exercise and commonly progress in severity throughout adulthood.

Desmin-related myofibrillar myopathy, also called Helmer’s myopathy, is a subgroup of the myofibrillar myopathy diseases and is the result of a mutation in the gene that codes for desmin which prevents it from forming protein filaments, instead forming aggregates of desmin and other proteins throughout the cell.

Kathryn Stowell New Zealand biomedical researcher

Kathryn Mary Stowell is a New Zealand academic. She is currently a full professor at the Massey University.

References

  1. 1 2 Robinson, Rl; Brooks, C; Brown, Sl; Ellis, Fr; Halsall, Pj; Quinnell, Rj; Shaw, Ma; Hopkins, Pm (August 2002). "RYR1 mutations causing central core disease are associated with more severe malignant hyperthermia in vitro contracture test phenotypes". Human Mutation. 20 (2): 88–97. doi:10.1002/humu.10098. PMID   12124989. S2CID   21497303.
  2. 1 2 3 4 5 6 Quinlivan RM, Muller CR, Davis M, et al. (2003). "Central core disease: clinical, pathological, and genetic features". Arch. Dis. Child. 88 (12): 1051–5. doi:10.1136/adc.88.12.1051. PMC   1719384 . PMID   14670767.
  3. Magee KR, Shy GM (1956). "A new congenital non-progressive myopathy". Brain. 79 (4): 610–21. CiteSeerX   10.1.1.1026.496 . doi:10.1093/brain/79.4.610. PMID   13396066.
  4. " central core disease " at Dorland's Medical Dictionary
  5. Talwalkar, SS; Parker, JR; Heffner, RR; Parker, JC (2006). "Adult central core disease. Clinical, histologic and genetic aspects: case report and review of the literature". Clin Neuropathol. 25 (4): 180–4. PMID   16866299.
Classification
D
External resources