We studied seven patients (fetuses/infants) from six unrelated families affected by central core disease (CCD) and presenting with a fetal akinesia syndrome. [ncbi.nlm.nih.gov]

A recessive form of central core disease, transiently presenting as multi-minicore disease, is associated with a homozygous mutation in the ryanodine receptor type 1 gene. [archive-ouverte.unige.ch]

Recessive central core disease is less common and often more severe, and it presents at a younger age. [medlink.com]

• Hyperthermia

  Genetic Defects mutation of the ryanodine receptor -> two clinical phenotypes: Central Core Disease Malignant Hyperthermia that Central Core Disease and Malignant Hyperthermia are both associated with mutations in the RYR1 gene was first demonstra-ted [pedbase.org]

  North American Malignant Hyperthermia Group. Anesth Analg. 1989 Oct; 69 (4):511–515. [ PubMed ] [ Google Scholar ] Jurkat-Rott K, McCarthy T, Lehmann-Horn F. Genetics and pathogenesis of malignant hyperthermia. [ncbi.nlm.nih.gov]

• Fever

  Some individuals with CCD have an increased chance of having a severe reaction to anesthesia, called malignant hyperthermia, which may cause muscle rigidity or break-down (rhabdomyolysis), a high fever, or a rapid heart beat. [diseaseinfosearch.org]

  Some individuals with CCD have an increased chance of having a severe reaction to anesthesia, called malignant hyperthermia, which may cause muscle rigidity or breakdown (rhabdomyolysis), a high fever, or a rapid heartbeat. [genpharmservices.com]

  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. [mhaus.org]

  Some individuals with CCD have an increased chance of having a severe reaction to anesthesia, called malignant hyperthermia, which may cause muscle rigidity or break-down ( rhabdomyolysis ), a high fever, or a rapid heart beat. [1] [2] RYR1 is the only [rarediseases.info.nih.gov]

  Symptoms of MH include high fever, muscle rigidity, dark brown colouration of urine and acute kidney failure. MH is potentially fatal if not treated immediately with a drug called dantrolene. [musculardystrophyuk.org]

• Congestive Heart Failure

  Heart Failure 422 Case 67 An Elderly Woman with a Progressive Neuropathy 429 Case 68 A Young Woman with Difficulty Swallowing 433 Case 69 A Young Woman with Intermittent Weakness and a Positive Family History of Similar Problems 436 Case 70 A Woman with [books.google.com]

  However, heart failure from DCM is a common cause of death in the mid-40s. DMD-associated DCM is characterized by left ventricular dilation and congestive heart failure. [blueprintgenetics.com]

  Comparison of hemodynamic responses to cycling and resistance exercise in congestive heart failure secondary to ischemic cardiomyopathy. [ahajournals.org]

• Difficulty Walking

  Walking and Ataxia 415 Case 66 A Man with Progressive Neuropathy and Congestive Heart Failure 422 Case 67 An Elderly Woman with a Progressive Neuropathy 429 Case 68 A Young Woman with Difficulty Swallowing 433 Case 69 A Young Woman with Intermittent [books.google.com]

• Weight Loss

  Loss and Lung Nodules 411 Case 65 A Woman with Difficulty Walking and Ataxia 415 Case 66 A Man with Progressive Neuropathy and Congestive Heart Failure 422 Case 67 An Elderly Woman with a Progressive Neuropathy 429 Case 68 A Young Woman with Difficulty [books.google.com]

• Skin Rash

  Rash 559 Case 90 A Man with Muscle Pains 567 Case 91 An Older Woman with Progressive Muscle Weakness 572 Case 92 An HIVInfected Man with Muscle Weakness and Spasms 577 Case 93 A Woman with Limb Swelling and Pain 581 Case 94 A Man with a Bent Spine 584 [books.google.com]

  Other symptoms of myopathy may include: muscle cramps or spasms stiffness muscle pain low energy and fatigue exercise intolerance skin rashes Some myopathy symptoms are present at birth, and others develop later in life. [medicalnewstoday.com]

• Diplopia

  An Older Woman with Progressive Muscle Weakness 572 Case 92 An HIVInfected Man with Muscle Weakness and Spasms 577 Case 93 A Woman with Limb Swelling and Pain 581 Case 94 A Man with a Bent Spine 584 Case 95 A Man with Muscle Stiffness and Later with Diplopia [books.google.com]

• Myopathy

  […] congenital myopathies (CM), central core disease (CCD), and multiminicore disease (MmD). [medlink.com]

  This review will focus on myotubular myopathy, centronuclear myopathy, central core disease, and congenital neuromuscular disease with uniform Type 1 fiber, myopathies that are subjects of our ongoing examinations. [ncbi.nlm.nih.gov]

  […] dystrophy Muscular dystrophy, congenital hereditary Muscular dystrophy, hereditary, congenital Myopathy, central core Myopathy, congenital Myopathy, myotubular Myotubular myopathy Walker Walbug muscular dystrophy, congenital Walker walburg congenital [icd9data.com]

• Foot Deformity

  Deformities 510 Case 81 A Woman with Droopy Eyelids and Ophthalmoplegia 515 Case 82 A Man with Weakness and Swelling in the Neck 522 Case 83 A Woman with Muscle Pains and Dark Urine 526 Case 84 A Woman with Progressive Proximal Muscle Weakness 533 Case [books.google.com]

  deformities ( Neurology 2013;80:1584 ), but most patients can walk independently Extraocular, respiratory, cardiac muscle involvement is uncommon Precautions with general anesthesia due to risk of malignant hyperthermia (associated with RYR1 mutation [pathologyoutlines.com]

  The central core disease is also associated with joint deformities, hip dislocation, foot deformities, the rounded upper portion of the back that curves to one side (kyphoscoliosis), and also, eyes that do not look in the same direction (strabismus). [icliniq.com]

  Central core disease is also associated with eyes that do not look in the same direction (strabismus), a rounded upper back that also curves to the side (kyphoscoliosis), foot deformities, hip dislocation, and joint deformities called contractures that [medlineplus.gov]

  Other possible features include congenital hip dislocation, scoliosis, and foot deformities. Cardiomyopathy and ophthalmoplegia are not typical features of CCD. [invitae.com]

• Myalgia

  Read Full » Most Popular Articles Do you have a question on Myalgia or Central Core Disease? Ask a Doctor Online * guaranteed answer within 4 hours. [icliniq.com]

  Autosomal dominant forms typically manifest in adolescence or adulthood with exercise-induced myalgia, bifacial weakness, ptosis, and external ophthalmoplegia. [merckmanuals.com]

  […] mutations ( Semin Pediatr Neurol 2011;18:239 ) Clinical features Variable presentation Static to slowly progressive disease course May worsen or progress during or after pregnancy Usually presents in infancy or early childhood Most common symptoms: myalgias [pathologyoutlines.com]

  Symptoms can range from mild cramps to more-severe myalgias, pain, and weakness. Rhabdomyolosis has also been reported in rare cases. [clevelandclinicmeded.com]

• Leg Weakness

  Case 58A A Woman with Leg Numbness Pain Weakness and Slow Nerve Conduction Velocities 372 Case 58B A Boy with Leg Weakness 375 Case 59 A Man with Hand Weakness and Numbness After Skiing 383 Case 60 A Man with Recurrent Foot Drop 386 Case 61 An Elderly [books.google.com]

  The childhood-onset form presents with distal leg weakness in the late first or early second decade. Proximal muscles are involved later, and wheelchair dependency occurs in midlife. [emedicine.medscape.com]

• Dark Urine

  […] and Later Contractures 503 Case 80 A Woman with Longstanding Weakness and Foot Deformities 510 Case 81 A Woman with Droopy Eyelids and Ophthalmoplegia 515 Case 82 A Man with Weakness and Swelling in the Neck 522 Case 83 A Woman with Muscle Pains and Dark [books.google.com]

  Muscle disease could also present with dark urine as a sign of renal damage in the case of rhabdomyolysis, particularly after vigorous exercises like running marathons[4]. [physio-pedia.com]

  In metabolic myopathies associated with rhabdomyolysis (defined as creatine kinase elevation 10 times the normal value), patients may report tea-colored or dark urine, especially after intense exercise. [clevelandclinicmeded.com]

• Excitement

  Ca 2+ -dependent Ca 2+ release 45 Ca 2+ uptake and release excitation–contraction coupling central core disease ryanodine receptor skeletal-muscle sarcoplasmic reticulum Abbreviations: CCD, central core disease; DHPR, dihydropyridine receptor; EC, excitation–contraction [biochemj.org]

  We found that excitation-coupled calcium entry is strongly enhanced in cells from patients with CCD compared with individuals with MH and controls. [ncbi.nlm.nih.gov]

  The main pathogenetic mechanisms implicated in typical CCD are altered excitability ("Excitation-contraction uncoupling hypothesis") and changes in calcium homeostasis ("Leaky channel hypothesis") within muscle cells but may be distinct in other RYR1- [myobase.org]

• Neonatal Hypotonia

  Severe cases present as neonatal hypotonia and contractures Skeletal : Increased incidence of congenital dislocation of hips and scoliosis Malignant hyperthermia : increased susceptibility. [genetics4medics.com]

  Neonatal hypotonia MedGen UID: 412209 •Concept ID: C2267233 • Disease or Syndrome Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period. [ncbi.nlm.nih.gov]

  hypotonia Low muscle tone, in neonatal onset 0001319 Nonprogressive 0003680 Skeletal muscle atrophy Muscle degeneration Muscle wasting [ more ] 0003202 Slow progression Signs and symptoms worsen slowly with time 0003677 Showing of 33 | Last updated: [rarediseases.info.nih.gov]

  Monnier N, Laquerriere A, Marret S et al : First genomic rearrangement of the RYR1 gene associated with an atypical presentation of lethal neonatal hypotonia. Neuromuscul Disord 2009; 19 : 680–684. 22. [nature.com]

• Areflexia

  Recessive mutations of satellite cell gene ( MEGF10 ) are defined in patients with early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARRD). [medlink.com]

  67 An Elderly Woman with a Progressive Neuropathy 429 Case 68 A Young Woman with Difficulty Swallowing 433 Case 69 A Young Woman with Intermittent Weakness and a Positive Family History of Similar Problems 436 Case 70 A Woman with Muscle Weakness and Areflexia [books.google.com]

  Clinical phenotype is characterized by early-onset myopathy, areflexia, respiratory distress, and dysphagia (EAMRDD). [ncbi.nlm.nih.gov]

  Dilated cardiomyopathy (DCM), Mandibuloacral dysplasia type A, Progeria Hutchinson-Gilford type AD/AR 250 564 LMOD3 Severe congenital nemaline myopathy, Typical nemaline myopathy AR 8 15 MAP3K20 Centronuclear myopathy AR 5 7 MEGF10 Myopathy, early-onset, areflexia [blueprintgenetics.com]

• Ataxia

  […] and retinitis pigmentosa; SANDO, sensory ataxic neuropathy, dysarthria and ophthalmoparesis; MSCAE, mitochondrial spinocerebellar ataxia and epilepsy; MIRAS, mitochondrial recessive ataxia syndrome; ad/ar PEO, autosomal dominant or recessive progressive [musculoskeletalkey.com]

  Arthritis Who Developed Numbness and Pain in the Feet 399 Case 63 A Woman with Granulomatous Lesions in the Lungs and a Peripheral Neuropathy 405 Case 64 A Man with a Neuropathy Weight Loss and Lung Nodules 411 Case 65 A Woman with Difficulty Walking and Ataxia [books.google.com]

  43, Charcot-Marie-Tooth disease, axonal, type 2T AD/AR 14 21 MSTO1#* Myopathy, mitochondrial, and ataxia AR 7 8 MT-ATP6 Neuropathy, ataxia, and retinitis pigmentosa, Leber hereditary optic neuropathy, Ataxia and polyneuropathy, adult-onset, Cardiomyopathy [blueprintgenetics.com]

  AD 100 88 of 88 TSEN2 Pontocerebellar Hypoplasia AR 95.47 4 of 5 TSEN54 Fatal Infantile Encephalopathy With Olivopontocerebellar Hypoplasia AR 96.94 20 of 22 UBA1 Infantile-Onset X- linked Spinal Muscular Atrophy X,XR,G 99.58 NA of NA VAMP1 Spastic Ataxia [igenomix.es]

• Foot Drop

  Case 58A A Woman with Leg Numbness Pain Weakness and Slow Nerve Conduction Velocities 372 Case 58B A Boy with Leg Weakness 375 Case 59 A Man with Hand Weakness and Numbness After Skiing 383 Case 60 A Man with Recurrent Foot Drop 386 Case 61 An Elderly [books.google.com]

  drop; affected muscles almost always lack reflexes Myotonia congenita: voluntary muscles of the arms, legs, and face are stiff or slow to relax after contracting (myotonia); stiffness triggered by fatigue, stress, cold, or long rest periods, such as [medical-dictionary.thefreedictionary.com]

  Centronuclear myopathy: weakness of voluntary muscles, including those on the face, arms, legs, and trunk; drooping upper eyelids; facial weakness; foot drop; affected muscles almost always lack reflexes. [healthofchildren.com]

• Slow Nerve Conduction Velocity

  Case 58A A Woman with Leg Numbness Pain Weakness and Slow Nerve Conduction Velocities 372 Case 58B A Boy with Leg Weakness 375 Case 59 A Man with Hand Weakness and Numbness After Skiing 383 Case 60 A Man with Recurrent Foot Drop 386 Case 61 An Elderly [books.google.com]

• Creatine Phosphokinase Increased

  […] kinase Elevated blood creatine phosphokinase Elevated circulating creatine phosphokinase Elevated creatine kinase Elevated serum CPK Elevated serum creatine phosphokinase High serum creatine kinase Increased CPK Increased creatine kinase Increased creatine [rarediseases.info.nih.gov]

• Hypercholesterolemia

  Strength training and hypercholesterolemia: an epidemiologic study of 8499 employed men. Am J Health Promot. 1996; 11: 35–41.CrossrefMedlineGoogle Scholar 83 Kohl HW 3rd, Gordon NF, Scott CB, Vaandrager H, Blair SN. [ahajournals.org]

We report on a 9-year-old boy with central core disease and mitochondrial dysfunction due to compound heterozygous RYR1 mutations receiving albuterol treatment for 1 year. [ncbi.nlm.nih.gov]

Is there a treatment or cure? Currently there is no treatment or cure for central core disease, but there are some important ways to manage the condition. Physiotherapy. [musculardystrophyuk.org]

Curative treatment is not available for this condition and is managed by supportive and symptomatic treatment through physiotherapy and genetic counseling. [icliniq.com]

Management and treatment Management is mainly supportive and has to anticipate susceptibility to potentially life-threatening reactions to general anaesthesia. [orpha.net]

Prognosis In the majority of patients, weakness is static or only slowly progressive, with a favourable long-term outcome. [orpha.net]

The 3 most common types of congenital myopathy, in order, are Central core and multiminicore myopathies (core myopathies) Centronuclear myopathy Nemaline myopathy The types are distinguished primarily by their histologic features, symptoms, and prognosis [merckmanuals.com]

[…] magnus of thigh, as well as soleus and peroneal group of lower leg Relative sparing of gracilis, adductor longus and rectus femoris ( Neurology 2013;80:1584 ) Prognostic factors Autosomal dominant mutations are typically associated with a favorable prognosis [pathologyoutlines.com]

What is the prognosis? In most cases, symptoms become apparent at birth or shortly after. They include hypotonia (floppiness) and weakness of the muscles closest to the trunk of the body. [musculardystrophyuk.org]

[…] channel properties of RyR1s carrying one recurrent and two novel mutations upholds the view that diminished intracellular Ca(2+) release caused by impaired Ca(2+) channel gating and/or Ca(2+) permeability is an important component of central core disease etiology [ncbi.nlm.nih.gov]

Etiology CCD and MHS are allelic conditions, both caused by (predominantly dominant) mutations in the skeletal muscle ryanodine receptor (RYR1) gene, encoding the principal skeletal muscle sarcoplasmic reticulum calcium release channel (RyR1). [orpha.net]

Rhabdomyolysis may also be seen with infectious etiologies, alcohol, and toxic exposures. [clevelandclinicmeded.com]

[…] of skeletal muscle fibers, as seen on enzymatic stains such as NADH Epidemiology One of the more common congenital myopathies but true incidence is unknown Sites Predominantly involves proximal musculature Most frequently hip girdle and axial muscles Etiology [pathologyoutlines.com]

However, the lack of response to immunotherapy raised suspicion of another etiology, and muscle biopsy findings suggested MmD. Our patient and her brother partially met the clinical diagnostic criteria of MmD. [e-acn.org]

EPIDEMIOLOGY: incidence: ? age of onset: newborn -> infancy risk factors: familial - autosomal dominant chrom.#: 19q13.1 gene: ryanodine receptor (RYR1) M = F PATHOGENESIS: 1. [pedbase.org]

[…] genetic investigations aimed at solving heterogeneity and discordance issues in MHS; new initiatives aimed at identifying modulating factors that influence the penetrance of clinical MH in MHS individuals; and detailed studies aimed at describing the full epidemiological [ncbi.nlm.nih.gov]

Summary Epidemiology Prevalence is unknown. Clinical description CCD typically presents in infancy with hypotonia and motor developmental delay and is characterized by predominantly proximal weakness, pronounced in the hip girdle. [orpha.net]

[…] weakness is insufficient for diagnosis of central core disease Terminology "Central core" refers to areas of reduced oxidative and glycolytic enzymatic activity along the longitudinal axis of skeletal muscle fibers, as seen on enzymatic stains such as NADH Epidemiology [pathologyoutlines.com]

Epidemiology[edit | edit source] Most common type of myopathy: Inflammatory and endocrine myopathies (usually in middle-aged women> men). Prevalence varies between 2.4 to 33.8 per 100,000 population. [physio-pedia.com]

The review is also focused on discussing novel results in regard to pathophysiological consequences of specific MH/CCD RyR1 mutant proteins, which are representative of the different cellular mechanisms that are linked to either phenotype. [ncbi.nlm.nih.gov]

[citation needed] Pathophysiology[edit] Central core disease has an autosomal dominant pattern of inheritance. Central core disease is inherited in an autosomal dominant fashion. [en.wikipedia.org]

Recessive inheritance in CCD may therefore be more common than previously appreciated, which has important implications for genetic counseling and MH prevention in affected families. [ncbi.nlm.nih.gov]

Physiotherapy may be helpful in most cases by preventing the development of contractures, maintaining breathing capacity, and delaying the development of spine curvature. [icliniq.com]

MH can be prevented by avoiding the triggering anaesthetic agents with alternative drugs. Local anaesthetics are quite safe. [musculardystrophyuk.org]