Duchenne Muscular Dystrophy

Overview

Epidemiology

Duchenne muscular dystrophy Muscular Dystrophy Becker Muscular Dystrophy (DMD) is the most common and most severe muscular dystrophy Muscular Dystrophy Becker Muscular Dystrophy.

• Affects boys
• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 1 in 3,500 boys worldwide
• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 63 cases per million

Etiology

Duchenne muscular dystrophy Muscular Dystrophy Becker Muscular Dystrophy results from a mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in the dystrophin Dystrophin A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. Blotting Techniques (DMD) gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics on the short arm Arm The arm, or “upper arm” in common usage, is the region of the upper limb that extends from the shoulder to the elbow joint and connects inferiorly to the forearm through the cubital fossa. It is divided into 2 fascial compartments (anterior and posterior). Arm: Anatomy of the X chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics.

• DMD is the largest known protein-coding human gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics associated with an increased risk for mutations.
• Most commonly inherited X-linked X-linked Genetic diseases that are linked to gene mutations on the X chromosome in humans or the X chromosome in other species. Included here are animal models of human X-linked diseases. Common Variable Immunodeficiency (CVID) recessive pattern
• ⅓ of mutations occur from a de novo frameshift mutation Frameshift Mutation A type of mutation in which a number of nucleotides deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the reading frames of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. Types of Mutations.

Pathophysiology

Normal physiology:

• DMD gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics encodes for normal dystrophin Dystrophin A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. Blotting Techniques protein, which is essential for the structural stability of myofibers.
• Dystrophin Dystrophin A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. Blotting Techniques forms a large glycoprotein complex (dystrophin-associated glycoprotein complex):
  • Acts as a mechanical link between the cytoskeleton Cytoskeleton The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. The Cell: Cytosol and Cytoskeleton and extracellular matrix Extracellular matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Hypertrophic and Keloid Scars of muscle 
  • Allows for normal muscle function

Pathophysiology of DMD:

• Mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in the DMD gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics that encodes dystrophin Dystrophin A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. Blotting Techniques, leading to abnormal dystrophin Dystrophin A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. Blotting Techniques protein
• Abnormal dystrophin Dystrophin A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. Blotting Techniques is unable to form a functional glycoprotein complex → defective mechanical link between the cytoskeleton Cytoskeleton The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. The Cell: Cytosol and Cytoskeleton and extracellular matrix Extracellular matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Hypertrophic and Keloid Scars of muscle
• Abnormal glycoprotein complex is degraded by proteases Proteases Proteins and Peptides → loss of dystrophin Dystrophin A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. Blotting Techniques 
• Muscles are more susceptible to damage → inadequate attempts at muscle regeneration Regeneration The physiological renewal, repair, or replacement of tissue. Wound Healing → replacement of muscle with fibrous Fibrous Fibrocystic Change and fatty tissue

Clinical Presentation

Presentation

Duchenne muscular dystrophy Muscular Dystrophy Becker Muscular Dystrophy presents with progressive muscle weakness.

• Initially, the proximal muscles are affected.
• DMD 1st affects the lower extremities, and then progresses to the neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, shoulders, and arms.

Timeline:

• Myopathy Myopathy Dermatomyositis is present at birth.
• Clinical symptoms present at 2–3 years of age.
• Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are non-ambulatory by 12 years of age.
• Death due to cardiac or respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure at about 20 years of age

Clinical course:

• Early ambulatory stage:
  • Delay in attaining motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology skills (e.g., head lag Head Lag Developmental Milestones and Normal Growth, late walker)
  • Difficulty in running and jumping
  • Toe walking Toe Walking Becker Muscular Dystrophy
  • Clumsiness
• Late ambulatory stage: 
  • Increased difficulty in walking
  • Cannot arise from the floor
  • Difficulty climbing stairs
  • Easily fatigued
• Early nonambulatory stage:
  • Unable to ambulate, but can self-propel for short periods
  • Can maintain posture
  • Scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis starts to develop.
• Late nonambulatory stage:
  • Unable to maintain posture
  • Contractures Contractures Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint. Wound Healing start to develop.

Exam findings

• Waddling gait Gait Manner or style of walking. Neurological Examination
• Gower’s sign: 
  • The use of arms and hands to maneuver the body to a standing position
  • Results from proximal muscle weakness Proximal Muscle Weakness Lambert-Eaton Myasthenic Syndrome
  • Pathognomonic
• Calf pseudohypertrophy: 
  • Large but weak gastrocnemius Gastrocnemius Leg: Anatomy muscle 
  • Due to replacement of muscle with fibrous Fibrous Fibrocystic Change and fatty tissue
• Hypotonia and muscle wasting
• Scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis and lumbar lordosis
• Hyporeflexia or areflexia
• Contractures Contractures Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint. Wound Healing occur often:
  • Knees
  • Hips
  • Ankles
  • Elbows

Diagnosis

Muscle enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes

• ↑ CK: 
  • Found before clinical signs appear
  • Often > 10–20 times the upper normal limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation
  • Levels peak at 2 years of age and gradually decline as muscle is replaced by fibrous Fibrous Fibrocystic Change and fatty tissue.
• ↑ Aldose Aldose Basics of Carbohydrates
• ↑ AST AST Enzymes of the transferase class that catalyze the conversion of l-aspartate and 2-ketoglutarate to oxaloacetate and l-glutamate. Liver Function Tests and ALT ALT An enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate. Liver Function Tests

Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies

• Multiplex ligation-dependent probe Probe A device placed on the patient’s body to visualize a target Ultrasound (Sonography) amplification (MLPA): 
  • To identify abnormalities in the DMD gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics
  • Primary confirmatory test
• Complete gene sequencing Gene sequencing Polymerase Chain Reaction (PCR): 
  • Can detect small genetic changes
  • Used if MLPA is negative, but clinical suspicion is high
• Other techniques:
  • PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR)
  • FISH FISH A type of in situ hybridization in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei. Chromosome Testing

Muscle biopsy Muscle Biopsy Trichinella/Trichinellosis

• Indicated if genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies is not confirmatory, but clinical suspicion remains high
• Findings:
  • Necrotic muscle fibers of varying sizes
  • Replacement of muscle with fat and fibrous Fibrous Fibrocystic Change tissue
  • Immunostaining reveals the absence of dystrophin Dystrophin A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. Blotting Techniques.

Electromyography Electromyography Recording of the changes in electric potential of muscle by means of surface or needle electrodes. Becker Muscular Dystrophy (EMG)

• Almost never used, but may help differentiate DMD from other forms of muscle weakness
• Shows small polyphasic potentials

Management

There is no cure for DMD. Management is mainly supportive and palliative, and often guided by individual preferences.

Medical management

• Multidisciplinary care Multidisciplinary Care Becker Muscular Dystrophy is required.
• Physical therapy Physical Therapy Becker Muscular Dystrophy and exercise to regain muscle strength Muscle strength The amount of force generated by muscle contraction. Muscle strength can be measured during isometric, isotonic, or isokinetic contraction, either manually or using a device such as a muscle strength dynamometer. Neurological Examination and prevent contractures Contractures Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint. Wound Healing
• Fall prevention and use of mobility Mobility Examination of the Breast aids AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS
• Nutritional support
• Appropriate mental-health screening Screening Preoperative Care and support

Medical therapy

• Corticosteroids Corticosteroids Chorioretinitis (e.g., prednisone Prednisone A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. Immunosuppressants, deflazacort): 
  • Slows the progression of muscle weakness 
  • Delays the loss of ambulation
  • Reduces the risk of scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis
  • Improves pulmonary function
  • Chronic use is often limited by side effects.
  • Avoid abrupt cessation to prevent adrenal crisis Adrenal crisis Adrenal crisis is the acute decompensation of adrenal function that can be triggered by another disease, surgery, stress, or increased glucocorticoid inactivation. Adrenal Insufficiency and Addison’s Disease.
• Creatine Creatine An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. Acute Kidney Injury:
  • Data are limited.
  • May provide a modest benefit to help slow progression
• Exon-skipping therapy:
  • Novel therapeutic approach in genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics with unproven clinical benefits
  • Works like “molecular patches Patches Vitiligo” on the abnormal DMD gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics
  • Allows for the production of a more functional (but not entirely normal) dystrophin Dystrophin A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. Blotting Techniques protein
  • Options: eteplirsen, golodirsen, and viltolarsen

Interventions

• Surgery indicated for tendon release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology in contractures Contractures Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint. Wound Healing
• Treatment of scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis
• A feeding tube may be considered for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with significant dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia.
• Tracheostomy Tracheostomy Surgical formation of an opening into the trachea through the neck, or the opening so created. Laryngomalacia and Tracheomalacia for ventilator support may be considered in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure.

Close surveillance Surveillance Developmental Milestones and Normal Growth

• Evaluation and monitoring of cardiomyopathy Cardiomyopathy Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease). Cardiomyopathy: Overview and Types:
  • ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG)
  • Echocardiogram Echocardiogram Transposition of the Great Vessels or cardiac MRI Cardiac MRI Imaging of the Heart and Great Vessels
• Respiratory management includes:
  • Monitoring of vital capacity Vital capacity The volume of air that is exhaled by a maximal expiration following a maximal inspiration. Ventilation: Mechanics of Breathing using pulmonary function test Pulmonary function test Pulmonary function tests are a group of diagnostic procedures yielding useful, quantifiable information about the rate of the flow of air through the individual’s airways, lung capacity, and the efficiency of gas exchange in relation to time. The most commonly utilized tests include spirometry (before and after bronchodilator use), lung volumes, and quantitation of diffusing capacity for carbon monoxide (CO). The tests can be influenced by the individual’s effort/fatigue, disease state, or anatomical malformation. Pulmonary Function Tests
  • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep study with capnography

Palliative care and advanced planning

• Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship and families should be informed of the long-term prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas.
• Address end-of-life issues End-of-life issues The end of a patient’s life has been a difficult, complex, and often controversial aspect of medicine, because, historically, death has been conceptualized as a “failure” on the physician’s part. As our understanding of death has evolved, so has the physician’s relationship to it, becoming a companion to the patient in their final moments. Moreover, experienced doctors understand that during the last days of a person’s life, the focus must be on maximizing quality of life rather than on prolonging it. End-of-life Issues.
• Palliative measures can be used at any point in the disease.

Complications

• Cardiac:
  • Cardiac muscle Cardiac muscle The muscle tissue of the heart. It is composed of striated, involuntary muscle cells connected to form the contractile pump to generate blood flow. Muscle Tissue: Histology fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans leads to: 
    • Dilated cardiomyopathy Cardiomyopathy Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease). Cardiomyopathy: Overview and Types
    • Conduction abnormalities and arrhythmias
  • Cardiac complications are the most common cause of death.
• Respiratory:
  • Progressive impaired pulmonary function results from: 
    • Weak chest-wall muscles
    • Poor trunk posture from scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis and lordosis
  • Assisted ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing is eventually required.
  • Increased risk for pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
• Orthopedic:
  • Fractures secondary to falls
  • Contractures Contractures Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint. Wound Healing
• GI:
  • Dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia
  • Constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
• Neurocognitive:
  • Intellectual disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment is common.
  • Increased association with: 
    • Autism
    • ADHD ADHD Attention deficit hyperactivity disorder is a neurodevelopmental disorder characterized by a pattern of inattention and/or hyperactivity-impulsivity that occurs in at least 2 different settings for more than 6 months. Although the patient has normal intelligence, the disease causes functional decline. Attention Deficit Hyperactivity Disorder
    • OCD OCD Obsessive-compulsive disorder (OCD) is a condition characterized by obsessions (recurring and intrusive thoughts, urges, or images) and/or compulsions (repetitive actions the person is compelled to perform) that are time-consuming and associated with functional impairment. Obsessive-compulsive Disorder (OCD)
    • Anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder

Differential Diagnosis

• Becker muscular dystrophy Becker muscular dystrophy Becker muscular dystrophy (BMD) is an X-linked recessive genetic disorder that is caused by a mutation in the DMD gene. Abnormal, partially functional muscle dystrophin protein is produced, which leads to progressive muscle weakness and the eventual loss of ambulation. Becker Muscular Dystrophy (BMD): 2nd most common form of muscular dystrophy Muscular Dystrophy Becker Muscular Dystrophy. Becker muscular dystrophy Becker muscular dystrophy Becker muscular dystrophy (BMD) is an X-linked recessive genetic disorder that is caused by a mutation in the DMD gene. Abnormal, partially functional muscle dystrophin protein is produced, which leads to progressive muscle weakness and the eventual loss of ambulation. Becker Muscular Dystrophy can result from an X-linked X-linked Genetic diseases that are linked to gene mutations on the X chromosome in humans or the X chromosome in other species. Included here are animal models of human X-linked diseases. Common Variable Immunodeficiency (CVID) recessive mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in the DMD gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics. Becker muscular dystrophy Becker muscular dystrophy Becker muscular dystrophy (BMD) is an X-linked recessive genetic disorder that is caused by a mutation in the DMD gene. Abnormal, partially functional muscle dystrophin protein is produced, which leads to progressive muscle weakness and the eventual loss of ambulation. Becker Muscular Dystrophy is less severe than DMD, resulting in a later onset of symptoms, slower clinical progression, and longer life expectancy Life expectancy Based on known statistical data, the number of years which any person of a given age may reasonably expected to live. Population Pyramids. Creatine kinase Creatine kinase A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: the mm type from skeletal muscle, the mb type from myocardial tissue and the bb type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. Skeletal Muscle Contraction levels are less elevated and intellectual disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment is uncommon in BMD. Confirmation is with genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies. Muscle biopsy Muscle Biopsy Trichinella/Trichinellosis shows sparing of muscle fibers. Dystrophin Dystrophin A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. Blotting Techniques can be visualized using immunostaining. Management is supportive.
• Facioscapulohumeral muscular dystrophy Muscular Dystrophy Becker Muscular Dystrophy: an autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance disorder resulting from mutations in DUX4 or SMCHD1 genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure. Both boys and girls are affected. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with progressive weakness of facial, scapular, and muscles of the upper arm Arm The arm, or “upper arm” in common usage, is the region of the upper limb that extends from the shoulder to the elbow joint and connects inferiorly to the forearm through the cubital fossa. It is divided into 2 fascial compartments (anterior and posterior). Arm: Anatomy by 20 years of age. Cardiac involvement is rare. There is a modest elevation in CK and the diagnosis is confirmed by genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies. Management is supportive.
• Limb-girdle muscular dystrophy Muscular Dystrophy Becker Muscular Dystrophy: a group of myopathic disorders resulting from varying genetic defects. Both boys and girls are affected. The time of onset for the disease varies and is characterized by slowly progressive atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation and weakness of the proximal muscles of the hip and shoulder. Cardiac disease is not typical. Diagnosis of limb-girdle muscular dystrophy Muscular Dystrophy Becker Muscular Dystrophy is confirmed by genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies. Management is supportive.
• Myotonic dystrophy: a group of autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance disorders that can affect Affect The feeling-tone accompaniment of an idea or mental representation. It is the most direct psychic derivative of instinct and the psychic representative of the various bodily changes by means of which instincts manifest themselves. Psychiatric Assessment multiple systems. Myotonic dystrophy can be congenital Congenital Chorioretinitis or adult onset. Findings include myotonia Myotonia Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of myotonic disorders. Ion Channel Myopathy, distal and facial muscle wasting, cataract Cataract Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). Neurofibromatosis Type 2, intellectual disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment, and endocrine disorders. The diagnosis is based on genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies, and management is mainly supportive.
• Emery-Dreifuss dystrophy: a genetic disease with various modes of inheritance. Emery-Dreifuss dystrophy is characterized by slowly progressive weakness of the upper arms and lower legs, contractures Contractures Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint. Wound Healing, and cardiac abnormalities in the 1st or 2nd decade of life. Modestly elevated CK may be seen. Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies is used to confirm the diagnosis. Management is supportive, and most individuals do not lose the ability to ambulate.
• Spinal muscular atrophy Spinal Muscular Atrophy Spinal muscular atrophy (SMA) is a spectrum of autosomal recessive syndromes characterized by progressive proximal muscle weakness and atrophy, possibly due to degeneration of the anterior horn cells in the spinal cord and motor nuclei in the lower brainstem. Spinal Muscular Atrophy: a group of autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance disorders leading to degeneration of the anterior horn Anterior horn One of three central columns of the spinal cord. It is composed of gray matter spinal laminae VIII and ix. Brown-Séquard Syndrome cells of the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy and brainstem. The clinical presentation of spinal muscular atrophy Spinal Muscular Atrophy Spinal muscular atrophy (SMA) is a spectrum of autosomal recessive syndromes characterized by progressive proximal muscle weakness and atrophy, possibly due to degeneration of the anterior horn cells in the spinal cord and motor nuclei in the lower brainstem. Spinal Muscular Atrophy varies. More severe forms of spinal muscular atrophy Spinal Muscular Atrophy Spinal muscular atrophy (SMA) is a spectrum of autosomal recessive syndromes characterized by progressive proximal muscle weakness and atrophy, possibly due to degeneration of the anterior horn cells in the spinal cord and motor nuclei in the lower brainstem. Spinal Muscular Atrophy present in infancy to early childhood with progressive weakness, muscle atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation, gross motor Gross Motor Developmental Milestones and Normal Growth delay, tongue Tongue The tongue, on the other hand, is a complex muscular structure that permits tasting and facilitates the process of mastication and communication. The blood supply of the tongue originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation and fasciculations Fasciculations Involuntary contraction of the muscle fibers innervated by a motor unit. Fasciculations may be visualized as a muscle twitch or dimpling under the skin, but usually do not generate sufficient force to move a limb. They may represent a benign condition or occur as a manifestation of motor neuron disease or peripheral nervous system diseases. Polyneuropathy, dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia, and respiratory insufficiency. Diagnosis is confirmed based on genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies. Management is supportive, and life expectancy Life expectancy Based on known statistical data, the number of years which any person of a given age may reasonably expected to live. Population Pyramids varies by the disease type.