Duchennes Muscular Dystrophy

Duchennes Muscular DystrophyGroup A4Khalil Ali, Mollie Auguste, kajan devamanoharan, Neelima Kaushal, Presented by: Joy moore, Nickson Omboro X-Linked Recessive XYXX*XYXX*XXXYXXXYX*YXXXX*XXXYX*YXXXXXX*Intro & Background: 1min2HistoryFirst described by Giovanni Semmola in 1834, and Gaetano Conte in 1836Named after Guillaume Duchenne for his description, live tissue samples, and case photos in his 1862 Album de Photographies PathologiquesMoral of the Story: take very good notes, lots of pictures, and PUBLISHHistory: 0.5-1min3SymptomsAs early as 1 year old, early motor milestones may be met, but often walking is delayed5 years old, initial proximal limb muscle weakness. Muscle wasting, difficulty running. Gowers sign Waddling duck-like gaitLater compensatory hypertrophy of distal sites, such as the calf muscles, followed eventually by pseudohypertrophy with increased fibrous tissue and adipose tissue replacing muscles.

Symptoms: 1-2mins4DiagnosisBlood: Increased serum CK-MMLight Microscopy: random variation in muscle fiber size, necrosis of individual muscle fibers, and replacement of necrotic fibers by fibrofatty tissue invaded by histiocytes. Immunochemical Staining: absence of dystrophinConfirmatory Muscle Biopsy: characteristic rounded, enlarged fibers without normal cross-striations, fiber necrosis, regeneration and replacement by fat and hyalineDegenerative and regenerative changes in adjacent myocytesDiagnosis: 1min5CauseMutation in Xp21, mostly deletion mutation, the rest are frameshift and point mutationsCan affect any segment of the Dystrophin geneThe given mutation will be constant within families and gives characteristic DNA codingDeficiency of Dystrophin synthesis, a 427kDa protein Dystrophin normally present in small amounts in the sarcolemmaActin-binding transmembrane proteinStabilizes the sarcolemma and acts as a link between the cytoskeleton and ECMTargets skeletal muscle tissue, but it may also affect cardiac muscle

Cause 1min6Worldwide PrevalenceX-linked recessive, with up to 2/3 as familial cases, and 1/3 resulting from de novo mutation. Occurs almost entirely in male children, though possible in females1 : 3,500 infant malesMost common and most severe of the muscular dystrophiesTreatment & Management Prognosis: grim outlook, death usually before age 20Wheelchair dependent by age 10-12 years oldPelvic & shoulder girdle weakness and ataxia progressing to immobilization, wasting, muscle contracture, heart failure, arrhythmiasDeath in early teens, most often due to pneumonia from respiratory insufficiency Female carriers are clinically asymptomatic, but have elevated CK and risk developing dilated cardiomyopathy later in lifeManagement Goals: protect cardiac muscles and provide respiratory support

Future PerspectivesPrimarily Longitudinal Research and observational studiesDrug Tolerability & Off-label Efficacy studies in Phases 1 & 2Myoblast Transplant study now recruiting for Phases 1 & 2Obstacle: how to introduce a single large gene targeted into all muscle cells without initiation of an immune response to the new gene productResourceshttps://www.genome.gov/19518854https://www.mda.org/ Antthony, Douglas, & Matthew Frosch & Umberto de Girolami. 27: Peripheral Nerve & Skeletal Muscle Robbins & Cotran Pathology, ed 7.Smith C., Marks A., Lieberman M. Mark's Basic Medical Biochemistry - A Clinical Approach, 2004.https://www.nlm.nih.gov/medlineplus/ency/article/000705.htmReesieCup93. Cole Getting Up Using Gowers, YouTube, 2008.