Fandom

Psychology Wiki

Genetic counseling: Becker Muscular Dystrophy

34,203pages on
this wiki
Add New Page
Talk0 Share

Assessment | Biopsychology | Comparative | Cognitive | Developmental | Language | Individual differences | Personality | Philosophy | Social |
Methods | Statistics | Clinical | Educational | Industrial | Professional items | World psychology |

Clinical: Approaches · Group therapy · Techniques · Types of problem · Areas of specialism · Taxonomies · Therapeutic issues · Modes of delivery · Model translation project · Personal experiences ·


Becker Muscular Dystrophy

General InformationEdit

  • Dystrophinopathies
    • Characterized by a spectrum of muscle disease that ranges from mild to severe
    • Duchenne/Becker muscular dystrophy is severe
      • Skeletal muscle is primarily affected in both
      • DMD is rapidly progressive and presents in early childhood.
        • Patients are often wheelchair-bound by age 12
      • Becker is characterized by later-onset skeletal muscle weakness
        • Patients remain ambulatory into their 20s
        • Despite milder skeletal muscle involvement, heart failure from dilated cardiomyopathy is a common cause of morbidity and the most common cause of death
        • Mean age of death is in the mid-40s
  • Dystrophin gene
    • Xp21.2
    • Encodes protein dystrophin
    • 85% of males with BMC have deletions or duplications involving exons of this gene
    • Molecular genetic testing is available clinically
  • Prevalence
    • 1 in 18,000 live male births

DiagnosisEdit

  • Clinical
    • Family history
      • Compatible with X-linked recessive inheritance
    • Creatine Phosphokinase (CK) concentration
      • Evaluated by blood test
      • Elevated serum CK concentration results from progressive elimination of dystrophic muscle fibers.
        • Can also result from strenuous exercise
      • CK concentration gradually decreases with advancing age due to the progressive elimination of these muscle fibers.
      • 100% of males with BMD have a serum CK concentration >5x normal
      • ~30% of female carriers have a concentration 2-10x normal
        • Some investigations have shown a wide variability in BMD carriers
        • Many have levels within the normal range, so other tests are necessary
        • CPK is not completely reliable
    • Clinical findings
      • Progressive symmetrical muscle weakness and atrophy, proximal greater then distal, often with calf hypertrophy
        • Weakness of quadriceps femoris may be the only sign
      • Activity-induced cramping in some patients
      • Flexion contractus of the elbows may occur late in the course
      • Wheelchari dependency, if present, after 16 years of age
      • Preservation of neck flexor muscle strength in BMD differentiates it from DMD
  • Molecular genetic testing
    • Deletions involving one or more exons of the DMD gene
      • ~85% of males with BMD have deletions
      • Testing is done by PCR or southern blot
      • Available on a clinical basis
    • The remaining ~15% have duplications of one or more exons of the DMD gene or other mutations such as small deletions or insertions, single base changes, or splicing mutations
    • Carrier testing may be performed but requires quantitative analysis for gene dosage which can be difficult to perform and interpret
    • Prenatal testing is available

Clinical DescriptionEdit

  • Males
    • Characterized by later-onset skeletal muscle weakness (as compared to DMD which presents ~ age 4 years)
      • Patients remain ambulatory into their 20s with BMD
    • Heart failure from dilated cardiomyopathy is a common cause of morbidity and the most common cause of death
    • The mild end of the spectrujm includes men with onset of symptoms after age 30 years who remain ambulatory even into their 60s
    • Cognitive impairment is not as common or as sever as in DMD
  • Females
    • Occasionally have clinical features as the result of X chromosome rearrangements involving the DMD locus (Xp21.2)
    • 81% of BMD carriers have no signs or symptoms
    • 14% have mild to moderate muscle weakness
    • 16% have left ventricle dilation
    • 5% have myalgia or cramps
    • No BMD carrier females have been found to have dilated cardiomyopathy
  • Genotype-Phenotype Correlations
    • In males, phenotypes are best correlated with the degree of expression of dystrophin, which is largely determine by the reading frame of the spliced messaged obtained from the deleted allele
    • The BMD phenotype occurs when there is some dystrophin, usually resulting from:
      • Deletions or duplications that juxtapose "in-frame" exons
      • Some splicing mutations
      • Most non-truncating single base changes that result in translation of a protein product with intact N or C termini
    • A dystrophin protein that retains partial function produces the milder BMD phenotype
  • Management
    • There is no treatment for BMD
    • Appropriate management can prolong survival and improve quality of life
      • Physical therapy to promote mobility
        • Range-of-motion exercises
      • Braces to delay the onset of contractures
      • Monitoring and surgical intervention for orthopedic complications
        • Scoliosis, kyphosis, or lordosis
      • Routine monitoring for evidence of cardiomyopathy
    • All carriers should have a complete cardiac evaluation at least once

Differential DiagnosisEdit

  • Limb-girdle muscular dystrophy
    • A group of disorders clinically similar to DMD
    • Occurs in both sexes
    • Caused by mutations I genes that encode sarcoglycans and other proteins that interact with dystrophin
  • Emery-Dreifuss muscular dystrophy
    • Associated with limb contractures and cardiac arrhythmia
  • X-linked recessive, autosomal dominant, and autosomal recessive forms
    • Caused by mutations in the LMNA gene
  • Spinal muscular atrophy
    • Caused by mutations in the SMN gene
    • Characterized by:
      • Poor muscle tone
      • Symmetric muscle weakness that spares the face and ocular muscles
      • Evidence of anterior horn cell involvement
        • Includes fasciculations of the tongue and absence of deep tendon reflexes
  • Dilated cardiomyopathy
    • Can be sporadic or familial
  • No other phenotypes are associated with mutations in the DMD gene

InheritanceEdit

  • X-linked recessive
    • Carrier females have a 50% chance of transmitting the BMD mutation in each pregnancy
    • With each pregnancy, a carrier has a 25% chance of having an affected child
  • Risk to family members
    • A woman with an affected son and one other affected relative in the maternal line is an obligate heterozygote
    • A woman with more than one affected son and no other family history can have:
      • A germline mutation
        • DMD disease-causing mutation present in every cell
      • Germline mosaicism
        • Mosaicism for a DMD disease-causing mutation which includes the germline
        • The frequency of germline mosaicism in DMD is estimated at 12% to 20%
    • If proband is only affected family member, must determine if mother and other females are carriers
      • The proband may have a de novo DMD disease-causing mutation
        • The mutation could have occurred in the egg at the time of conception
        • The mutation could have occurred after conception and therefore is present in some but not all cells of the proband's body.
        • The likelihood that the mother is a carrier is low
      • The proband's mother may have a de novo mutation
        • 2/3 of mothers of sporadically occurring males with DMD are carriers
        • Could have occurred if:
          • Mutation occurred in the egg or sperm at the time of her conception and is present in every cell of her body (germline mutation)
          • Mutation is present in some but not all cells of her body (somatic mosaicism)
          • Mutation is present only in her egg cells (germline mosaicism) and is not detected in a blood sample.
      • The proband's mother may have inherited a DMD mutation from her mother who is a carrier, her mother or father who has somatic mosaicism, or her mother or father who has germline mosaicism.

Risk AssessmentEdit

  • All daughters of a male affected with BMD are carriers; none of the sons will inherit the mutation

Ordering the testEdit

  • Patient must sign consent form for DNA analysis
    • Use blue ink so it is obvious which is the original
    • Give the patient a copy
    • Put the original in the chart
  • Use special specimen processing request form
    • Make a copy for the chart
    • Give a copy to Lori Martineek at E352
  • Blood is drawn at Test Referral Center
    • Pt must have consent form, 2-ply specimen processing request form, and DNA analysis requisition
    • Tell pt to make sure her name is on the tube of blood
    • TRC will FedEx to Dr. Prior's lab
  • Contact Dr. Thomas W. Prior to inform him that you are sending the sample
    • Prior-1@medctr.osu.edu
    • Give him clinical history and lab report # from prior testing

ResourcesEdit

  • Muscular Dystrophy Association
    • 800-572-1717
    • [1]

ReferencesEdit

  • Emery and Rimoin's Principles and Practice of Medical Genetics. Third Edition, 1996. pp 2337-2354
  • National Organization for Rare Disorders (NORD)
  • Nelson's Textbook of Pediatrics. 15th Edition. pp1745-1748
  • Online Mendelian Inheritance in Man (OMIM). BMD#300376
  • [www.geneclinics.org] (GeneReviews)

NotesEdit

The information in this outline was last updated in 2002.


Material obtained under GFDL Licence from http://en.wikibooks.org/wiki/Handbook_of_Genetic_Counseling

Heckert GNU white Permission is granted to copy, distribute and/or modify this document under the terms of the GNU Free Documentation License, Version 1.2 or any later version published by the Free Software Foundation; with no Invariant Sections, no Front-Cover Texts, and no Back-Cover Texts. A copy of the license is included in the section entitled "GNU Free Documentation License."

Ad blocker interference detected!


Wikia is a free-to-use site that makes money from advertising. We have a modified experience for viewers using ad blockers

Wikia is not accessible if you’ve made further modifications. Remove the custom ad blocker rule(s) and the page will load as expected.

Also on Fandom

Random Wiki