Neuromuscular Disorders: DMD and BMD
BMD occurrence
1 in 30K males
DMD ocurrence
1 in 3500 boys
DMD muscle progression
1st: trunk, pelvic girdle, and shoulder girdle Hands and feet maintained longers Facial muscles sparedusually
DMD onset
2-4 years
What % of moms of DMD/BMD are carriers?
2/3
DMD lifespan
4th decade Wheelchair before 13y
DMD female carrier CHD risk
5-8% lifetime risk for DCM up to 20% lifetime risk of ventricular dilation
BMD female carrier CHD risk
<1% risk of DCM Up to 15% lifetime risk of left ventricular dilatation
What muscle localization is a/w NMJ?
CMS
What muscle localization is a/w peripheral neuropathies?
CMT spectrum
Largest concern for female carrier for BMD/DMD?
Cardiac function (may be independent of x-inactivation)
First presenting sign of DMD?
Climbing or Towers maneuver
Proximal weakness and stairs
Difficult
Dystrophin mutations
Entire gene deletions rare 60% Exonic del/dup DMD 85-90% exonic del/dup BMD Rest: intragenic mutations (15% DMD mutations --> nonsense, missense very rare)
Dystrophic muscle change
Fatty extra connective tissue
Symptoms of DMD
Generalized weakness and muscle wasting DD: 42% Abnormal gai t(toe walking): 30% Speech delay/ID: 8% Static cognitive impairment: 25-50% (issues with short-term/working memory, issues in executive function) Scoliosis
Gowers maneuver/sign
Gets up by rolling around d/t muscle weakness; can be one-handed Both boys and girls do this; not indicative of a specific diagnosis
Where does DMD impact first?
Hips, pelvic muscles, and thighs first
What else can dbstropinopathy genes cause?
Isolated CM Exercise induced myalgias, muscle cramping
What muscle localization is a/w myopathies/muscular dystrophies?
Muscle
What does Gowers sign indicate?
Proximal muscle weakness
DMD muscle progression direction?
Proximal to distal
What muscle localization is a/w anterior horn cells?
SMA Amyoplasia
When are female carriers of BMD/DMD impacted?
Skewed X-inactivation: 5%of carriers also have weakness (not as severe as males)
Testing for DMD/BMD
Tier 1: test exotic del/dup via MLPA or aCGH Tier 2: full gene seq if NO exonic del/dup
What does primary neuromuscular disorders consist of?
Typically involve: Localization Anterior horn cell diseases PNS: Sensory and/or motor, NM junction, muscle Connective tissue
BMD lfiespan
Varies Wheelchair <16y
Trendelenburg gait
Weakness of abductor muscles of lower extremity, gluteus medium, and gluteus minibus Looks like a waddle
DMD/BMD inheritance
XL
What type of DMD/BMD mutations benefit from exon-skipping treatment?
frame-shift deletions
BMD onset
variable
