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