Dystrophinopath ies Flashcards
Types Albinism
Ocular Albinism:
• Affects only the eyes,
Not the skin or hair.
• Inherited as X-linked disorder
• Mostly in boys
Oculocutaneous Albinism:
• Affects the eyes, hair and skin
• Inherited as autosomal recessive
• Include several forms
• The first form (OCA 1) involves the
tyrosinase enzyme which converts tyrosine
into melanin
Eve abnormalities
Albinism
nystagmus, Photophobia, poor
vision, strabismus, transiucent iris
Dystrophinopathies
Types and gene
• Duchenne muscular dystrophy
Becker muscular dystrophy
a spectrum of X-linked muscle disease
Dystrophin Gene
Locus
Хр21)
X-Linked
79 exons
• The most common mutation are
Dystrophin
The most common mutation are deletions in
65-70%
• Duplications in 7%
Point mutations or small deletions/insertions
in the remainder
Dystrophin
Localized on the
• localized on the intracellular surface of
the sarcolemma along all the lenath of
the myofibers •
Dystrophin It assembles with the……….
For……
dystrophin- associated glycoprotein complex (DGC)
•Stabilizes the fibers during contractions
by to actin B-dystroglycan
Duchenne Muscular Dystrophv
Most severe type
Wasting muscles
• Incidence: males at a rate of 1 in
3,500 births
• The mean age of diagnosis is - 4
years (range: 16 months - 8 years)
• Progressive symmetric muscle weakness (proximal > distal)
Wheelchair bound by age 12 years
Becker Muscular Dystrophy
Milder form
• male births
• Presents later than DMD, between ages /5 and 15 years
• Severity varies among patients
• Wheelchair dependency (after age 16 years) • Some individuals remain ambulatory into their 30s
Clinical Features
Dystrophinopathies
Duchenne
- Gross motor delay - mean age of walking is
approximately 18 months → vegios 12 moths - Gait abnormalities - persistent toe walking, waddling gait
- Difficulty rising from the ground
-Difficulty climbing stairs running, jumpina
-Frequent falls
-Calf muscles: hypertrophic and firm to palpation - Increase in serum CK (creatine phosphokinase) - - -Wheelchair bound by age 12 years
- Learning difficulties in 5% of patients
- Speech problems in 3% of patients
-Cardiomyopathy at 14 to 18 years
-Few patients live beyond 30 years of
age - Reparatory problems and
- cardiomyopathy leading to congestive
heart failure are the usual cause of
death
Diagnosis
Dystrophy
–Serum CK very high
- Serum alanine transaminase and aspartate transaminase levels
-Genetic Testing
-Muscle biopsy
• early in the disease - nonspecific dystrophic changes (variation in fiber size, foci of necrosis and regeneration, inflammatory changes
• later in the disease - deposition of fat and connective tissue
Managemen
Muscular dystrophy, Cardiomyopathy ,Scoliosis:
Cardiomyopathy:
•ACEinhibitor and/or beta
blocker
• diuretics and digoxin are
used as needed
Scoliosis:
bracing
surgery
Muscular dystrophy:
• Corticosteroid:
Prednisone
Deflazacourt
• improve the muscle strength and function
•NOT recommended in children before age two years
• Loss of dystrophin disrupts the DGC
complex, causes
membrane instability
with increased susceptibility to injury,
and fiber necrosis
……… is a common cause of morbidity and mortality
DCM
Reparatory problems and
cardiomyopathy leading to congestive
heart failure are the usual cause of
death
Side effects of Corticosteroid:
• Weight Gain
• Delayed Puberty
• Stunted Growth
• Cataracts
• Osteoporosis
