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Marfan syndrome pathophys
-Autosomal Dominant disorder
-Effects CT; missense mutations in FBN 1 gene on chromosome 15
encodes protein called fibrillin = without this, tissues are weakened
Signs of Marfan Syndrome
1. Tall Stature
2. Arachnodactyly
3. Ectopia lentis: dislocation of the lens
4. Weak aortic wall - Aortic Root dilation
-Dissecting aortic aneurysm
5. Mitral valve prolapse: does not close properly due to widened atria
6. High arched palate
7. Pectus Deformities (Concave sternum)
8. Loose/weak tendons, ligaments, joint capsules
What could weak tendons, ligaments, and joint capsules lead to in Marfan syndrome?
-Hyperextensibility of joints
-dislocations
-hernias
-kyphoscoliosis
Tx of Marfan Syndrome
-no cure
-avoid strenuous activities (prevents AA, or lose joints)
-Annual slit lamp eye exams
-Eval skeletal growth for scoliosis
-Endocarditis prophylaxis (bc of valve dysfunction)
What is the most feared complication of Marfan syndrome?
Aortic Dissection
*require ECG annually to monitor aortic diameter and mitral valve function)
When does marfan syndrome aorta need surgery
diameter around 50-60 mm
Prognosis of mar fan syndrome
Untreated: men die in 30s, women die in 40s

Treated: life expectancy normal
Ehlers-Danlos Syndromes Classification
Disorders of connective tissue
*hyperelastisity, fragility of skin
---trivial injuries could become serious wounds
---sutures don't hold well
*joint hypermobility
*bleeding diathesis
---spontaneously rupture large blood vessels, bowel and gravid uterus
Most Genetic Metabolic Diseases are:
Autosomal recessive
Autosomal Recessive Diseases: usual to find affected individuals in ____
the same generations; horizontal pattern of inheritance
Characteristics of X-linked dominant inheritance
1. Never passed from father to son
2. All daughters of an affected male and a normal female are affected
3. All sons of an affected male and normal female are NORMAL
Males vs. females in X linked traits
Males: more severely affected than females (lethal maybe)

Females: More likely to be affected than males
Vitamin D-independent rickets
X linked dominant inheritance
X linked recessive disorders characteristics
1. Trait is seen in males bc they are hemizygous
2. females are heterozygous carriers

most X linked traits are recessive
Duchenne's Muscular Dystrophy
Gene for DMD is found on X chromosome and encodes large protein: Dystrophin
required inside muscle cells for structural support
-without it, cell membrane is permeable, and so things get inside, pressure increases, and muscle cell explodes
_immune response adds to damage
DMD Signs
-Normal early childhood
-age 3-5 - gait becomes clumsy
-progressive proximal muscle weakness
Spreading of weakness in DMD
Progressive proximal muscle weakness

1. Early 2nd decade - wheel chair bound
2. Eventually spreads to arms, neck, other areas
Early signs of DMD
1. Pseudohypertrophy
-enlargement of calf and deltoid muscles
2. low endurance
3. difficulty in standing without help or walking up stairs
Gower's sign
Pt. pushes themselves erect by moving hands up their thighs
Lab results for DMD
Elevated CK levels
(destruction of cells)
Muscle biopsy - degeneration and regeneration
Tx for DMD
No cure
Control pt sx
PT, OT speech, recreational therapy

focus on pulmonary function, aspiration, respiratory muscles
-can do surgical release of muscular contractures
Prognosis of DMD
Most die from respiratory insufficiency or cardiac failure by 2nd or 3rd decade
Becker Muscular Dystrophy
Dystrophin is present, but not enough of of
*less severe than DMD

X linked recessive
Clinical distinction between DMD and BMD
Less severe muscle weakness in BMD
Affected maternal uncles with BMD continue to be ambulatory after age 15-20
Clinical presentation of BMD
-Delayed gross motor milestones "clumsy"
-increased falling, toe walking, hard rising form floor
-proximal muscle weakness
-dilated cardiomyopathy can be first sign
-Gower Sign
-Progressive, symmetrical muscle weakness (quads might be only)
-Pseudohypertrophic calves
First sign of BMD
Can be cardiomyopathy
What is a big differential between BMD and DMD
BMD preserves the neck flexor muscle strength
Lab Analysis for BMD
Elevated Serum CK (mod to severe0
Dystrophin gene deletion
Muscle biopsy with dystrophin antibody
Tx for BMD
No cure
Therapy: PT, OT, rec, thpy

Complications: cardiac, respiratory, aspiration
Prognosis of BMD
Death from respiratory or cardiac failure

Mean age is 42 (longer than DMD)
Most common Cause of intellectual disability
Trisomy 21
Mechanisms responsible for Trisomy 21
1. Nondisjunction in the first meiotic division (correlates with older maternal age)
2. Translocation
3. Mosaicism
Dx of Down Syndrome
At birth by observation and confirmed by cytogenic analysis
Signs at birth of Trisomy 21
Hypotonia
Brachycephaly
Upslanting palpebral fissure
Brushfields spots (in light eyed)
Flat nasal bridge with underdvp mid face
Simian crease
Small low set ears and protruding tongue
Down syndrome becomes what other disease
Alzheimers
*can see alzheimers disease around age 35
Life expectancy of down syndrome
First decade of life: presence or abcesnse of heart defect dictates survival

20 years or more less than general population

Age 52-54 death

Bye age 70 only 10% still alive
Trisomy 18
more rare than trisomy 21
Spontaneous abortion in 95% of cases
Mortality rate in first 48 hours is over 50%
Identification of trisomy 18
1. Significant on IUGR (inter uterine growth restriction)
2. Omphalocele
-protrusion of abdominal contents through umbilicus
3. Esophageal atresia
Trisomy 13
Almost all die in immediate neonatal period
Bilateral cleft lip and palate
Congenital heart disease
Microphthalmia - small eyes
CNS defects
Bulbous nasal tip
Polydactylyl
Cri du Chat syndrome cause
short arm deletion of 5th chromosome
Cri du chat signs
1. high pitched cry similar to mewing cat (decreases with age)
2. Microcephaly
3. Hypertelorism (increased distance between eyes)
4. slow postnatal growth
5. mental deficiency
Lyon Effect
One X is irreversibly inactivated early in embryogenesis
(either paternal or maternal)
Extra X chromosomes
The amount of X chromosomes correlates with mental disability
Klinefelter Syndrome
47, XXY

One or more X chromosomes in excess of normal Male XY complement

50% lost spontaneous abortion

Incidence: same as trisomy 21
Klinefelter syndrome mechanism
Meiotic nondisjunction during gametogenesis
Klinefelter syndrome pathology
1. initially - intrinsically abnormal testes do not respond to stimulation by gonadotropins
2. low testosterone and elevated LH
Dx of klinefelter syndrome
-not until after puberty
-normal testicular growth and masculinazion do not occur (remain small)
-azoospermia results in infertility
-high pitched voice
-female pattern of hair
-gynecomastia
-childhood and psych problems
-tall and thin
Turner Syndrome (45,X)
XO-girl

Alteration on the ovary of women with Turners represent an acceleration in aging of the ovary

Oocytse die off by age 2, converted to fibrous streaks
Turners syndrome signs
-short
-infertility with gonadal dysgenesis (no longer makin eggs)
-infreased fx of renal/cardiac anomalies
--coarctation of aorta
-laterally protruding ears, uplifted lobules
-lower canthal folds
-neck webbing
-lower posterior hairline
Tx of turners
Tx with growth hormone and estrogen and enjoy a great prognosis for normal life
-infertile but can give estrogens to help them dvp normally