Genetic & Congenital Disorders Flashcards
What is a genetic disorder?
> Discrete event that affects gene expression in a group of cells related to each other by gene linkage
- Genetic factors (single or multi gene disorder or chromosomal abnormality)
- Environmental factor during embryonic or fetal development (maternal disease, infection, drugs taken during pregnancy)
- May show up as birth defects or later as congenital disorders… or…
Acquired d/t toxin(s)
What is the difference between a genotype and phenotype?
Genotype: is the genetic composition
Phenotype: is the observable expression of genotype
Compare autosomal recessive and autosomal dominant
> Autosomal dominant
Each child has a 50% chance of inheriting the disorder
Only need to get the abnormal gene from one parent
Autosomal recessive
Each child has a 25% chance of being affected, 25% chance of being un affected, and 50% chance of being a carrier
Need 2 copies of abnormal gene to be affected
What is Marfan syndrome?
> Autosomal dominant (1/20,000)
Familial in 75%; rest are result of a mutation in parent’s lifetime
Affects fibrillin I, a component of extracellular matrix resulting in:
- Decreased maintenance of tissue architecture of body structures such as….tendons, heart valves, blood vessels, ocular organs (eyes).
Marfan syndrome manifestations (skeletal & Ocular)
> Skeletal
- Long limbs, fingers
- Hyper-extensible joints
- Kyphosis, scoliosis
- Pectus excavatum (deeply depressed sternum) aka pigeon chest
Ocular
- Bilateral dislocation of lens (d/t weak ligaments)
- Myopia with predisposition to retinal detachment
Marfan syndrome manifestations cont’d…(cardiovascular)
Cardiovascular
Mitral valve prolapse
Progressive dilation of aortic valve ring
Weak aorta and other arteries (dissection, rupture)
Increased risk of dissection during pregnancy!
What is Neurofibromatosis?
> Neurogenic tumors arising from Schwann cells in peripheral nervous system
Result of defect in tumor-suppressor gene
Type NF-1 (Recklinghausen disease)
Type NF-2
NF-1 Recklinghausen Disease & manifestations
- Autosomal dominant (50% familial, 50% new mutation)
> Manifestations - Neural tumors (neurofibromas) on body
- Often erupt at puberty
- Soft, pink lesions projecting from skin
- Firm, round, can be painful
- Café au lait spots = birth marks
- Flat, brown/light brown
- Sharply demarcated edges
NF-1 Recklinghausen manifestations cont’d…
> Manifestations (cont)
- Lisch nodules on iris
- Often appear at 6 years of age
- Often no problems
- Scoliosis
- Learning difficulties
- Epilepsy
- Vision problems
What is type NF2
- Acoustic nerve tumors
- Multiple intracranial & spinal meningiomas near cranial nerve VIII
- Auditory-vestibular nerve
- Asymptomatic for first 15 years
> Manifestations - headaches, hearing loss, tinnitus
- Exacerbated by pregnancy and oral contraceptives
Phenylketonuria (PKU)
- Autosomal recessive disorder
(both parents must have gene) - Elevation of phenylalanine
- Amino acid obtained via diet
- Usually converted to tyrosine by liver enzyme
If enzyme lacking = PKU - Tyrosine assists neurotransmitters and melanin synthesis.
Phenylketonuira manifestations & treatment
> Manifestations
May appear normal at birth; symptoms appear in a few weeks but too late as CNS damage has occurred
Musty odor to sweat/urine
Light skin and hair, eczema
Microcephaly, mental retardation, seizures
Treatment
Dietary supplements must being invitro to prevent mental retardation… “diet for life”
Enzyme replacement being developed
Tay Sachs Disease
Rare autosomal recessive genetic disorder
Eastern European Jewish population (high carrier rate)
Accumulation of gangliosides in the lysosomes of all organs, predominantly brain and retina neurons
Results in destruction of neurons
Diagnostic
Cherry-red spot on macula
Tay sachs disease manifestations
> Manifestations
- Infants appear normal at birth
- Progressive weakness, muscle flaccidity appearing at approximately 6 months of age
- Decreased attention span
- Rapid deterioration of motor & mental function, often with generalized seizures after approx. 10 months
- Visual impairment and eventual blindness
- Death by 4-5 years (no cure or treatment)
Cleft lip and palate and causes
Common birth defect/ conspicuous (1-2/1000 births)
Boys > girls (lip and palate)
Isolated cleft palate more common in girls
Develops at 35 days gestation
> Etiology
- Heredary
- Environmental
- Teratogens (rubella, anticonvulsant medications)
