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)
Cleft lip and palate manifestations and treatment
> Manifestations Vary (size, involvement of teeth, uni/bilateral) Cleft palate: difficulty feeding Difficulty vocalizing/speech > Treatment Lactation consultant Plastic surgery 3 months to close lip 1 year to close palate Dental/Orthodontia work Speech therapy
Down syndrome (trisomy 21) and risk factors
Most common chromosomal disorder (1/733 births)
Error in cell division during meiosis resulting in trisomy of chromosome 21
UKE; aged oocyte
Obvious manifestations at birth
> Risk Factors
Increases with maternal age (sharp rise @ 30)
1/25 births after 45 years of age
Also a form of Downs that has no relation to maternal age (5%)
Environmental agents (chemicals, radiation, drugs)
Down syndrome manifestations
> CNS Mental retardation Increased risk of Alzheimer disease > Head/face small, square skull Flat facial profile, small nose, depressed nasal bridge Eyes: slant upwards, epicanthal fold Ears: small, low-set, malformed Tongue: large protruding (open mouth)
Down syndrome manifestations con’t…
> Skeletal Retarded growth Hands: short, fingers curled inward, single palmar crease (simian crease) Large space between large & second toe Hypotonia, joint laxity Fat pad on back of neck > CVS - Congenital heart defects > GI malformations > Acute Leukemia
Turner syndrome and manifestations
All or part of X chromosome is absent Results in a variation of manifestations in females > Manifestations - Sexual Lack ovaries (no menstruation) Lack secondary sex characteristic - CNS visual/spatial disorganization Difficulty driving , doing math, psychomotor skills, focusing strabismus
Turner syndrome and manifestations con’t…
> Skeletal
- Short, with normal body proportions
- Deformed nail growth; short 4th metacarpal
CVS
Congenital heart defects (coarctation of aorta, aortic valve deformities)
Altered vascular supply to kidney (displacement)
Integument
Neck webbing
Multiple pigmented nevi
Lymphedema of hands/feet
Turner syndrome diagnosis and treatment
> Diagnosis
Often not noted until late childhood or early adolescence
Treatment
- Growth hormone estrogen therapy
Klinefelter Syndrome
At least one extra X chromosome in male (XXY)
Often undetected at birth except for
Small penis
Small, firm testicles
Klinefelter Syndrome manifestations
Gynecomastia
Sparse facial and body hair
Small testes (don’t respond at puberty to androgens)
inability to produce sperm
Tall stature at puberty d/t low testosterone levels (lower body longer than upper)
Female distribution of fat later in life
Genetic Disorders d/t Environmental Influences
General Maternal Factors
- Teratogenic Factors ( producing abnormalities during embryonic or fetal development) - Ionizing Radiation - Chemicals - Drugs
Genetic Disorders d/t Environmental Influences general maternal factors
General Maternal Factors Hormonal balance State of health Measles can cause malformations DM Nutritional status Medications/drugs
Ionizing radiation
- Teratogenic and mutagenic
- Possibly effecting inheritable genetics
- No evidence of diagnostic procedures being dangerous
- Possible damage with diagnostic radioactive iodine during 13th week of gestation when thyroid gland developing
- Microcephaly
- Skeletal malformations
- Mental retardation
Chemicals and drugs properties and dependent on…
Properties
- Cytotoxic , anti-metabolic, growth inhibiting
Dependent upon
Time of exposure (embryonic/fetal development)
Length of exposure (time)
Extent of exposure (dosage)
Type of chemical/drug
Lipid- soluble will cross placenta more easily
Small molecular weight cross more easily
Chemicals and drugs con’t…
Alcohol Smoking : low birth weight Mercury: defects, blindness Anticoagulants Anticonvulsants Anti-cancer agents Vitamin A Accutane (used to treat acne) Tetracycline Thalidomide (used to be given for nausea during pregnancy but cause birth deformities)
Fetal alcohol syndrome
Alcohol is lipid-soluble, moderate molecular weight
Passes freely across placental barrier
Results in concentration just as high in fetus as in mother
Effects dependent on time/amount
Prenatal and/or postnatal growth retardation
> CNS abnormalities
- Developmental & intellectual delays
> Characteristic facial features
Growth deficits
Folic acid deficiency
Implicated in development of neural tube defects of brain, spine, spinal cord Anencephaly Spina bifida 400ug/day recommended during pregnancy Dietary sources Cereals Orange juice Dark leafy greens, vegetables, legumes
Infectious agents
TORCH
> Toxoplasmosis
Parasite infection from raw/poorly cooked meat, domestic cat feces resulting in CNS symptoms
Mother to fetus transmission
> Rubella
Remains endemic in some developing countries
Mother infected in first 20 weeks of pregnancy = defects
> Cytomegalovirus
- Can lead to retardation e.g. Epstein barr
> Herpes simplex virus type 2
