what is malformation?
a morphological defect of an organ, results from intrinsically abnormal developmental process
what is syndromic cleft lip/palate?
associated with more than 300 malformations
what is nonsyndromic cleft lip/palate?
CLAP, diagnosis by exclusion
what are some traits of cardiac defects?
5-8 per 1000 births, 2-3 of those are symptomatic in first year, major cause of death in first year
what is ventricular septal defects?
most common anomaly of cardiac defects, coarctation of aorta
what is spina bifida occulta associated with?
occulta= closed
what is lipomeningocele associated with?
lipoma or fatty tumor located over the spine
what is meningocele associated with?
fluid filled sac but neural tissue unaffected
what is myelomeningocele associated with?
spina bifida
what are some lifelong disabilities associated with spina bifida?
paralysis, loss of bowel and bladder control, learning disabilities
what is folic acid’s importance?
used to prevent anemia, neural tube defects, CAD, stroke and cancer
what is significant about S-adenosyl methionine?
aka SAM most important carrier of methyl groups
what are the major roles of folic acid aka vitamin b9?
involved in the biosynthesis of thymidylate and the purine nucleic acid bases and involved in the methylation of homocysteine to produce methionine
what is disruption?
morphological defect of an organ, results from extrinsic breakdown of the normal developmental process (trauma or teratogen)
what is cataract caused by?
congenital rubella infection
what are limb defects caused by?
due to talidomide exposure
what is a teratogen?
a drug able to produce defects in the developing fetus
what is amelia
complete absence of limbs
what is phocomelia
absense of middle portion of the limb
what is hypoplasia
the absence of some bones
what does the immunomodulatory properties of thalidomide therapeutic properties treat?
leprosy
what does non immunomodulatory properties of thalidomide therapeutic properties treat
cancer
what is deformation
morphological defect of an organ, results from abnormal mechanical force
what is club foot
most common disorder of the lower extremity, one of both feet turn downward or inward
what is dysplasia
morphological defect of a tissue, results from abnormal organization of cells into tissue, often caused by single gene defects
what is achondroplasia
accounts for 70% of diagnosed cases of dwarfism, abnormal body proportions, hump on back, large head and flat nose, shortened stubby fingers, trident hand
what is sequence
cascade of defects, arise from single prior anomaly or mechanical complex, usually sporadic with low recurrence risk
what is a syndrome
pattern of defects (not causing each other but altogether caused by same cause), pattern of abnormalities is consistent and recognizable
what is waardenburg syndrome?
piebaldism, deafness, and patching skin coloring. Caused by RET gene mutation
what is the KIT gene mutation responsible for?
piebaldism
what is association?
multiple abnormalities associated with each other, NOT sequence and NOT syndrome
what does VATER stand for?
V-vertebrate problems A-anal abnormalities T-trachea problems E-esophagus problems, R-radius problems
what is vater association?
malformations that tend to occur together more than might be expected due to chance
what is teratogenesis
environmental factors which can adversely affect the developing embryo
what is homeosis?
transformation of one body segment to another
what are HOX genes?
occur on the chromosome in the linear sequence corresponding to the part of the body axis controlled
what is IDX1/
a homeobox gene, required for pancreatic development
what is PAX6 mutation?
aniridia, complete loss of the iris
what is thanatophoric dysplasia?
mutation that increases receptor signaling by 100 fold
what is holoprosencephaly?
failure of the embryo’s forebrain to divide to form bilateral cerebral hemispheres causing
what is brachydactyly?
short fingers caused by IHH mutation
what are chromosomes
units where dna is packaged into
what does cytogenetics study
studies normal and abnormal chromosomes and their relationship to human development and disease
what is karyotype
test to identify and evaluate the size, shape, and number of chromosomes in a sample of body cells
what is sky (spectral karyotyping)
a molecular technique used to simultaneously visualize all the pairs of chromosomes in an organism in 24 different colors.
what is crossing over
an exchange of genetic material between homologous chromosomes,results in genetic recombination, Occurs during prophase I of meiosis (pachytene)
in a process called synapsis
what is paternal uniparental disomy
chromosomal doubling in spermatozoid after fertilization,
Egg genome is eliminate for some reason
what is maternal uniparental disomy
activation of unovulated oocyte
what is aneuploidy
loss or gain of chromosomes
what is polyploidy
extra set of chromosomes
what is mosaicism
two cell lines within the same body: e.g. one normal, one with mutation or chromosomal abnormality
what is chimaerism
two embryos mixed all together – e.g. male and female
what is trisomy 13
(patau syndrome),multiple malformations, severe developmental delay, no speech development
what is trisomy 19
edwards syndrome, severe talipes, horseshoe kidneys, severe retardation
what is gynecomastia
small testes,
inability to produce sperm;
Could have breast cancer, male with female features
what is triple x syndrome
Increased space between the eyes;
Epicanthal folds;
Could be mild intellectual impairment; could be not.
Sometimes neuromotor development is delayed….
Common problems with spontaneous abortion. Fertile, tall, looks normal
what is a paracentric chromosomal abnormality?
doesnt include centromere, inversion or loss of the fragment
what is pericentric chromosomal abnormality
includes centromere, inversion that includes centromere or loss of both telomeres with curling into the circle
what is a balanced chromosomal abnormality
no net gain or loss of chromosomal material
Translocations and inversions. No phenotype produced except cases when:
– Chromosomal break disrupts important gene
– Break separate gene from regulatory element
what is an unbalanced chromosomal abnormality
net gains or losses
Deletions and insertions
Unfortunately many translocations are accompanied by 100 kb – 1 Mb deletions
what is robertsonian translocation
Only happens
with chromosomes
13, 14, 15, 21 and 22
(rDNA carriers)
Both centromeres are present,
but they function as one,
so chromosome is stable
what is 4p syndrome
Severe growth retardation Psychomotor delay and mental retardation Dysgenesis of the corpus callosum Seizures Renal hypoplasia Ventricular septal defect -wolf-hirschorn syndrome Facial features
cri du chat syndrome
aka 5p deletion, Low birth weight, may have respiratory problems, Microcephaly, Mental retardation, Facial features Normal life expectancy In 80% of cases deletion is paternal
what is williams beuren syndrome
aka 7q11.2 syndrome, mild mental retardation (some are normal);
Strengths in auditory memory and language, extreme weakness in 3D skills (writing, math);
Elastin artheriopahty (elastin gene is deleted), arteries is narrow;
distinctive facial features
Hypercalcemia
Overfriendliness, generalized anxiety, and attention deficit disorder
what is jacobsen syndrome
aka 11q syndrome, mild to moderate psychomotor retardation, trigonocephaly, facial dysmorphism, cardiac defects, Thrombocytopenia
what is smith magenis syndrome
an inversion of the circadian rhythm of melatonin : sleep disturbances
(sleep whole day, party all night)
self-injurious behavior: head banging; hand/nail biting; skin picking; pulling off fingernails and/or toenails “for fun and when bored”. Other behavioural disturbances.
what is 22q11 deletion syndrome
a history of recurrent infection due to thymus agenesis or hypoplasia;
parathyroid gland hypoplasia (hypocalcemia)
heart defects
facial features.
what are chromosome instability syndromes
Caused by Mutations that leads to increase in the rate of chromosome breakage
Chromosomal rearrangements are consequences, not a cause here
Often lead to increased chance of cancer
what is raynauds sign
The fingers and/or toes
become white and/or blue ;
what is CREST syndrome
Calcinosis (calcium deposits), usually in the fingers;
Raynaud’s spasm of blood vessels in response to cold or stress.
Esophagus muscle control loss (difficulty swallowing)
Sclerodactyly, a tapering deformity of the bones of the fingers;
Telangiectasia, small red spots on the skin
what is nijmegen syndrome
congenital microcephaly, mild dysmorphic facial appearance, growth retardation, immunodeficiency, high risk for lymphoid malignancy
what is HNPCC
hereditary nonpoliosis colon cancer, inherited defect in mismatch repair enzyme, so patients accumulate a very high rte of genetic mutations
what is the key word to understanding of cancer phenomenon
progression
what are oncogenes
function to promote cell growth or inhibit cell death
what do tumor suppressor genes do
function to inhibit the oncogenic process, frequently act in recessive fashion
what is embolous formation
Cancer cells travel through the circulatory system
until it grows into a small plug.
Only 0.01% of cancer cells survive in circulation