Definition: genetic makeup/the set of instructions that may or may not be expressed (observed) in the patient.
Definition: the physical appearance of an individual/the genetic instructions that have been expressed.
Phenotype (may be effected by environment)
Definition: trait that will be expressed in phenotype.
Definition: trait that might be expressed in phenotype.
Definition: the full chromosome set in a nucleus, often is the picture of the chromosomes.
Karyotype (represents the count)
Definition: having only one member of each pair of chromosomes (23).
Definition: having a "normal" number of chromosomes.
Definition: not normal number; loss or gain of chromosomes.
Definition: chromosome number that is a multiple greater than two of the haploid number.
Definition: the loss of a chromosome; autosomal NOT compatible with life.
Monosomy (45XO compatible, 45YO not compatible)
Definition: gain of a chromosome.
Trisomy (trisomy of sex chromosomes are compatible with life; trisomy 21 (Downs) and 18 (Edwards) are most common)
What is the normal human chromosomal nomenclature for males and females?
What nomenclature is an example of an extra autosomal chromosome?
What are examples of chromosomal nomenclature that show a variation in sex chromosomes?
47XXY (extra sex chromosome)
45XO (absent sex chromosome)
What is an example of chromosomal nomenclature for missing part of a chromosome?
46XY del (5p) or 46XY (5p-)
"Cri du Chat syndrome"
What is the overall incidence of Down's Syndrome (Trisomy 21) and how does maternal age affect it?
1 in 700-800 live births
<20 years old (mother), 1:1550
>45 years old (mother), 1:25
What is the pathogenesis of Down's Syndrome?
Mostly maternal origin and is a consequence of "nondisjunction" during meiotic division.
What are the characteristics manifested in someone with Down's syndrome?
Epicanthal folds (eyes)
Large protruding tongue
Low set ears
"Simian" crease in palm
Congenital heart defects
Often sub-100 IQ
Alzheimer's very early (30-35?)
What is the incidence rate of Klinefelter's Syndrome (47XXY, male phenotype)?
1 in 700 males; increases with age of mother.
What is the pathogenesis of Klinefelter's Syndrome?
Abnormal segregation of X or Y chromosomes in the gonads (non-disjunction), not usually inherited since patients are typically infertile (testes atrophic and unable to produce sperm).
What are the clinical characteristics of Klinefelter's Syndrome (47XXY, male phenotype)?
Small penis, small firm testes
Diminished pubic, axillary, and facial hair
Gynecomastia (enlarged breasts)
Abnormal body proportions (long legs, short trunk)
What is the incidence rate of Turner's Syndrome (45XO, female phenotype)?
1 in 3000 females
What is the pathogenesis of Turner's syndrome?
Abnormal segregation of X or Y chromosomes during meiosis in the gonads (spontaneous mutation, usually with older mothers, not inherited).
Normal female organs except ovaries which don't develop normally (usually infertile).
Do NOT naturally develop secondary sex characteristics, hormones can correct appearance but not infertility.
What are the clinical characteristics of Turner's syndrome (45XO, female phenotype)?
"Shield-shaped", broad, flat chest
Coarctation of the aorta
Absent or delayed development of secondary sex characteristics ("streak" ovaries, amenorrhea, infertility)
What are the three patterns of inheritance for single gene disorders?
Autosomal dominant: in heterozygous pair, the one that is expressed (Aa)
Autosomal recessive: in a heterozygous pair (Aa)-recessive gene not expressed, dominant gene is expressed, must have homozygous pair (both recessive) to be expressed (aa).
X-linked disorders: males can ONLY be hemizygous (XY), women are homozygous or heterozygous (XX or XX).
What are some examples of autosomal dominant disorders?
Familial hypercholesterolemia (1 in 500)
Marfan's syndrome (1 in 10,000)
Polycystic kidney disease
Von Willebrand's clotting disorder
**disorders may also develop from new mutations (egg/sperm) which presents no risk of unaffected siblings from transmitting the trait**
What is the cause and sign of familial hypercholesterolemia?
Mutation in gene encoding low density lipoprotein cholesterol (LDL-C); less LDL is removed from blood by liver cells.
Deposition of lipids in tissues can lead to xantholasma (deposits in skin).
What condition causes connective tissue dysfunction in fibrillin which affects tendons and connective tissue of vessels?
What is the most commonly inherited kidney disease? When does it present?
Polycystic kidney disease
Present at age 20-40
What are the signs and symptoms of polycystic kidney disease?
Abdominal/flank pain (due to large kidneys)
Hypertension in 50-80%
PMH of UTI and nephrolithiasis
Large kidneys on physical exam
Other findings include hepatic cysts, cerebral aneurysm (50% will eventually need kidney transplant).
What is Huntington's chorea and when do symptoms start?
Premature brain cell death causing atrophy in cerebral cortex and caudate.
Symptoms start at age 30s or 40s
What are the signs and symptoms of onset of Huntington's chorea?
Involuntary movements (chorea)-cannot maintain tongue in protruded position
Changes in behavior and personality (irritability)
Cognitive impairment (dementia)
What is the life expectancy of a pt diagnosed with Huntington's chorea? What are the causes of death?
10-15 yrs after diagnosis
Pneumonia, falls, suicide
What condition is a result of a defect in the production of Type I collagen which can lead to easy fractures, loose joints, scoliosis, blue sclerae and hearing loss?
Osteogenesis imperfecta (can also be due to a spontaneous mutation)
What kind of disorders make up the largest group of Mendelian (genetic) disorders, in which phenotype is seen in the homozygous state where BOTH recessive genes are present? Which children tend to get these?
Autosomal recessive disorders
Children from parent who are BOTH asymptomatic carriers (heterozygotes)-onset of symptoms are usually early in life
What are some examples of autosomal recessive disorders?
Cystic fibrosis (most common)
Sickle cell anemia
Wilson's Disease (Kayser-Fleishcer ring=copper)
What is the incidence rate of cystic fibrosis for the general public and for those born to parents who are carriers?
General: 1:2500 live births
Carriers: 1:25 live births
**it is the most common lethal autosomal recessive disorder, and occurs mostly in Caucasians**
What is the pathogenesis of cystic fibrosis?
Defect in transport of chloride across cell membrane (excess NaCl in sweat), and abnormally thick mucous secretions that block the airways and pancreatic ducts.
What are the clinical characteristics of cystic fibrosis?
Pulmonary infections and pancreatic insufficiency (85%)
Diagnosed by sweat chloride test in newborns
What is the incidence rate for sickle cell disease? What part of the population gets this condition?
1 in 500 Black/African American births
**1 in 12 have Sickle cell trait (only one gene)**
What is the pathogenesis of sickle cell disease?
Defect in synth of β chain of Hgb which causes sickling of Hgb at low O2 tension.