Genetic Diseases

Front 1

Huntington disease (Huntington's Chorea):
Inheritance pattern?
Gene affected?
Clinical features?
Life expectancy?

Back 1

Inheritance pattern: Autosomal dominant
Gene affected: Triplet repeat expansion Coding region of HD, The CAG repeat gets too large and becomes unstable
Normal_Less than 36
Intermediate_36-39 (usually affected)
Affected_Greater than 40

Clinical features: Mean age of presentation 35-44years with an average survival of 15-18years after diagnosis. Progressive motor, cognitive, & psychiatric abnormalities that become incapacitating as HD progresses, Chorea (nonrepetitive jerks that can't be voluntarily controlled)

Life expectancy: Mean age of death is 55

Front 2

Achondroplasia:
Inheritance pattern?
Clinical features?
Gene affected?
Life expectancy?

Back 2

Inheritance pattern: Autosomal dominant, 100% penetrance, De novo mutations cause 75-80% of cases

Clinical features: Short stature, Proximal shortening of the limbs, Limits of elbow extension, Bow legs, Lumbar lordosis, Large head with frontal bossing, Normal intelligence

Gene affeted: Fibroblast growth factor receptor-3 (FGFR3).

Life expectancy: Usually normal

Front 3

Cystic fibrosis Inheritance pattern? Gene affected? Disease frequency?

Back 3

Inheritance pattern: Autosomal recessive Gene affected: CFTR (chlorine channel gene) (e.g. mutation - has a 3 base pair (in-frame) deletion). Chromosome 7.

Disease frequency: 1/2,000

Front 4

Sickle cell anemia:
Inheritance pattern?
Clinical features?
Gene affected?
Life expectancy?

Back 4

Inheritance pattern: Autosomal recessive, Heterozygous individuals have increased malaria resistance

Clinical features: Symptoms by 4 months of age, Blocked blood vessels cause acute painful crisis lasting hours to days. Repeated crises cause damage to kidneys, lungs, bones, eyes, & CNS

Gene affected: B-globin chain (Glu6Val)

Life expectancy: Shortened

Front 5

Duchenne muscular dystrophy (DMD):
Inheritance pattern?
Clinical features?
Gene affected?
Life expectancy?

Back 5

Inheritance pattern: X linked recessive, 1/3 of cases represent new mutations, 5-10% of carrier females have muscle weakness, while only a few have severe disease

Clinical features: Progressive muscle weakness & loss of muscle mass.

Gene affected: Dystrophin (< 5% normal levels)

Life expectancy: Symptoms by 5yrs, in wheelchair by 11yrs, death in teens or early 20s.

Front 6

Hemophilia A:
Inheritance pattern?
Frequency?
Clinical features?
Gene affected?
Treatment?
Life expectancy?

Back 6

Inheritance pattern: X linked recessive
Frequency: Males-1/10,0000

Clinical features: Coagulation disorder with prolonged bleeding & easy bruising

Gene affected: Coagulation Factor VIII

Treatment: Administering Factor VIII concentrate

Life expectancy: Approaches that of healthy population (excluding HIV or hepatitis)

Front 7

MELAS:
Inheritance Pattern?
Clinical Features?

Back 7

Inheritance Pattern: Mitochondrial

Clinical Features: Mitochondrial encephalopathy, lactic acidosis, and stroke like episodes

Front 8

MEERF:
Inheritance Pattern?
Clinical Features?
Genes Affected?

Back 8

Inheritance Pattern: Mitochondrial

Clinical Features: Myoclonic epilepsy seizures, optic atrophy, hearing impairment, demential, myopathy

Gene Affected Lysine tRNA

Front 9

Leber Hereditary Optic Neuropathy:

Inheritance Pattern?
Clinical Features?
Disease Onset?
Gene Affected?

Back 9

Inheritance Pattern: Mitochondrial

Clinical Features: Retinal degeneration, occasional cardiac conduction defects

Disease onset: 20-30yrs of age

Gene affected: Mutations in ND, ND4 and ND6

Front 10

Angelman syndrome:
Inheritance pattern?
Clinical features?
Gene affected?

Back 10

Inheritance pattern: Maternally inherited (paternal copy of the gene is imprinted [methylated] so it is not expressed).

Clinical features: Short stature, Always smiling, Severe mental retardation, Spasticity, Dystonia

Gene affected: Ubiquitin UBE3A gene on 15q11

Front 11

Prader-Willi syndrome:
Inheritance pattern?
Clinical features?
Gene affected?

Back 11

Inheritance pattern: Paternally inherited (maternal copy of the gene is imprinted [methylated] so it is not expressed).

Clinical features: Hyperphagia, Obesity, Hypogonadism, Small hands & feet, Mental retardation, Associated with cryptorchidism

Gene affected: SNRPN gene on 15q13

Front 12

Down syndrome:

Chromosomal abnormality?
Clinical features?
Frequency?

Back 12

Chromosomal abnormality: Trisomy 21, Usually due to non-disjunction during meiosis I in mother, Most common human malformation

Clinical features: Short stature, Brachycephaly (wide head) with flat occiput, Short neck, Loose skin on the nape, Flat nasal bridge, Ears low-set with characteristic folds, Mouth is open, protruding tongue, Epicanthic folds [skin fold of the upper eyelid (from the nose to the inner side of the eyebrow) covering the inner corner (medial canthus) of the eye] & Upslanting palpebral fissures, Hands are short & broad, Cardiac malformations, Mental retardation

Frequency: Most common human malformation syndrome

Front 13

Turner syndrome:

Chromosomal abnormality?
Clinical features?
Frequency?

Back 13

Chromosomal abnormality: Monosomy X, Less frequent in liveborn infants by far the most common chromosome anomaly in spontaneous abortions

Clinical features: Short female, Low posterior hair line, Webbed neck, Broad chest & widely spaced nipples, Pigmented nevi, Peripheral lymphedema at birth, Cubitus valgus [elbows are turned in], Coarctation of aorta

Frequency: 1/5,000 females

Front 14

Breast cancer: Inheritance pattern? Contributing genes?

Back 14

Inheritance pattern: Autosomal dominant with penetrance up to 85% for breast and 55% for ovarian cancer in females. Males also have an increased risk of breast, prostate, pancreatic, & other cancers. Contributing genes: BRCA1 & BRCA2 are the 2 genes identified so far. Both are involved in repair of DNA double-strand breaks.

Front 15

Familial Adenomatous Polyposis (FAP): Inheritance pattern? Gene affected? Clinical features? Diagnosis?

Back 15

Inheritance pattern: Autosomal dominant with very high penetrance Gene affected: APC (chromosome 5) tumor suppressor gene. There are many different mutations. Clinical features: Multiple (>100) benign adenomatous polyps, usually in the proximal colon with a high chance that one or more of the polyps will progress to a carcinoma Diagnosis: Colonoscopy to see polyps

Front 16

Attenuated Familial Adenomatous Polyposis (AFAP): Inheritance pattern? Gene affected? Clinical features?

Back 16

Inheritance pattern: Autosomal dominant with lower penetrance than FAP Gene affected: APC (chromosome 5) tumor suppressor gene. There are many different mutations. Clinical features: Variable number of polyps that are often found in the proximal colon, with a later age of onset

Front 17

Diabetes Mellitus Type I (T1DM): Genetics or Environment? Contributing genes? Biochemistry? Onset? Treatment?

Back 17

Genetics or Environment: Environment plays a large role because environmental changes trigger the disease Contributing genes: Has one major risk locus (IDDM1) & up to 20 minor loci that interact to confer susceptibility to environmental triggers Biochemistry: Complete loss of B-cell function due to autoimmune reaction Onset: Peak age in adolescence Treatment: Regular injections of insulin to control blood sugar

Front 18

Coronary artery disease: Contributing genes? Risk increase?

Back 18

Contributing genes: CDKN2A and CDKN2B genes on chromosome 9p21.3 play an important role in regulation of cell cycle and may be implicated through their role in growth inhibition, in the pathogenesis of atherosclerosis. Risk increase: 36% for each copy in a person's genome

Front 19

Hypophosphatemic rickets (vitamin D-resistant rickets): Inheritance pattern? Biochemistry?

Back 19

Inheritance pattern: X-linked dominant Biochemistry: The ability of the kidney tubules to reabsorb filtered phosphate is impaired

Front 20

PKU (phenylketonuria): Inheritance pattern? Disease frequency? Screening? Treatment?

Back 20

Inheritance pattern: Autosomal recessive Disease frequency: 1/1,000 Screening: Phenylalanine blood level test 3 days after birth. Treatment: Phenylalanine-restricted diet early in infancy to prevent mental retardation

Front 21

Tay Sachs: Inheritance pattern? Gene affected? Biochemistry? Clinical features? Disease frequency?

Back 21

Inheritance pattern: Autosomal recessive Gene affected: Hexoseaminidase gene has four base pair (frameshift) insertion, Chromosome 15 Biochemistry: Accumulation of gangliosides Clinical features: Child appear to develop normally for the first few months of life. Then, as nerve cells become distended with fatty material, a relentless deterioration of mental and physical abilities occurs. The child becomes blind, deaf, and unable to swallow. Muscles begin to atrophy and paralysis sets in. Other neurological symptoms include dementia, seizures, and an increased startle reflex to noise. Usually die by age 4, from recurring infection Disease frequency: Normal-1/360,000 Ashkenazi Jews-1/3,600

Front 22

Hemochromatosis: Gene affected? Carrier frequency? Clinical Features? Treatment? Life expectancy?

Back 22

Gene affected: Variety of mutations, but most common is an individual homozygous for a Cys282Tyr mutation in the HFE gene [Chr 6] Carrier frequency: USA-1/10 Clinical Features: Increased absorption & deposition of iron which can lead to liver, pancreatic, & cardiac damage. Skin may also become pigmented. Treatment: Phlebotomy, which is effective in preventing organ damage if instituted early Life expectancy: Normal

Front 23

Becker Muscular Dystrophy: Inheritance pattern? Clinical features? Gene affected?

Back 23

Inheritance pattern: X linked recessive, new mutations account for a small percentage of cases Clinical features: Progressive muscle weakness & loss of muscle mass. Not as severe as DMD. Gene affected: Dystrophin (30-80% normal levels)

Front 24

Patau syndrome: Chromosomal abnormality? Clinical features? Frequency?

Back 24

Chromosomal abnormality: Trisomy 13 Clinical features: Multiple anomalies (cardiac in 90% of cases) with very poor prognosis (few weeks) Frequency: 1/5000 births

Front 25

Edwards syndrome: Chromosomal abnormality? Clinical features? Frequency?

Back 25

Chromosomal abnormality: Trisomy 18 Clinical features: Multiple anomalies (cardiac in 90% of cases) with very poor prognosis (few weeks) Frequency: 1/5000 births

Front 26

Klinefelter syndrome: Chromosomal abnormality? Clinical features? Frequency?

Back 26

Chromosomal abnormality: 47,XXY Clinical features: Tall male, Infertile, Hypogonadism, Learning difficulties in some patients, May have poor psychosocial adjustment Frequency: 1/1000 males

Front 27

Retinoblastoma: Inheritance pattern? Gene affected?

Back 27

Inheritance pattern: Autosomal dominant, however gene affected is recessive (the other copy is almost always damaged in at least one cell during mitotic division) Gene affected: Rb gene (chromosome 13), which controls the progression of G1 to S phase

Front 28

Mytonic dystrophy:
Inheritance pattern?
Gene affected?
Clinical features?

Back 28

Inheritance pattern: Autosomal dominant

Gene affected: Triplet repeat expansion. 3' untranslated region of DMPK on chromosome 19, The CTG repeat gets too large and becomes unstable
Normal_Less than 30
Intermediate_50-80 (may be mildly affected)
Affected_80-2000

Clinical features: Muscles contract but have decreasing power to relax. With this condition, the muscles also become weak and waste away. Myotonic dystrophy can cause mental deficiency, hair loss and cataracts.

Front 29

Fragile X syndrome:
Inheritance pattern?
Gene affected?
Clinical features?

Back 29

Inheritance pattern: X-linked

Gene affected: Triplet repeat expansion. 5' untranslated region of FMR1, The CGG repeat gets too large and becomes unstable
Normal_Less than 60
Intermediate_60-200 (usually unaffected)
Affected_Greater than 200

Maternal Typically displays anticipation

Clinical Features: Males more severely affected. Mental retardation, Hyperactivity, Short attention span, Tactilely defensive (having a negative response to touch), Hand-flapping, Hand-biting, Poor eye contact, Perseverative speech (ontinued repetition of words or phrases), Hyperextensible MP joints (double jointed), Large or prominent ears, Large testicles, Simian crease or Sydney line (horizontal crease that goes from edge to edge across the palm)
Family history of mental retardation

Front 30

Familial hypercholesterolemia Inheritance pattern? Gene affected?

Back 30

Inheritance pattern: Autosomal dominant Gene affected: LDL receptor gene has a mis-sense mutation

Front 31

Warfarin (Dose variation): Genes involved?

Back 31

Genes involved: CYP2C9: Explains 10% of dose variations & is responsible for the break down of the drugs into metabolites VKORC1: Explains 25% of dose variations and is a gene for subunit C1 in the protein Vitamin K epoxide reductase, which is the target for the drug. Warfarin: (1) An oral anticoagulant used to prevent thrombosis and embolism in many situations (2) Has a narrow therapeutic index (3) Complex pharmacology (4) Errors in dosing can lead to severe & possible life-threatening bleeding or clotting (5) Its affect has to be monitored by frequent blood testing (6) It inhibits the action of Vitamin K epoxide reductase, which helps limit blood coagulation

Front 32

Hereditary non-polyposis colon cancer (HNPCC): Inheritance pattern? Gene affected? Clinical features? Onset?

Back 32

Inheritance pattern: Autosomal dominant Gene affected: MSH2 & MLH1 and some other MMR gene mutations responsible for about 60% most cases Clinical features: Has extremely variable expression. Individual has predisposition to colon [usually in distal colon] & extra-colonic cancers (endometrium, ovary, stomach, urogenital). Onset: Between 20-80 years.

Front 33

Glucose 6 Phosphate dehydrogenase (G6PD):
Inheritance Pattern?
Clinical Symptoms?

Back 33

Inheritance Pattern: X-Linked Recessive
Clinical Symptoms: Hemolytic anemia on ingestion of drugs such as primaquine, sulfa drugs, etc..

Front 34

Osteogenesis Imperfecta:

Inheritance pattern?
Clinical Symptoms?
Heterogeneity Type?

Back 34

Inheritance Type: Autosomal Dominant

Pleotropic Disease (multiple organ systems involved) bone and sclera
Defect in collagen formation.

Locus Heterogeneity: Chromosome 7 or Chromosome 17 mutation

Front 35

Marfan's Syndrome:

Inheritance Type?
Clinical Symptoms?

Back 35

Inheritance Type: Autosomal Dominant

Pleiotropic disease: mutation of fibrillin gene affects multiple organ systems. Skeletal abnormalities (long limbs, pectus excavatum), hypermobility of joints, ocular abnormalities (myopia, lens dislocation), cardiovascular problems (Mitral valve prolapse, aortic aneurysm)

Front 36

Acute intermittent porphyria:

Inheritance Type?

Back 36

Inheritance: autosomal dominant