Path Week 4: Path Development And Genetic Disease

Front 1

Birth Defect

Back 1

Congenital (present at birth) abnormality or disorder, may be due to abnormal genetic code or an acquired injury before birth.

Front 2

What types of diseases are neurofibromatosis and cystic fibrosis?

Back 2

Single gene (monogenic) defects.

Front 3

What are polygenic disorders, what are their recurrence risks

Back 3

Is a disorder caused by the combined effects of multiple genes and the environment. Recurrence risk is lower than a disease that is purely genetic.

Front 4

Preimplantation stage

Back 4

First 2 weeks after fertilization. Considered the all or none period; fetus will be healthy or will not take.

Front 5

Implantation and organogenisis stage

Back 5

Weeks 3-9. Where fetus is most susceptible to teratogens. Malformations result from abnormal development.

Front 6

Second and third trimester

Back 6

Not very susceptible to major malformations or teratogens because organs have already formed. However can get damage to already formed organs; usually in the form of deformations or disruptions.

Front 7

Agenesis

Back 7

Complete absence of an organ or its primordium.

Front 8

Aplasia

Back 8

Absence of organ but persistence of of the primordia or rudementary organ. (ex aplasia of globes)

Front 9

Hypoplasia

Back 9

Reduced size of an organ due to incomplete development.

Front 10

Atresia

Back 10

Failure of a lumen to form in organs which should have lumens.

Front 11

Dysplasia

Back 11

Abnormal cellular organization and the morphological results that follow. (ex renal dysplasia)

Front 12

Ectopia

Back 12

Organ outside the normal location or cells outside their normal origin.

Front 13

Malformation

Back 13

Structural defect present at birth due to abnormal development. Can be intrinsic (genetically determined) or extrinsic (teratogen).

Front 14

Deformation

Back 14

Abnormal form, shape, or position of a body part due to mechanical forces. Arises later in fetal life. Uterine constraints are most common. Recurrence risk is lower than a malformation.

Front 15

Disruption

Back 15

Destruction of an originally normal body region or organ caused by extrinsic force (ex. amniotic band sequence). No risk of recurrence.

Front 16

What are clues to ID amniotic band sequence

Back 16

Will see shreds of amnion on fetus. Will also usually be asymmetric.

Front 17

Sequence

Back 17

Multiple congenital abnormalities that are all secondary effects of a single problem. (ex. potter's sequence)

Front 18

Potter's sequence

Back 18

When a fetuses kidneys dont develop leading to a lack of urine production and therefore a lack of amniotic fluid (oligohydramnios). This lack of amniotic fluid leads to lung hypoplasia, squished faces known as potter's faces, and clubbed feet.

Front 19

Oligohydramnios, what is it and what is are the clinical results

Back 19

Not enough amniotic fluid. Nodules on the placenta (amnion nodosum) are a key finding.
Can result in lung hypoplasia, altereed faces, limb positioning defects.

Front 20

Syndrome

Back 20

Set of congenital abnormalities with a single cause (FAS, CMV infection, and all trisomys including down syndrome)

Front 21

Most common teratogen and most common form of preventable mental retardation

Back 21

Alcohol

Front 22

Pathology of Down syndrome

Back 22

-Flat faces
-Broad nasal bridges
-Slanted eyes with epicanthal folds
-Brushfield spots on the iris
-Transverse palmar creases
-Mental retardation
-Congenical heart malformations (ASD, VSD, endocardial cushion defects like AV canal)
-Have a 10-20x increased risk for acute leukemia
-All patients who survive to 40 will have Alzheimers.

Front 23

AV Canal

Back 23

Absence of inferior aspect of atrial septum and superior aspect of ventricular septum leading to a connection between atria and ventricles.

Front 24

Which maternal infections can be teratogens?

Back 24

TORCH;
T - Toxoplasma
O - Other (syphilis)
R - Rubella
C - CMV
H - Herpes

Front 25

Teratogenic effect of Rubella

Back 25

Risk of transmission is greatest during the first 8 weeks of pregnancy. Can cause abortion or Congenital Rubella Syndrome (CRS):
Petechia, Hepatosplenomegaly, cataracs, chorioretinitis, hearing loss, microencephaly, and congenital heart malformations (Patent Ductus areteriosus, VSD, ASD, tetralogy of fallot). Can possibly lead to diabetes.

Front 26

Tetralogy of Fallot

Back 26

Congenitcal heart malformation found in babies with congenital rubella syndrome. Has 3 parts:
1) Ventricular septal defect
2) Aorta dextroposed over the defect
3) Narrowing of pulmonary outflow tract.
All these lead to the secondary lesion, Right ventricular hypertrophy.

Front 27

Congenital CMV infection

Back 27

Most common fetal viral infection. 95% of cases are asymptomatic. Highest risk is second trimester.
Microencephaly, cerebral periventricular calcification, chorioretinitis, middle ear deafness, anemia.

Front 28

Congenital Syphilis Infection

Back 28

Doesnt invade fetus until 5th week:
Large placenta, hepatosplenomegaly, jaundice, anemia, thrombocytopenia, rhinitis (sniffles), rash with blisters on soles of hands and feet, glaucoma, meningitis. If not treated get tardive syphilis resulting in Hutchinson's triad, clutton's joints, saddle nose (no bridge), saber shin (anterior bowing) and mental retardation.

Front 29

Hutchinson's triad

Back 29

3 Symptoms of tardive syphilis:
1) Hutchinson's teeth (notched incisors)
2) Interstitial keratitis (inflamed cornea)
3) Deafness

Front 30

Fetal alcohol syndrome

Back 30

Most common teratogen and cause of preventable mental retardation:
-Mental retardation
-Growth retardation
-Microencephaly
-Cardiac septal defects
-Short palpebral fissures, flat philtrum, thin upper lip, maxillary hypoplasia

Front 31

Anticonvulsants as a teratogen

Back 31

Cause growth deficiency, mental retardation, hypertelorism, distal phalangeal hypoplasia and nail hypoplasia.

Front 32

Cocaine as a teratogen

Back 32

-Prematureity
-Low birth weight
-Microencephaly
-Retardation
-Abortions
-SIDS
-Intracerebral bleeding

Front 33

Cigarettes as a teratogen

Back 33

-Increased risk of abortion
-PreMe
-Low birth weights
-SIDS

Front 34

Retanoic Acid as a teratogen

Back 34

CNS, cardiac, and craniofacial defects including microtia/anotia (small/no ears), conotruncal cardiac defects, and spontaneous abortion.

Front 35

Metals as a teratogen

Back 35

Lead, cadmium, and Mercury poisoning.
Mercury inhibits migration of neuronal cells and effects brain. Get Cerebral palsy.

Front 36

Thalidomide as a teratogen

Back 36

Used as a sleeping pill in Europe, causes shortening/loss of limbs in fetus.

Front 37

Ionizing Radiation

Back 37

Mental retardation, microencephaly, blindness, skull defects, spinabifida.
Exposed infants have higher rates of leukemia and brain tumors.

Front 38

Maternal conditions which can act as teratogens.

Back 38

Diabetes
PKU - If diet not maintained, can lead to mental retardation, microencephaly, congenital heart disease, growth retardation and abortion.

Front 39

Osteogenesis imperfecta

Back 39

Auto dominant disorder which causes abnormal type 1 collagen. Cause:
-Bone fractures
-Short stature
-Deafness
-Blue sclera
-Type 2 babies die in utero

Front 40

Neurofibromatosis Type 1

Back 40

Most common AD train. Caused by mutation of 17q gene which encodes for neurofibromin which negatively regulates p21 ras oncoprotein:
Pathology keys are plexiform neurofibromas, lisch nodules, and six or more cafe au lait spots.
Tumors occur more often in these patients as well as skeletal lesions and neurofibrosarcomas.

Front 41

Turner syndrome

Back 41

45, X, most are lost early in pregnancy. Can present with:
-Hydrops fetalis (due to lympthatic issues)
-Posterior cystic hygroma
-Aorrtic coarction
-Horseshoe kidney