S3M1 Pathology Yakubovskyy Genetic Disorders

Front 1

What disease is this:
-Flat face
-oblique (upslanting) eyes
-epicantic folds
-large tongue
-deep palmar crease
-extra skin on neck

Back 1

Down syndrome

Front 2

What are some major complications postnatally with Down syndrome?

Back 2

Congenital heart disease (mainly septal defects)
Acute leukemias
Alzheimer disease
Males are sterile, females can reproduce

Front 3

What is the first semester tests for Downs?

Back 3

Nuchal translucency (should be 3-4)
-Beta-hCG
-PAPP-A

(High, High, Low)= DS

Front 4

Clinical hallmark of this disease is primary amenorrhea and sterility.

Back 4

Turner syndrome

Also:
Short stature
Webbed neck
Coarctation of the aorta

Front 5

What is the gene involved in klinefelter syndrome?

Back 5

The androgen receptor (AR) gene on Xq11-12

Contains lots of CAG repeats; the longer the repeats the lower the response to androgens

Front 6

Disease with testicular atrophy and hyalinization of seminiferous tubules with Leydig cell hyperplasia due to increased LH and FSH.

Back 6

Klinefelter syndrome

There is also high estradiol and low testosterone

Front 7

This disease is a 22q11 deletion with facial malformations, cleft palate, cardiac malformations and hypocalcemia due to parathyroid hypoplasia?

Back 7

Velocardiofacial syndrome or DiGeorge syndrome (CATCH-22)

Front 8

What is the most common mendelian disorder?

Back 8

Familial hypercholesterolemia
Mutation of LDL receptor gene on chromosome 9p13

Causes accelerated atherosclerosis

Front 9

With high cholesterol, you can see ischemic heart disease, xanthomas and _____?

Back 9

Xanthelasmas: Cholesterol-containing yellow plaques in eyelids

Front 10

Marfan is an AD disorder affecting the skeletal and cardiovascular systems. It is caused by a missense mutation in what gene?

Back 10

FBN1 gene on chr 15q21

Front 11

What protein is abnormal in Marfan syndrome?

Back 11

Abnormal fibrillin 1 and irregular scaffolding for tropoelastin.

Front 12

What chest deformaties are consistant with Marfans?

Back 12

Pectus excavatum, pectus carinatum or scoliosis.

Front 13

Histologically, what 2 things indicate Marfans syndrome?

Back 13

1.) Loss of elastin
2.) accumulation of GAGs

Front 14

Describe Ehler Danlos syndrome.

Back 14

Collagen defect presenting with hyperelasticity and fragility of skin, Joint hypermobility and bleeding diathesis (large artery rupture).

Front 15

These diseases usually have complete penetrance, less variable expressability, Early onset and new mutations are difficult to identify.

Back 15

Autosomal recessive disorders

Usually enzyme deficiency

Front 16

Gaucher disease is a common Ar disorder with a single base mutation in the...

Back 16

B-glucocerebrosidase gene on chr. 1q

Front 17

Gaucher disease is an accumulation of glucocerebrosides within what organs?

Back 17

liver, spleen, lymph nodes and bone marrow.

Usually results in hepatosplenomegaly in type 1

Front 18

This is a disease where you have an accumulation of glucocerebrosides within the cytoplasm of mononuclear phagocytes; cells take on a wrinkle tissue paper appearance.

Back 18

Gaucher disease

Front 19

Type ______ gaucher disease is the most common lysosomal storage disease.

what is the clinical presentation?

Back 19

Type 1

Adult ashkenazi jews
variable expressability
hepatosplenomegaly

Front 20

How do you treat Gaucher disease?

Back 20

IV administration of modified glucocerebrosidase

Front 21

Tay-sachs disease is a frameshift mutation in what gene?

Back 21

hexaminidase A on chr 15

Front 22

Tay-Sachs disease is a very severe lysosomal disease characterized by accumulation of _________ within the nervous system. This is caused by a frameshift mutation in ____________ gene.

Back 22

gangliosides

hexaminidase A

Front 23

Tay-Sachs disease:
1.)distended neurons with vacuoles containing lipids
2.) concentric whorls of lamellar structures.
3.?

Back 23

Chery-red macula

Also by 6-10 months: progressive motor and mental retardation, seizures

Front 24

Mucopolysaccharidoses is the old term for....

Back 24

GAG's

Front 25

What is the most common lysosomal storage disease with accumulation of GAGs in the liver, spleen, heart and blood vessels?

Back 25

Hurler disease

Front 26

What are common clinical features of hurler disease?

Back 26

Coarse facial feature, skeletal abnormalities (gargoylism) and joint stiffness.

Front 27

Hurlers disease is caused by a mutation in _____________ gene.

Back 27

Alpha-L-iduronidase

Front 28

Describe the pathogenesis of hurlers disease.
1.)mutation in alpha l iduronidase
2.) Gag accumulation within the interstitium and heart
3.)
4.)

Back 28

3.) Tissue swelling/enlargement with lumina/orifice obstruction
4.) Death within 6-10 yrs

Front 29

Hurler disease problems:
1.)Corneal Opacification
2.)Bone changes
3.)
4.)

Back 29

3.) Endocardial swelling
4.) Facial Dismorphism

Front 30

Von Gierks disease is a ___________ deficiency?

Back 30

Glucose 6 Phosphatase deficiency.

Causes growth retardation

Front 31

McArdle disease is a ________________ deficiency.

Back 31

Muscle phosphorylase def

causes muscle cramps

Front 32

Pompe disease is a deficiency is......

Back 32

Acid maltase (alpha-glucosidase

Causes lysosomal accumulation of glycogen and cardiomegaly

Front 33

Fragile X is a CGG repeat expansion @

Back 33

CGG repeat @ X q-arm in the FMR1 gene
50-200 premutation
>200=disease

Front 34

Describe the mechanism of the defect in Fragile X.

Back 34

There is hypermethylation (silencing) of the FMR protein expressed in the brain and testicles.

The FMR function is to inhibit synthesis of proteins that regulate function of dendritic synapses

Front 35

What are the deficiencies in Fragile X?

Back 35

2nd most common inherited form of mental retardation
-impaired language,
-macroorchidism

Front 36

On normal paternal chromosome 15, _____ gene is expressed and ________ is silenced.

Back 36

Prader-Willi

Angelman

Front 37

Absence of PW gene on paternal chromosome=

Back 37

Prader willi syndrome

Front 38

What is the genetic mechanism behind Prader willi and angelman?

Back 38

Chromosome deletion
Uniparental disomy(both homologous chromosomes are inherited from one parent)

Front 39

In Angelman syndrome, the loss of the angelman gene on the maternal chr. 15 leads to a def. in what protein?

Back 39

Deficiency in ubiquitin-mediated protein degradation in the brain