Part 1

Question 0

Connatal malformation

Answer 0

Deformation: pes equinovarus
Disruption: torticollis (wry neck, ngheo co)
Deformation sequence: arthgryposis multiplex congenita (AMC) characteristic by multiple joint contracture, muscle weakness and fibrosis
Disruption sequence: ADAM syndrome

Question 1

Minor abnormalies

Answer 1

simian crease, preauricular tag/fistula, supernumerary nipples

Question 2

Definition of congenital malformation

Answer 2

Physical defect present in a baby at birth (genetic or prenatal event)
Development of a structure is arrested and misdirected, delayed and the effect is permanent

Question 3

Social significance of congenital malformation

Answer 3

Leading cause of infant mortality in US and many developed contries
1/3 babies in US

Question 4

Reduced penetrance

Answer 4

Abnormal gene is present but it does not manifest it self in the phenotype
Some people with the mutation but do not develop disorder’s feature

Question 5

Variable of expressivity

Answer 5

Range of signs and symptoms that occur in different people with the same genetic condition
Exp: marfan syndrome

Question 6

Apert syndrome

Answer 6

Dominant disorder
Chromosome 10
FGFR2 mutation
Features:
Clover shape head
Mild/moderate/severe mental retardation
Limb disturbance (syndactyly)
Congenital heart defect

Question 7

Achondroplasia

Answer 7

Dominant mutation
Chromosome 4p 1138 Arg-Gly
FGFR3 mutation 
Features:
Bone, connective tissue, muscle are involved
Low muscle tone (hypotonity)
Slow motor movement
Abnormal skull structure

Question 8

Codominance

Answer 8

A phenomenone in which a single gene has more than one dominant allele
Express the phenotype associated with both alleles
Exp: blood group

Question 9

Marfan syndrome

Answer 9

Autosomal dominant, variable expressity
Chromosome 15 (15q15-q21.3)
Fibrillin-1 mutation (component of elastin)-> weaker elastin
Incidence: 1/10000
Features:
Pectus exavatum, carinatum
Scoliosis
Ectopia lentis
Dilatation of the aorta, aortic dissection

Question 10

Mitochondrial gene

Answer 10

Single chain, circular, called mDNA, 37 genes, code for ATP producing metabolic pathway
High mutation rate but no repair mechanism
Variable expressity
Maternal inheritance

Question 11

Mitochondrial inheritance diseases

Answer 11

Hereditary opticus neuropathy
MERF (myoclonic epilepsy-Ragged red fiber)
Kaerms Sayre syndrome
MELAS (mitochondrial enceloparhy lactase acidosis stroke like episode)

Question 12

Hereditary opticus neuropathy

Answer 12

Leber disease
Point mutation: 11778 position of ND4 gene
Maternal inheritance
Visual loss, neurological symptoms

Question 13

MERF (myoclonic epilepsy Ragged red fiber)

Answer 13

Point mutation in Lys gene of tRNA
Sporadic/maternal inherit
Myo epilepsy, neurological symptoms, ataxia, dementia, myopathy due to Ragged red fiber in muscle

Question 14

Kaerms-Sayre syndrome

Answer 14

Mitochondrial inheritance disease
Big tandem mutation, big deletion
Sporadic inherit
AV block, cerebellar damage, retinopathy, external opthalmogia, deafness, hypotone

Question 15

MELAS (mitochondrial encelopathy lactate acidosis stroke like episode)

Answer 15

Mitochondrial inheritance disease
Point mutation in Leu gene of tRNA
Sporadic/maternal
Severe hypotone
Nygstamus
Encelopathy
Behavioral diaturbance

Question 16

Fragile X syndrome

Answer 16

Triple expansion CGG triplet in the 5’ non translated region of FMR 1 gene (fragile mental retard)
Chromosome X q27.3
1:1000-4000 male
1:2000-6000 female (1/259 fm carrier)
29-50 healthy
52-200 unstable
>200 gene methylation-> loss of gene function (folic acid)
No neuron maturation
Features: mental retardation, autism, delay of speaking, big head long face, hyperactive

Question 17

Triplet expansion related disease

Answer 17

Fragile X syndrome CGG Xq27.3 FMR1
FRAX E CGG Xq28
FRA-F
Hungtinton Chorea: CAG, 4p16.3
Spinobulbar muscular atrophy

Question 18

Down syndrome

Answer 18

Trisomy 
Critical segment 21q22
Critical region 21q22.1
Features
Short neck, small ear, straight hair, upward slanting of eyes, small mouth of large tongue, flat face
Various degree of mental retardation
Congenital heart disease
Risk of leukemia 
Early onset of Alzheimer, dementia

Question 19

Cytogenetics of Down syndrome

Answer 19

47, XX/XY +21 (95%)
46, XY, rob(21,22) +21
45 XX, -21,-22 t(21,22)
46, XY, -13,-14, t(13,14), +21

Question 20

Down syndrome related genes

Answer 20

Gout gene: purine synthesis, mental retardard
CRYA1 gene: crystalline-> disturbance of lens
APP and AD1 gene: Alzheimer’s gene

Question 21

Hemophilia

Answer 21

X linked recessive disease
Spontaneous mutation
Xq 26-28
A factor VIII (33%), B factor IX 20%

Question 22

Dunchenne muscular dystrophy

Answer 22

X link recessive disease
Dystrophin gene Xq21.2 delete mutation
Dystrophyn is intracellular protein in 2 transmembrane complex (dystroglycan- sacroglycan)
Variable expressity
Features:
Muscle weakness
Walking on tip toe, difficult climbing the stare
Standing up from crouching
Gover’s symptoms: patients have to use their arm to walk up due to weakness of hip and thigh muscle
Cardiomyopathy