Genetics - DR Abo-ElAsrar - by El Azhar Medical Students 2012

( BETA EDITION)
With
Prof. Dr Mohammed Abo El-Asrar
Edited By
El-Azhar Medical students 2012
Geneti cs Dr. Abo -Asrar

Genetics INDEX
Total pages = 39
Total time = about 6.5 hours
Lecture number
Pages
1- lecture 28 4 - 9
basics ( page 4 )
inheritance 6 ( Autosomal inheritance 6 )
2- lecture 29 10 - 16
cont. inheritance
( Sex chromosome inheritance 9 + Y - linked inheritance 12 + Co - dominant inheritance 12
+ Intermediated inheritance 13 + Germline mosaicism 13 + mitochondrial inheritance 13
+ Genetic hetero-genicity 14 + Multi factorial inheritance 14 )
Chromosomal aberration ( page 14 )
( Etiology 14 + Mechanisms 14 )
3- lecture 30 17 24
cont. mechanisms ( page 16 )
Classification of chromosomal aberration ( page 18 )
Down syndrome ( page 19 )
4- lecture 31 24 - 29
cont. down ( page 24 )
Trisomy 13 ( page 28 )
Trisomy 18 ( Edward syndrome ) ( page 29 )
anti mongolism = 21 Q ( page 30 )
cri-du-chat-syndrome = 5 P ( page 30 )
turner syndrome ( page 31 )
clinical features of Down on data show ( page 33 )
5- lecture 32 29 - 37
cont. turner ( page 35 )
Klinefelter syndrome ( page 37 )
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Geneti cs Prof. Dr. Abo El-Asrar

28
Genetics
: 1- Inheritance
2- Chromosomal abnormalities
Basics
basics
46 .. .. So, called 23 pairs of chromosomes
23 ) 22 pairs ( autosomal ) + 1 pair ( sex 22 pairs ( ) Called autosomal chromosomes
sex chromosome 1 pair
or XY May be XX
anatomy chromosome DNA mitosis .. meiosis metaphase chromatid by centromere centromere chromosome ) Short arm and long arm( short arm ( .. ) .. P long arm Q chromosomes .. 3
Long , Short & Medium size
chromosome .. X
chromosome ,,,
centromere
centromere .. short and long arm centromere:
1- Metacentric chromosome beside the center
long and long arm
) 2- Centromere in extremities Acro - centric chromosome ( acro means
short arm .... 21, 18, 22 ) called Sub metacentric chromosome ( 3- if between 1 & 2
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chromosome ( 2 chromatids ) when no cell division ,,,, ... ..

( ) ..
arm ( Electron microscope ) .. 9 ( arm )
region .. arm region .. 4 - 3- 2-1 .... centromere
,,, region 3 short arm chromosome .. 8
region ( ) ( ),,,, region ( .. 10 % )

bands
region .. bands .. Sequence of DNA band enzyme gene band locus bands ( Locus )gene
.. .. ..

8 P3,,,
: .. chromosome P ( short arm Q) Long arm
region .. bands ( 3 )
locus
dash dash = " - " ( deletion )
.. ( )
8P 2 23 ^313

313 locus band 23 region 2 short arm chromosome 8deletion
- anatomy chromosomes :
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INHERITANCE
1- Autosomal inheritance
- In one pair of autosomal chromosome Same anatomically but different in gene
genes anatomically
( Normal gene with pathological gene medicine ) 3
Normal gene on one and normal gene on other locus 2 identical loci ) genotype ( .. ) 2 identical gene on 2 identical loci ( homozygous
completely normal person clinically .. homozygous genotype
phenotype .. clinical manifestations normal phenotype So, here
2 pathological gene on 2 loci So, genotype homozygous
phenotype diseased
dominant or recessive gene Normal gene in one locus and pathological gene on opposite locus
So, genotype heterozygous
dominant or recessive pathological gene phenotype
* So, if phenotype diseased so pathological gene ( is dominant )
Hetero Homo dominant
* If phenotype normal so, pathological gene ( is recessive )
homo recessive
dominant Or recessive gene hetero
Autosomal dominant inheritance
3 .. pathological gene
.. items

Characters
1 - no sex difference ( as autosomal )
2- may be homo or hetero .
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.. ) D pathological gene ( D dominant

:
DD or Dd or dd
DD diseased ( phenotype )
Dd also, diseased
dd normal ( phenotype ) ( NO pathological gene )
- So, if phenotype = diseased So, heterozygous or homozygous

- And person with phenotypically free ( normal ) No pathological gene
3- so, unaffected persons are genotypically normal & phenotypically normal
4- one of the parents must be affected .
.. ) DD or Dd ( .. diseased
D from mother + D from father ) Homozygous ( DD diseased ..
diseased .. diseased
) heterozygous ( Dd diseased or free
.. d ..diseased D
( normal )
So, if any autosomal inheritance at least one of the parents is diseased
) ( mild disease .. dominant gene

,,, .. family history history .. spherocytosis
,,,,

Spherocytosis, VW disease, bone disease, achonodroplasia and oesteogenesis imperfecta
BA
AD inheritance criteria
spherocytosis ,,
:
1- new mutation :
which is very common new mutation teratogen
2- variable expression of the gene :
,,, ( May BA or allergic rhinitis or allergic sinusitis ( or any other atopic disease ) BA
Called variable expression of the gene .. )
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3- gene penetrance :
: gene factor ,,, .. environmental factors
,,, recessive or AD
G6PD deficiency antioxidant
( ) ,,, G6PD
,,, ,,, ,,, ,,, ( )
6 ,,, hemolysis
.. ..
.. gene penetrance

Need environmental factors .. ( )
( ,,, BA) bronchogenic carcinoma
4- illegal son
,,,, ,,, ,,
) AR ( Autosomal recessive gene inherita nce
Characters
items ..

1 - No sex differences
2- the affected person should be homozygous .
- Pathological recessive gene ( r )
:
RR or Rr Or rr
if RR normal
if Rr normal
only rr diseased
so, if pheotypically normal may be genotypically normal or carrier

but, if phenotypically diseased homozygous genotype
,,,
All inborn error of metabolism, thalassemia , sickle cell anemia, hemophilia
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3- so, unaffected persons ( phenotypically norma ) are either genotypically normal or hetero ( carrier )
4- both parents are carrier or one diseased & the othe is carrier .
: .. rr diseased diseased rr may both
) Or morbidity lethal r NB (
rr
hemosiderosis .. ) B- thalassemia major (
gonands ) B thalassemia major complications (

) diseased ( Rr
r consanguinity
) recessive pathological gene more common in cansanguant marriage (
,,,
,,, consanguinity
) ( 1st degree
Called 1st cousin or Second degree .. consanguinity
Called 3rd degree consanguinity Or 2nd cousin Non consanguant marriage ) ( 28
29 28
2- Sex chromosome i nherita nce

Y X gene Y X .. XY male XX female anatomically So, female XX both typically identical .. But, male XY
.. .. Y X

dominant or recessive
Homo or heterozygous male
) Either on X or Y( hemizygous .. 2
X - linked recessive gene
X pathological gene Page |
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XY Male XX female female .. diseased male affected X carrier as it is a recessive gene

common in males .. X - linked recessive As G6PD, Douchenne myopathy, hemophilia A and B
X - linked recessive
.. female Male XX
VS
XY
So, XX - XX - XY - XY
) ( female to male = 1: 1
G6PD pathological gene
,,,
Here father is diseased .. Mother is Normal
So, all daughters carrier
normal sons .. ) Male ( X
carrier genotype .. Normal phenotype ) ( females normal carrier
XY normal person .. ) diseased X ( XX
XX
XX
VS
XY
- XX - XY - XY :
:
1- genotype
( XY ( diseased Males .. ) XX ( carrier females
2- phenotype
All females normal .. 1/2 males diseased
diseased ,,, ,,,,,,
XX
XX
XX
VS
- XY
XY
XY :
:
1- Genotype
All females carrier
all males diseased
2- phenotype
all females normal
.. All males diseased

.. gene .. generations
) ) ( (
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generation diseased carrier

normal phenotype offspring diseased
.1
normal offspring Normal
.2
diseased carrier
.3
carrier diseased diseased
.4

females common in males G6PD
common in males ,,,
female ..
) homozygous diseased (
1- diseased father & the mother is carrier
carrier diseased 2- diseased mother & farher
diseased diseased XX
VS
XY
3- turner $ :
turner syndrome gene X female ,,, diseased carrier
4- new mutations :
So, carrier One gene .. homozygous .. normal X gene mutation fetus
New mutation in a carrier
5- lyon's theory
lyon's theory ..
XX
- XX : females -
So, both are genotypically carrier

Normal phenotype
diseased .. Phenotypically normal females nucleus .. Lyon nucleus X .. X nucleus
N .. ) non functioning ( condensation Barr body
female Barr body male
2 Barr bodies 3 X Extra X NB
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Nucleus
.. non functioning
Non functioning
( : ) .. X - chromosome .. .. Barr body pathological gene
.. Nucleus .. pathological genefunctioning
female pathological gene
( : ) X nucleus gene .. X Barr body
gene .. recessive ( dominant ) normal Barr body .. recessive ( dominant ) Barr body
So, lyon's theory say that :
Female may be Genotypically carrier ( XX ) but pathological gene X present on functioning X chromosome so,
phenotypically diseased
male .. female X
,,, male
female X gene gene Males X ,,, Males X - linked dominant
homo or hetero .. common in males females ,,, Barr body )
) Non functioning
1ry hypophosphatemic rickets3- Y - linked i nherita nce

Y Absolutely in males not in female gene pathological gene ( oncogenes ) more severe and common in males
genital system females
gene .. .. new mutation hairy ear pinna

4 - Co - domina nt inheritance
- .. dominant ..
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A .. B : A - B - AB - or O
BO :
VS
)- AB (AB ) - BO (B
AO
)AO (A
)OO ( O
5- Intermediated i nherita nce

.. dominant gene shperocytosis So, genotype is Either Dd or DD both are diseased
homo clinical picture More severe in homo than hetero .. hetero - recessive - rr .. thalassemia
Rr
..phenotype normal Called thalassemia minor mild anemia

6- Germline mosaicism
( family pedigree )
NB . about family pedigree
female
male
,,, ..
.. 3 ( )
( ) diseased
:
( ) normal geno and phenotype .. New mutation germ-line mosaicism
.. mosaicism ) germ cell ( abnormal cells .. ) somatic cell ( normal
germ line ( germ cell mutation germ cell )
7- mitochondrial inheritance
: .. ( X - linked recessive X - linked
) dominant
diseased Normal both normal genotype and phenotype
mitochondrial inheritance
mitochondria ) circular ( DNA ( ) as mitochondrial encephalopathy mitochondrial disaese
Ovum mitochondria sperm .. ovum ..
- ... .. sperm
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8 - Genetic he tero-genicity
differential diagnosis different genotype may cause same phenotype .. ) albinism ( ... albinism albinism
9- Multi factorial inherita nce
risk factor ) ( risk factor gene G6PD .... environmental factors
,,,
Mitochondria head of sperm
ovum Mitochondria in tail only
C hromos omal aber ration

Etiology
etiology
.. germ line mosiacism
1- Old maternal age
abnormality .. 2- May viral infection
,, ) gonadal cells ( Auto immune disease
3- Teratogen drugs
gonadal cells 4- May exposure to irradiation
gonads 5- May transmitted

6- May gene factor
- As fragile X - chromosome
Mechanisms

A - Non disjunction
failure of separation of 2 homologous chromosomes ) ( 95 % commonest : meiosis .. cell division 46 meiosis
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1- In 1st meiotic division

.. cells ) (
.. chromosomes centeromere centeriole fibers 23 .. chromosomes 2- 2nd meiotic division :
23 4 .. mitosis
( 46 chromosome zygote
.. ) X ( fertilization sperm ovum )

non dis junction
centriole fibers ,,, teratogen

) teratogen ,, viral drug teratogen (
22 chromosome 24 chromosome 2 So, 2 ova formed 1st contain 22 chrosomes & the 2nd contain 24 chromosomes
: zygote 1- if sperm ( contain 23 chromosomes ) fertilize 1
st
ovum ( that contain 22 ch. ) so, zygote = 45 ch.
chromosome 2 chromosomes 45 zygote

21 monosomy
So called , monosomy 21
If 13 called monosomy 13 etc
21 sperm ) 21 ( chromosome Ovum
monosomy 21 ..
2- if sperm ( contain 23 chromosomes ) fertilize 2 nd ovum ( that contain 24 ch. ) so, zygote = 47 ch.
) 21 ( 2 chromosome ovum sperm 2 1 .. 21 3
So, called trisomy 21 , trisomy 13 .etc.
Monosomy or trisomy non disjunction X .. early abortion Monosomy ..
turner syndrome
.......trisomoy 13 Down syndrome 21 .. trisomy
) old maternal age ( .. chromosomes normal 29
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29 30
Mechanism
B - Breakage
chromosomes :
Short arm that has 2 regions
Long arm that has 3 regions
mechanism region .. region short arm

1 - Deletion means Broken part is deleted ( lost) ..
genetics .. " " dash genetics chromosome 9 P 2 - 9
deletion region short arm chromosome
5 P -
deletion short arm chromosome .. 5
21 Q -
deletion Long arm ) 21 ) anti mongolism
4 P - ..
deletion short arm 4
2- transloacation :
paired
- paired chromosome
( another
) acrometacentric
short arm Called translocation ( short ) .. ) t small ( t

chromosome .. 20 10 short arm
( .. )
tp (10 - 20 ) means translocation of short arm between 10 & 20 chromosome
10 ( 20 ) 10 ,,,,, 20
2 long arms 2 short arms ..
) tp ( 10 - 20 ) + t Q ( 10 - 20
2 balanced translocation carrier balanced translocation carrier
.. 2 ( 2 acrocenteric chromosome short arms )
,,
- short arm
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( .. ,,, .. )
Long arm long arm .. 45 46 functionally .. Called balanced translocation carrier
,,, generations
3- Inversion :
.. .. Called inversion " in " ( IN SMALL LETTERS ) genetics
4- ring chromosome :
chromosome short arm .. long arm
( ) .. Called ring chromosome karyotyping C - ISo- chromosome formation :
.. 1st meiotic division .. 23 meiosis 2nd mitosis chromosomes .. fibers chromatid .. 2
chromatid centromere
chromatid
( ( ) )
.. iso chromosome fibers short arm Long arm ..
chromatid .. short arm short arm long Long arm ( ) 2 short ,,, centromere

regions short ).. )Mirror shape iso chromosome

,,,,
fertilization zygote : 1- With 3 short arms + 1 long arm

3 short arms
1 long arm
2- Or With 3 long arms + 1 short arm
iso chromosome iis
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Classification of chromosomal aberration

,,,
1- Numerical :
A - May defect in 1 paired chromosome
called an euploidy ,,, .. Monosomy trisomy & both are Due to non disjunction
1- autosomal trisomy 21 ) Down $ ( , trisomy 13 .etc

2- sex chromosomes :
a- X chromosome 3 X super female
may XXY klienfilter syndrome
b- Y chromosome XYY super male
turner syndrome monosomy B - All paires of chromosomes
: Called polyploidy a- triploidy :
Called triploidy 2 sperms fertilization ovum as in vesicular mole 69 chromosomes 3
Early abortion
b- tetraploidy :
mitosis .. 2 zygote chromatid .. 2 chromatid chromosomes
chromosome

) .. ( Failure of separation of cell called tetraploidy 4
2- Structural as :
Deletion
Ring chromosome
Translocation
Isochromosome
duplication ) 3 1 ( 3 1 region chromosome Page |
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,, breakage .. 2 identical chromosomes

( region 1 - 2 - 2 - 3 ) 1 - 3
translocation
3- Mosaic :
structural ..Numerical called mosaicDow n s yndrome

.. Down Down 3 of chromosome 21 Which is acrocentric chromosome And also, short chromosome
short arm ,,,
short arm ( )
= ) Types ( cytogenic type
mechanism
) 1- Non disjunction ( Very common
- failure of separation of chromosome 21 .. So, zygote contain 2 of 21
( 46 .. ) zygote 47 95 % of Down is non disjunction type .
incidence with age of mother
( .. 35 )
,,, 36 0.5 % Down
3
) So, 39 years 1 % , 43 years 2 % & 45 years 0 % ( Menopause
2- Translocation
Represents 4 % of Down
stem cell testes ovary .. 21 13 short arm 2113 Long arm Translocated .. 21 Long arm 13
Balanced translocation carrier 45 chromosome
) by 1st meiotic devision ( 2 gametes Long arm 21 long .. 13 13
21
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.. ..
46
2 of 13 + 2 of 21 + 42 others ..
21 13 : 42 other chromosomes + 1 of 13 + 1 of 21 + one adhesied 13&21 = 42 + 3 = 45 chromosomes

45 ..
( : ) 46 .. ( ) 23
23 ..
) 42 others + 2 of 13 + 2 of 21 give 2 (21 others + 1 of 13 + 1 of 21 = 23 chromosomes
.. 42 others + 1 of 13 + 1 of 21 + 1 adh. 45So, give 2 cells .. 1st one contain 21 others + 1 of 13 + 1 of 21 = 23 chromosomes
& other cell contain 21 others + 1 adh. = 22 chromosomes
A1 .. A2 :A1 = 21 others + 1 of 13 + 1 of 21 = 21+1+1=23 chromosomes
A2 = 21 others + 1 adheised ( 13&21 ) = 21+1 = 22 chromosomes
( ,,, )..
2 of 21 .. 2 of 13 stem cell
,,, long arm
21 long arm 13
stem cell2 gametes

13 21 Long arm 21 Long arm 13
:
.. 42 others + 2 of 13 + 2 of 21 :
21 13 ..
B1 & B2
B1 = 21 others + 1 of 13 = 21+1 = 22 chromosomes
B2 = 21 others + 1 of 21 + 1 adhesied ( 13&21 ) = 21+1+1= 23 chromosomes
..
B2 = 21 others + 2 of 21 + 1 of 13
,,,
stem cell 2 of 13 2 of 21
,,,
long arm ,,, 13 Long arm 13 long of 21
13 Long arm Long 21
21
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:
: .. 42 others + 2 of 13 + 2 of 21
.. 21 13
C1 & C2
C1 = 21 others + 1 of 21 = 21+1 = 22 chromosomes
C2 = 21 others + 1 of 13 + 1 adhesied ( 13&21 ) = 21+1+1= 23 chromosomes
..
C2 = 21 others + 2 of 13 + 1 of 21
) sperm Ovum ( Other gametes
gametes
) ) testis ( Sperm ( 21 13
) Functionally 46 .. 45 stem cells (
S sperm S = 21 others + 1 of 13 + 1 of 21 = 21 + 1 + 1 = 23 chromsomes
..
: .. ..
: ) (
A1 = 21 others + 1 of 13 + 1 of 21 = 21+1+1=23 chromosomes
A2 = 21 others + 1 adheised ( 13&21 ) = 21+1 = 22 chromosomes
B1 = 21 others + 1 of 13 = 21+1 = 22 chromosomes
B2 = 21 others + 1 of 21 + 1 adhesied ( 13&21 ) = 21+1+1= 23 chromosomes
..
B2 = 21 others + 2 of 21 + 1 of 13
C1 = 21 others + 1 of 21 = 21+1 = 22 chromosomes
C2 = 21 others + 1 of 13 + 1 adhesied ( 13&21 ) = 21+1+1= 23 chromosomes
..
C2 = 21 others + 2 of 13 + 1 of 21
& S = 21 others + 1 of 13 + 1 of 21 = 21 + 1 + 1 = 23 chromsomes
NB. Normal cell ( = N ) = 42 others + 2 of 13 + 2 of 21 = 46 chromosomes
) Z zygoute ( : zygote fertilization 1- S Vs A1 normal
- A1 = 21 others + 1 of 13 + 1 of 21 = 21+1+1=23 chromosomes
- S = 21 others + 1 of 13 + 1 of 21
So, Z = A1 + S = 42 others + 2 of 13 + 2 of 21 = N = 46 chromosomes
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..
2- S Vs A2 normal but balanced translocation
- A2 = 21 others + 1 adheised ( 13&21 ) = 21+1 = 22 chromosomes
- S = 21 others + 1 of 13 + 1 of 21
So, Z = 42 others + 1 adheised + 1 of 13 + 1 of 21 = 42+1+1+1 = 45
: zygote .. ) Balanced translocation carrier( 2 .. 21 2 13 2
3- S Vs B1 monosomy 21
- B1 = 21 others + 1 of 13 = 21+1 = 22 chromosomes
- S = 21 others + 1 of 13 + 1 of 21
So, Z = 42 others + 2 of 13 + 1 of 21 = 21+2+1=45 = monosomy 21
4- S Vs B2 trisomoy 21
- B2 = 21 others + 1 of 21 + 1 adhesied ( 13&21 ) = 21+1+1= 23 chromosomes
- S = 21 others + 1 of 13 + 1 of 21
So, Z = 42 others + 2 of 21 + 1 of 13 + 1 adheised = 42+2+1+1=46
: ) Down $ ( trisomy 21 21 3 13 2 (Down contain 46 chromosome But functionally 47 )
5- S Vs C1 monosomy 13
- C1 = 21 others + 1 of 21 = 21+1 = 22 chromosomes
- S = 21 others + 1 of 13 + 1 of 21
So, Z = 42 others + 2 of 21 + 1 of 13 = 42+2+1=45=monosomy 13
6- S Vs C2 trisomy 13
- C2 = 21 others + 1 of 13 + 1 adhesied ( 13&21 ) = 21+1+1= 23 chromosomes
- S = 21 others + 1 of 13 + 1 of 21
So, Z = 42 others + 2 of 13 + 1 adheised + 1 of 21 = 46
: trisomy 13 13 3 21 2 (contain 46 chromosome But functionally 47 )
: .. ..
,,,
Zygote formation 2 of 13 and 1 of 21 Monosomy of 21
,,,
2 of 13 and 3 of 21 Trisomy of 21 (Down contain 46 chromosome But functionally 47
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)
46 functionally 45 non disjunction 46 47
,,,
Zygote 2 of 21 + 2 of 13
2 ( ) Balanced translocation carrier zygote
,,,
.. 2 of 21 + 2 of 13 Normal
,,
- zygote 2 of 21 + 3 of 13 Trisomy 13
,,,
- Zygote 2 of 21 + 1 of 13 Monosomy of 13
21 ( balanced translocation carrier ) other chromosome

:
1- 25 % Down
2- 25 % balanced translocation carrier
3- 25 % normal
4- 25 % trisomy of the chromosome
( monosomy 13 21 ) early abortion
.. % 25 Down .. % 33 trisomy
: -1 Other trisomy25 %
-2 33 %
survey ) 21 adhese to other chromosome( balanced translocation carrier Down ) As actual risk incidence( 10 - 15 %
25 %
Down anomalies () Early abortion balanced translocation carrier survey 2 - 5 %
25 %
sperm Down .. extra chromosome motility sperm fertilization
" "
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2 long arm 21 .. 21 21 gametes .. 2 of 21 ..

,,, sperm fertilization
) ( Monosomy 21 .. 21 gametes Down Trisomy of 21 .. 2 of 21 gamete balanced .. abortion ) ( .. 100 % Down
translocation
.. 3 of 21 sperm ) ( ) 21 sperm (
.. abortion monosomy of 21

History of repeated abortion May balanced translocation of husband
3- Mosaic mongol 1 % :
.. trisomy 21 Normal
31 30
,,,
.. balanced translocation carrier
,,, .. ) 2 ( translocation ,,,
No abnormality could be detected
General clinical presentation of any autosomal chrosomal disorders
1- Mental retardation
) ( idiot ,,, degrees sphincter control 2- Growth retardation
history .. 3- All brain sized microcephaly
All in head circumference
4- May multiple congenital anomalies
Multiple anomaly .. stress disorder ..
a- Eye
May micro ophthalmia

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Cataract or glaucoma
b- May lip anomaly
Cleft lip , Cleft palate Or both
c- Congenital heart disease
In Down common AV canal
Trisomy 13 left to right shunt ,,, midline defect
d- Hernias
Umblical or inguinal
Hypotonia
e- Genital anomalies
May as bilateral un descending testis called cryptochidism

Unilateral un descending testis
d- Limb anomalies
Poly dactyl ( )
Rocker bottom heel

complete dorsiflexion ,,, .. ) heel ( .. foot
complete dorsiflexion
) .. anomalies (
Specific manifestations in Down syndrome
clinical pictures

Associated anomalies
1.
Congenital heart disease
2.
GIT anomalies
Pyloric stenosis
May dudenal atresia
May congenital megacolon
3.
Renal anomalies : as
Polycystic kidney
Or Ptosed kidney ( in pelvis )
Or horse shoe kidney
4.
Anomalies in thyroid
May associated with autoimmune thyroiditis ( Hashimoto's )

Causes of death in Down
1- Associated anomalies as :
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Renal failure
Congestive heart failure
2- Associated repeated infection

) acrobatic sign ( .. severe hypotonia
Weak respiratory muscles Ptosed liver and spleen hernia ) (
,,,,,
Causes of repeated infections in Down syndrome
chest infection
1) Hypotonia
Shallow respiratory movement + weak cough reflex
2) Congenital heart disease
Lung congestion and plethora
3) Associated T cells dysfunction
So, humoral and cell mediated immunity
N.B. Incidence of leukemia
20 normal
& Leukemia cause immunity
4) so, Leukemia incidence of infections
3- Mental retardation
..
4- Leukemia

5- Un explained sudden death.
Hand clinical pictures
A - sedni crease , complete simian crease or incomplete Simian crease :
: 3 main crease
1- longitudinal crease
2- proximal horizontal crease
) lateral 2 ( thumb hand
Distal horizontal crease medial side - 3
Down
called sedni crease .. proximal horizontal Page |
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Called complete simian crease proximal distal Normal ) ( another crease complete simian crease partial flexion
Called incomplete Simian crease
B - brachy dactyl
C - rudimentary middle phalanx of little finger .
rudimentary middle phalanx 2 crease only Little finger D incline dactyl
Called inclino dactyl Investigations
1 In all genetics Karyotyping
clinical diagnosis Down Karyotyping cytogenic type of Down non disjunction ) 21 3 ( 47 -
translocation 46 -
mosaic pattern 47 46 -
2 Chest X ray
,,,,
Down X ray chest and heart
) ( congenital heart disease -1
Pneumonia chest infection -2
) If associated with leukemia( enlarged mediastinal lymph nodes -3
retro sternal goiter ... May associated Hashimoto's thyroiditis
.. -4
3 Investigations for Leukemia

bone marrow examination .. 6 CBC .. leukemia
BM examination for early detection of leukemia
4 Thyroid function
thyroid
5 Sonar on abdomen
6- ECG and ECHO
heart
7 Barium study
8 - IQ for associated MR
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Treatment
No thing .. Only special care and supportive treatment
What about future pregnancy ???
,,,

Karyotyping
.. ) non disjunction ( 47 ) 35 ( Down
trophoblastic biopsy .. Down
-1
,,, .. ) ( amniocentesis ) 6 - 8 (
12 induced abortion ( abortion Down
)
abortion .. 6 - 8 trophbalstic
abortion 13 14 .. amniocentesis -2
contraceptive ,,,
trohpobalastic ,,, ) ( extra chromosome 46 karyotyping Non disjunction .. other 21
) (tubal ligation .. 21 21
Tris omy 13

karyotyping amniotic fluid NB
3 13 karyotyping ,,,
Enumerate autosomal chromosomal aberration and discuss one of them ??
Down Most common
Types
As Down with same risk factors ( as Down (
Clinical pictures
1.
Mental retardation
2.
Growth retardation
3.
Microcephaly
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4.
Multiple congenital anomalies

3 ,,, .. general
A- All defects are Midline defects

- Eye
called cyclopia May single eye
- Nose may single nostril called cebocephaly ) (

- May cleft lip and cleft palate
- May thyroglossal cyst
- May heart defects Midline defects ( VSD, ASD and PDA )
- Umblical hernia
- May absent of anterior abdominal muscles
palpation organs
- Genital defects
hypospedius + Un descending testis
B- ?????? polydactyly
C- Capillary hemangioma
Investigations
Karyotyping + investigate anomalies
Treatment
As Down
Leukemia
Tris omy 18 ( Edward sy ndrome )
Types
As Down
Clinically
+
Specific manifestations
1- Hyper tonia
) cerebral palsy ( CP
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In trisomoy 13 may hypo , may hyper
Down hypo
2- Prominent occiput
3- Ears
Low set ears .. Down
tragus .. Lateral angle of the eye .. ) chromosomal ( Down ear
malformation + Low set ear 18 4- Hands Clinched fist
Hypertonia
Overlapped palm middle ring
5- Rocker bottom heel
Investigations and treatment
As Down
cri-du-chat -sy ndrome = 5 P Deletion of short arm of 5th chromosome
Called cri-du-chat-syndrome
Clinical Manifestations
3 +
1- Round face
2- Marked hypertelorism
3- Cat like cry
due to laryngeal hypoplasia
Investigations
Karyotyping
Treatment
Supportive treatment
a nti mongolism
= 21 Q -
Deletion of long arm of chromosome 21 .. Called anti mongolism

Clinically
+
1- Hypertonia
2- downward slanting of the eye :
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- In Down low set ear ( ) Upward slanting of the eye

medial angle lateral angle
) downward slanting of the eye( lateral angle Medial angle .. 3- Prominent nasal bridge
Down
4- Large ear
Down
Investigations
Karyotyping
Treatment
Supportive
Sex chromos omal aberration

turner s yndr ome
Y chromosome .. male embryo
no formation of male genital system .. Y chromosome female
only one X chromosome .. turner syndrome So, no Barr body X X ( Only one short arm and one long arm )
Criteria
:
1 ) Female as there is no Y chromosome
2 ) Short stature

) 4 ( sex chromosome
2 on each X if female Or 2 on X and 2 on Y if male
2 .. 2
3 ) Abnormal somatic features
1- Webbing of the neck fold of skin around the neck .
2- Wide spaced nipple :
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out side mid clavicular line at mid clavicular line Nipple So, wide spaced nipple
3- Congenital heart disease :
coarctation of Aorta
4- wide carrying angle :
radius Ulna .. radius and ulna forearm
Carrying angle trunk .. full supination
radius
So, wide carrying angle
elbow .. pronation
5- genreralized non biting odema at birth
sonar Intra uterine lymphatic .. non biting .. generalized edema
lymphatic hypoplasia 6- triangular face
forehead chin triangular face 7- No menstruation No 2ry sexual character
15 -13 infertile fibrotic ovary .. ovary sonar
turner
1- deletion of short arm of one of X chromosome ( 46 XX P - )
Barr body buccal smear ) 46 XX P - ( deleted X short arm
deletion of short arm of one of X chromosome
ovarian function turner - normal menstruation , Normal 2ry sexual character & normal menopause
X Lyon ) ( function of the ovary Barr
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long arm -
32
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2- deletion of long arm ( 46 XX Q - )

) ( female .. deletion of long arm .. 46 XX Q - ) ( fibrotic ovary
no menstruation , no 2ry sexual character

1ry infertility turner
3- mosaic turner :
) ( mosaic turner ... X 45 .. Menopause
,,,
turner
turner )Deletion of short arm only( XX P - mosaic

Investigations
1.
Buccal smear no Barr body
2.
estrogen as fibrotic ovary
3.
FSH & LH ( pituitary gonadotrophins ) ( no ve feedback )
4.
Sonar fibrotic ovary
5.
Diagnostic karyotyping
Treatment
1- for short stature give growth hormone

2- Hormonal replacement therapy .. for 2ry sexual features
) but still infertile ( female
clinical features of Down on data show
31 1:34
1- skull circumference microcephaly
2- Fine hair
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3- Brachycephaly ( occiput flat )
4- Eye :
- depressed nasal bridge and medial epicanthus So, apparent convergent squint.
- upward slanting of the eye
) ( medial angle Lateral angle .. Down
- Micro ophthalmia
- Iris brush field iris
with line of demarcation Iris
5- Scrotal tongue means prominent rogue on the tongue
) Scrotum tongue (
.. .. ) ( micrognathia
tongue suckling ..
hypertrophy of papillae of tongue from prolonged suckling
6- In hands
- Simian crease
- Inclino dactyl
- Brachydactyl
7- wide space between big toe and other toes:
wide space between big toe and other toes ..

8- On sole :
deep grove opposite space between big and other toes
9- Acrobatic sign due to severe hypotonia
) 1886 Down NB (
Trisomy 13 also, on data show
- Marked micro ophthamia
- May single eye
Nonann syndrome
1963 - turner -
32 31
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,,,
.. ,,, female Short stature, webbing of neck + skeletal deformity

: turner syndrome
,,, ,,
:
,, ,, ..
,, turner
mosaic turner
46 XX P -
( )
gametes .. 1st meiotic 23 gamete X ( ) 2nd meiotic division mitosis fibers

fibers .. short arm Long arm
2 gametes short Long short arm short Long arm long fertilization gametes ( X )
turner phenotype .. 1 short arm 2 short arms2 long arms
So,
) 1- if gamete with 2 short arm fertilized by normal gamete ( 1 short and 1 long
3 short arm + 1 long ..
2 short 4 .. 3 short 6 So, tall female
Long arm .. ) Degenerated ovary no 2ry sexual characters (Fibrotic ovary
) 2- or gamete with 2 long arms fertilized by nomral gamete ( normal gamete contain 1 long + 1 short
So, net result 1 short + 3 long
webbing coarctation skeletal deformity
35

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) ( + So, appearance of 2ry sexual character 3 long ) Long fertility age( menopause
) long .. support 3 ovary .. ovary degeneration (
: turner turner
Due to iso chromosome of the long arm of the X chromosome
) ( turner features .. turner
Called Nonann syndrome
turner Nonann
Etiology
turner
nonann
chromosomal disorder
autosomal recessive gene defect
( 1 X, 1 short arm or iso chromosome

long arm )
Sex
Must be female
male or female
Mentalitity
normal
variable degrees of MR
Congenital heart disease
Coarctation of the Aorta
congenital pulmonary stenosis
Fertility
Classic type infertile
fertile
Karyotyping
Abnormal
normal
MR Nonann
,,,
severe MR .. mild MR ,,, :
illegal pregnancy
Intra uterine criteria of turner
Generalized edema
heart failure Hydrocephalus edema After delivery

1.
Triangular face
2.
Coarctation of Aorta
3.
Webbing in neck
4.
Dorsum of hands and foots non pitting edema

monosomy 95 % of turner N.B.
5 %
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Klinefelter sy ndrome
2 X + 1 Y So, 47 XXY
Male as there is Y
Y 2 X 2 ) 6( So here , tall stature
- has 2 X so, More ovarian genes Cause atrophy of testis ( degeneration of gonadal cells )
) short .. X long arm ovarian gene (
- No somatic deformities
..
..
1- No 2ry sexuall characters :

Other sex testosterone .. ) .. (
) (
2- fat with female distribution of fat
fat muscle Klinlfelter .. fat muscle
and
female distribution of fat ( buttocks & breast (gynecomastia ) )
3- Feminine behaviour
) same sex ( Homosexual 30 %
Investigations
1.
Buccal smear Barr body
2.
testosterone level
3.
FSH & LH
4.
Fibrotic testis
) ovary (
5.
Karyotyping 47 XXY
) X 2 ( 48 XXXY .. calssic 47 XXY

But only emotionally affected ) ( normal mentality 47 XXY
female behaviour .. -
Y X female ) heart neuronal cells (

:
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.. brain decesions dominate heart decesions

,, ( ..
)
..
( ) .. ..
100 5
( .. ) : .. female ..
NB chromosome X Mental retardation turner MR
( .. x )
?? Enumerate chromosomal disorders that cause MR

- all autosomal
... sex chromosomal disorders turner .. .. .. turner female attitude ( male X .. )
.. superfemale
,, Klinfelter Mosaic
Treatment
testosterone somatic features

Superfemale , supermale & fragile X $
In born eror 50 32 phenyl kentonuria and galactosemia

38

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www.facebook.com/dr.tafreegh

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Genetics - DR Abo-ElAsrar - by El Azhar Medical Students 2012

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Genetics - DR Abo-ElAsrar - by El Azhar Medical Students 2012

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( BETA EDITION)

Geneti cs Dr. Abo -Asrar

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Geneti cs Dr. Abo -Asrar

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Geneti cs Prof. Dr. Abo El-Asrar

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Geneti cs Prof. Dr. Abo El-Asrar

chromosome ( 2 chromatids ) when no cell division ,,,, ... ..

region ( ) ( ),,,, region ( .. 10 % )

" " : ,, : " " "

Geneti cs Prof. Dr. Abo El-Asrar

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Geneti cs Prof. Dr. Abo El-Asrar

.. ) D pathological gene ( D dominant

dd normal ( phenotype ) ( NO pathological gene )

- So, if phenotype = diseased So, heterozygous or homozygous

) ( mild disease .. dominant gene

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Geneti cs Prof. Dr. Abo El-Asrar

so, if pheotypically normal may be genotypically normal or carrier

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Geneti cs Prof. Dr. Abo El-Asrar

2- Sex chromosome i nherita nce

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Geneti cs Prof. Dr. Abo El-Asrar

XY Male XX female female .. diseased male affected X carrier as it is a recessive gene

all males diseased

.. All males diseased

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Geneti cs Prof. Dr. Abo El-Asrar

generation diseased carrier

normal offspring Normal

carrier diseased diseased

So, both are genotypically carrier

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Geneti cs Prof. Dr. Abo El-Asrar

1ry hypophosphatemic rickets3- Y - linked i nherita nce

" " : ,, : " " "

Geneti cs Prof. Dr. Abo El-Asrar

5- Intermediated i nherita nce

..phenotype normal Called thalassemia minor mild anemia

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Geneti cs Prof. Dr. Abo El-Asrar

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Geneti cs Prof. Dr. Abo El-Asrar

1- In 1st meiotic division

.. ) X ( fertilization sperm ovum )

centriole fibers ,,, teratogen

ovum ( that contain 22 ch. ) so, zygote = 45 ch.

chromosome 2 chromosomes 45 zygote

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Geneti cs Prof. Dr. Abo El-Asrar

Long arm that has 3 regions

mechanism region .. region short arm

short arm Called translocation ( short ) .. ) t small ( t

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Geneti cs Prof. Dr. Abo El-Asrar

fertilization zygote : 1- With 3 short arms + 1 long arm

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Geneti cs Prof. Dr. Abo El-Asrar

Classification of chromosomal aberration