genetics - dr abo-elasrar - by el azhar medical students 2012

8/13/2019 Genetics - Dr Abo-ElAsrar - By El Azhar Medical Students 2012

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( BETA EDITION)

With

Prof. Dr Mohammed Abo El-Asrar

Edited By

El-Azhar Medical students 2012


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Genetics Dr. Abo-Asrar

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Genetics INDEXTotal pages = 39

Total time = about 6.5 hours

number Paglecture 28 4 -

basics ( page 4 )

inheritance 6 ( Autosomal inheritance 6 )

lecture 29 10 -

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 )

lecture 30 17

cont. mechanisms ( page 16 )Classification of chromosomal aberration ( page 18 )Down syndrome ( page 19 )

- lecture 31 24 -

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 )

lecture 32 29

cont. turner ( page 35 )

Klinefelter syndrome ( page 37 )


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Genetics Dr. Abo-Asrar

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: : : : :

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.. Items sub items .. .. .. .. . .. .. ..

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Genetics Prof. Dr. Abo El-Asrar

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8Genetics

- - -:

Inheritance Chromosomal abnormalities

Basics basics 46....So, called 23 pairs of chromosomes

2 ( sex )22 pairs ( autosomal ) + 1 pair22 pairs ()Called autosomal chromosomes

1 pairsex chromosomeMay beXX orXY

- natomyhromosome DNA mitosismeiosis..metaphase chromatid by centromerecentromerechromosome(Short arm and long arm)short arm(.. ) P..long armQ chromosomes..

Long , Short & Medium size chromosomeX.. Y chromosome

entromere : centromerecentromereshort and long arm..Metacentric chromosomebeside the center long and long arm Centromere in extremities Acro - centric chromosome ( acro means ) short arm 21, 18, 22.... if between 1 & 2 ( ) called Sub metacentric chromosome


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chromosome (2 chromatidswhen no cell division .. ... (.. ) - arm(Electron microscope..)9

() regionarm..region ..centrome....1-2-3-4

,,region3 short armchromosome8.. - egion

( ( ) ) region ( 10 %.. ) bands

regionbands.. - bandSequence of DNA..enzymegene bandlocus

bandsLocus(gene) .. .. .. ,,8 P3 : chromosome..Pshort arm(Q Long arm) region ..bands ( 3) locusdasdeletion("dash = " -) .. ( )

8P 2 23 ^313 locus313band23region2short arm chromosome8deletion anatomychromosomes :


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INHERITANCE1- Autosomal inheritance

- In one pair of autosomal chromosome Same anatomically but different in gene

natomicallyenesmedicineNormal gene with pathological gene( ) 2 identical lociNormal gene on one and normal gene on other locus

homozygous(2 identical gene on 2 identical loci( .. ) genotype) genotypehomozygous..clinicallycompletely normal person clinical manifestations.. phenotypeSo, herehenotypeormal

2 pathological gene on 2 lociSo, genotype homozygous

phenotypediseased

- eneominant or recessive

Normal gene in one locus and pathological gene on opposite locus

So, genotypeheterozygous

phenotypepathological genedominant or recessive* So, if phenotypediseased so pathological gene ( is dominant ) ominantomoetero

* If phenotypenormal so, pathological gene ( is recessive )

ecessiveomo ominant Or recessiveene etero

Autosomal dominant inheritance athological gene.. items..

Characters-no sex difference ( as autosomal )

may be homo or hetero .


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dominant D(pathological geneD.. ) :DD or Dd or dd

DD diseased ( phenotype )

Dd also, diseaseddd normal ( phenotype ) ( NO pathological gene)

So, if phenotype = diseased So, heterozygous or homozygous

And person with phenotypically free ( normal ) No pathological gene so, unaffected persons are genotypically normal & phenotypically normal

- one of the parents must be affected . diseased.. (DD or Dd.. ) diseasedDD(Homozygous)D from mother + D from father diseased.. diseased Dd(heterozygous) ..seased or free d .. Ddiseased

( normal )

So, if any autosomal inheritance at least one of the parents is diseased dominant gene..mild disease() historyfamily history.. spherocytosis.. ,,,,

Spherocytosis, VW disease, bone disease, achonodroplasia and oesteogenesis imperfectaBA AD inheritancecriteria spherocytosis :new mutation :

-new mutationwhich is very commonteratogen

variable expression of the gene :

- BAMay BA or allergic rhinitis or allergic sinusitis ( or any other atopic disease )( )..Called variable expression of the gene


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gene penetrance : :gene factor .. environmental factors ,,recessive or AD G6PD deficiencyantioxidant )G6PD )() 6hemolysis .. .. ..gene penetrance Need environmental factors

..( ) ( BAbronchogenic carcinoma)- illegal son

AR ( Autosomal recessive gene inheritance )

Charactersitems..

- No sex differences

the affected person should be homozygous .

Pathological recessive gene ( r ) :RR or Rr Or rr

if RR normal

if Rr normal

only rr diseasedso, if pheotypically normal may be genotypically normal or carrierbut, if phenotypically diseased homozygous genotype

All inborn error of metabolism, thalassemia , sickle cell anemia, hemophilia


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so, unaffected persons ( phenotypically norma ) are either genotypically normal or hetero ( carrier )

- both parents are carrier or one diseased & the othe is carrier . diseasedrr.. :may bothrr diseased

(NB rlethalOr morbidity) rr ( B- thalassemia major.. )hemosiderosis complicationsB thalassemia major)gonands Rr(diseased) consanguinityr

(recessive pathological gene more common in cansanguant marriage)

,,,onsanguinity ,,,

st degree( ..Called 1st cousin or Second degreeconsanguiCalled 3rd degree consanguinity Or 2nd cousin ()Non consanguant marriage

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2- Sex chromosome inheritancegeneXY femaleXXmaleXY..X Y anatomically

So, female XX both typically identical .. But, male XY

XY.. .. ominant or recessive maleHomo or heterozygous 2.. hemizygous(Either on X or Y)

X - linked recessive gene pathological geneX


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femaleXXMaleXY Xaffectedmalediseased..femalecarrier as it is a recessive gene common in males X - linked recessive..

As G6PD, Douchenne myopathy, hemophilia A and BX - linked recessive -Malefemale..

XX VS XY

So, XX - XX - XY - XY

female to male = 1: 1() pathological gene G6PD Herefather isdiseased .. Mother is Normal

So, all daughterscarrier

X (Male.. )sonsnormal-emales( henotypeormal..enotypearrier carriernormal

XX( diseased X) ..normal personXYXX VS XY :XX - XX - XY - XY :

genotype )femalescarrier(XX.. )Malesdiseased(XY phenotype

All females normal .. 1/2 malesdiseased

diseased XX VS XY - :XX XX - XY XY :

Genotype

All females carrier all males diseased phenotype

all femalesnormal .. All males diseased

generations..gene ..

( ( ))


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carrierdiseasedgenerationnormal diseasedoffspringphenotype Normaloffspringnormal carrier diseased diseased diseased carrier G6PDcommon in malesfemales ,,common in males female..

omozygousiseased)diseased father & the mother is carrier

- diseased carrier diseased mother & farher diseased diseased-

XX VS XY

turner $ :

femaleXgeneturner syndrome carrier diseased- new mutations :

- .. One geneSo, carrierfetusmutationnormal X gene..homozygous

New mutation in a carrier

lyon's theory ..lyon's theory females:XX - XXSo, both are genotypicallycarrier

phenotypeNormal femalesPhenotypically normal.. diseased Lyon.. nucleusnucleusX..X nucleus condensation(non functioning.. )N

Barr b

maleBarr bodyfemale 3 X2 Barr bodiesNB Extra X


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ucleus..on functioning on functioning ( : X - chromosome.. .. Barr body.. pathological gene Nucleus..pathological gene..

functioning

emaleathological gene ( : X nucleusgene..X Barr body generecessive..dominant(normal)Barr body ..recessive dominant( Barr body)

So, lyon's theory say that :X) but pathological gene Xpresent on functioning X chromosome

phenotypically diseased malefemale.. X male femaleX genegene-MalesX Males

X - linked dominant

-homo or heterocommon in males..femalesBarr body )Non functioning)

-1ry hypophosphatemic rickets3- Y - l inked inheritance

Y geneAbsolutely in males not in female pathological gene oncogenes() more severe and common in males

genital systemfemales gene .. new mutation..hairy ear pinna

4- Co - dominant inheritance ..dominant ..


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AB.. :A - B - AB - or O :AO VS BO OO ( O) - AO (A) - AB (AB ) - BO (B)

5- Intermediated inheritancedominant gene..shperocytosis

So, genotype is Either Dd or DDboth are diseased homoclinical picturehetero..More severe in homo than hetero recessivethalassemia..Rr - rr phenotype normal.. mild anemiaCalled thalassemia minor6- Germline mosaicism

)family pedigree(NB . about family pedigree

-malefemale ..((..3

( diseased) : ( normal geno and phenotype) ..New mutationmosaicismgerm-line mosaicism.. normal(somatic cell.. )abnormal cells(germ cell)

germ linegerm cell mutation(germ cell )7- mitochondrial inheritance : X - linkedX - linked recessive ( ..

dom) diseasedNormalgenotype and phenotypeboth normal itochondrial inheritance mitochondriaDNA(circular) mitochondrial disaeseas mitochondrial encephalopathy) Ovummitochondriasperm.. ovum

. sperm.....


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8- Genetic hetero-genicity differential diagnosis ..different genotype may cause same phenotypealbinism... (albinism)

albinism 9- Multi factorial inheritance

)risk factorgenerisk factor( -environmental factors.... G6PD

,,, head of spermMitochondriaMitochondria in tail onlyvum

Chromosomal aberration Etiology

tiology germ line mosiacism.. Old maternal age

- ..abnormality May viral infection

- Auto immune disease( gonadal cells) Teratogen drugs

-gonadal cells- May exposure to irradiation

-gonads May transmitted May gene factor

- As fragile X - chromosome

Mechanisms- Non disjunction failure of separation of 2 homologous chromosomes commonest95 %( )

-ell division..eiosis: meiosis46


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In 1stmeiotic division

- cells..( ) centeriole fiberscenteromerechromosomes..

23 ..chromosomes 2nd meiotic division : mitosis..423 ovum spermfertilization(X.. )zygote46 chromosome( (

non dis junction teratogenfiberscentriole teratogendrugviral teratogen 2 24 chromosome 22 chromosome

So, 2 ova formed 1stcontain 22 chrosomes & the 2ndcontain 24 chromosomes zygote:if sperm ( contain 23 chromosomes ) fertilize 1stovum ( that contain 22 ch. ) so, zygote = 45 ch zygote45chromosomes2chromosome onosomy21

So called , monosomy 21

If 13 calledmonosomy 13 etc Ovum chromosome(21) sperm1..monosomy 21

if sperm ( contain 23 chromosomes ) fertilize 2ndovum ( that contain 24 ch. ) so, zygote = 47 cspermovum 2 chromosome(21) 321..1 2 So, called trisomy 21 , trisomy 13 .etc.

non disjunction Monosomy or trisomy ..onosomyarly abortion.. urner syndrome

trisomy..21Down syndrome13trisomoy....... normalchromosomes.. ( old maternal age)

29


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09echanism

- Breakage chromosomes:Short arm that has 2 regions

Long arm that has 3 regions mechanism region..region short arm - Deletion means Broken part is deleted ( lost) .. geneticsdash.. " "genetics chromosome99 P 2 - deletionregionshort armchromosome

5 P - deletionshort armchromosome5.. 21 Q - deletionLong arm 21)anti mongolism) ..4 P -deletionshort arm4 transloacation : paired chromosomeanother paired( acrometacentric) Called translocation short arm

(short.. ) t(t small) short armchromosome1020..( ..)

tp (10 - 20 )means translocation of short arm between 10 & 20 chromosome 1020(2010) 2 long arms2 short arms..tp ( 10 - 20 ) + t Q ( 10 - 20 ) 2balanced translocation carrier balanced translocation carrier ..2 2 acrocenteric chromosome(short arms)

,, short arm


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( ... )Long armlong arm ..45..functionally46

Called balanced translocation carrier generations Inversion :

-....Called inversion geneticsin " ( IN SMALL LETTERS )"- ring chromosome :

-chromosomeshort armlong arm.. ( - )Called ring chromosome..karyotyping

- ISo- chromosome formation : 1st meiotic division.... 232ndmeiosismitosischromosomes..fiberschromatid ..2

chromatidcentromerechromatid (()) iso chromosome..fibers short armLong arm..

chromatid ..short armshort armLong armlong (2 short( centromere

-regionsshort Mirror shape).. ) iso chromosome fertilizationzygote:With 3 short arms + 1 long arm

3 short arms 1 long arm

- Or With 3 long arms + 1 short arm iso chromosome iis


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Classification of chromosomal aberrationNumerical :

A - May defect in1 paired chromosome-..called an euploidy

- trisomyMonosomy& both are Due to non disjunction

autosomal trisomy 21 ) Down $ ( , trisomy 13 .etc

sex chromosomes :

X chromosome 3 X super female

may XXYklienfilter syndromeY chromosome XYYsuper male

-monosomyturner syndromeB - All paires of chromosomes

:Called polyploidy-triploidy :

-ovum 2 spermsCalled triploidyfertilization369 chromosomesas in vesicular mole

Early abortion

tetraploidy : zygote2.. mitosis chromosomes2 chromatid..chromatidchromosome

-Failure of separation of cell(..)

4called tetraploidy

Structural as :Deletion

Ring chromosome

Translocation

Isochromosome

-uplication chromosomeregion13(13)


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,,breakage2 identical chromosomes.. (region1 - 2 - 2 - 3 1 - 3) translocation

Mosaic :

-structuralNumerical..called mosaic Down syndrome-Down..

-Down3 of chromosome 21Which is acrocentric chromosome And also, short chromosomeshort arm short arm()

Types ( cytogenic type ) =mechanism

Non disjunction ( Very common )

- failure of separation of chromosome 21 .. So, zygote contain 2 of 21

(46.. )zygote47 -95 % of Down is non disjunction type .

incidence with age of mother (..35) % Down0.536 3

So, 39 years1 % , 43 years2 % & 45 years0 %(Menopause ) Translocation

Represents 4 % of Down stem celltestesovary 21..13short arm2113Long arm21..TranslocatedLong arm13 Balanced translocation carrier45 chromosome

2 gametes(by 1stmeiotic devision)Long arm21long13.. 13 21


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.... 46..2 of 13 + 2 of 21 + 42 others-2113:

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 )

-..4542 others + 1 of 13 + 1 of 21 + 1 adh.So, give 2 cells .. 1stone contain 21 others + 1 of 13 + 1 of 21 = 23 chromosomes

& other cell contain 21 others + 1 adh. = 22 chromosomes -A1A2..:

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 212 of 13..stem cell 13 long arm21 long arm stem cell2 gametes 13 21Long arm21Long arm13:

42 others + 2 of 13 + 2 of 21..: 2113.. B1 & B2B1 = 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 cell2 of 212 of 13 long arm13Long arm13 long of 21

13 Long armLong212


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: 42 others + 2 of 13 + 2 of 21..: 1321.. C1 & C2C1 = 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

Other gametes( Ovum sperm) gametes ( (21(Sperm(testis13stem cells 45..Functionally 46)

-spermSS = 21 others + 1 of 13 + 1 of 21 = 21 + 1 + 1 = 23 chromsomes

.. .... (: )1 = 21 others + 1 of 13 + 1 of 21 = 21+1+1=23 chromosomes

2 = 21 others + 1 adheised ( 13&21 ) = 21+1 = 22 chromosomes

= 21 others + 1 of 13 = 21+1 = 22 chromosomes

2 = 21 others + 1 of 21 + 1 adhesied ( 13&21 ) = 21+1+1= 23 chromosomes ..B2 = 21 others + 2 of 21 + 1 of 13

= 21 others + 1 of 21 = 21+1 = 22 chromosomes

2 = 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

- fertilizationzygote( :zygouteZ)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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.. 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 : 213221..2(Balanced translocation carrier.. )zygote 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 - 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 :

-213321trisomy 21(Down $)(Down contain 46 chromosome But functionally 47 )

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 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 :-221313trisomy 13

(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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) 45functionally46non 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 alanced translocation carrier(1ther chromosome

:25 % Down

25 % balanced translocation carrier

25 % normal

- 25 % trisomy of the chromosome

(monosomy1321early abortion)-Down25%.. 33.. %trisomy

: Other trisomy25 % 33 % survey balanced translocation carrier(21 adhese to other chromosome) Down10 - 15 %(As actual risk incidence) 25 %-Downanomalies (Early abortion)

balanced translocation carrier -survey2 - 5 % 25 % motility sperm Downextra chromosome..

sperm fertilization ""


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21..212 long arm ..2 of 21..gametes 21fertilizationsperm gametes 21..Monosomy 21() gamete 2 of 21..Trisomy of 21Down alanced )abortion..100 %( ..Down

translocation ( )sperm 3 of 21.. (sperm 21 monosomy of 21abortion..

History of repeated abortion May balanced translocation of husband Mosaic mongol 1 % : Normaltrisomy 21..

10,,, balanced translocation carrier.. .. ) translocation(2

No abnormality could be detected

General clinical presentation of any autosomal chrosomal disordersMental retardation

degreesidiot() sphincter control Growth retardation

- ..history All brain sized microcephaly

All in head circumference

- May multiple congenital anomalies anomalyMultiple.. ..disorderstress Eye

May micro ophthalmia


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Cataract or glaucoma

May lip anomaly

Cleft lip , Cleft palate Or both

Congenital heart disease

In Down common AV canal Trisomy 13 left to right shunt ,,, midline defect

Hernias

Umblical or inguinal HypotoniaGenital anomalies

May as bilateral un descending testis called cryptochidism Unilateral un descending testisLimb anomalies

Poly dactyl ( )Rocker bottom heel

foot.. (heel.. )complete dorsiflexioncomplete dorsiflexion

(anomalies..)Specific manifestations in Down syndromeclinical pictures

Associated anomaliesCongenital heart disease

GIT anomalies

Pyloric stenosis

May dudenal atresia May congenital megacolon

Renal anomalies : as

Polycystic kidney

Or Ptosed kidney ( in pelvis )

Or horse shoe kidneyAnomalies in thyroid

May associated with autoimmune thyroiditis ( Hashimoto's )

Causes of death in DownAssociated anomalies as :


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Renal failure

Congestive heart failure

Associated repeated infection severe hypotonia.. (acrobatic sign) ()herniaPtosed liver and spleenWeak respiratory muscles

,,,,,Causes of repeated infections in Down syndrome

chest infectionHypotonia

Shallow respiratory movement + weak cough reflex

) Congenital heart disease

Lung congestion and plethora

) Associated T cells dysfunction

So, humoral and cell mediated immunity

N.B. Incidence of leukemia

normal20& Leukemia cause immunity

) so, Leukemia incidence of infections

Mental retardation .. - Leukemia Un explained sudden death.

linical picturesand- sedni crease , complete simian crease or incomplete Simian crease : 3 main crease:

1- longitudinal crease

2- proximal horizontal crease handthumb(2lateral)3-medial sideDistal horizontal crease

own proximal horizontal..called sedni crease


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distalproximalCalled complete simian crease another crease() Normal complete simian crease partial flexion Called incomplete Simian crease- brachy dactyl - rudimentary middle phalanx of little finger .

-Little finger2 crease onlyrudimentary middle phalanxincline dactyl

-Called inclino dactylInvestigations

In all genetics Karyotyping

KaryotypingDownclinical diagnosis cytogenic type of Down 47(321)non disjunction 46translocation 4647mosaic patternChest X ray ,,,, X ray chest and heartDown congenital heart disease( )

chest infectionPneumonia enlarged mediastinal lymph nodes(If associated with leukemia)..May associated Hashimoto's thyroiditis...retro sternal goiter

Investigations for Leukemia leukemia..CBC6..bone marrow examinationBM examination for early detection of leukemia

Thyroid function thyroidSonar on abdomen

ECG and ECHO heartBarium study

- IQ for associated MR


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TreatmentNo thing .. Only special care and supportive treatment

What about future pregnancy ???,,, Karyotyping

- 47(non disjunction.. ) Down(35)Down..rophoblastic biopsy 6 - 8)amniocentesis(.. ) Downabortion (induced abortion12

)trophbalst6 - 8..abortion abortion 1314..mniocentesis

contraceptive trohpobalastic

karyotyping 46extra chromosome()21other..Non disjunction2121..tubal ligation()

Trisomy 13NBamniotic fluidkaryotyping karyotyping133,,,

Enumerate autosomal chromosomal aberration and discuss one of them ??Most common DownTypes

As Down with same risk factors ( as Down ) Clinical pictures

Mental retardation

Growth retardation

Microcephaly


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Multiple congenital anomalies general ..3- All defects are Midline defects

Eye oMay single eyecalled cyclopia

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

organs palpationGenital defects

Un descending testis+hypospedius?????? polydactylyCapillary hemangioma

InvestigationsKaryotyping + investigate anomalies

TreatmentAs Down Leukemia

Trisomy 18 ( Edward syndrome )Types

As Down

Clinically+Specific manifestations

Hyper tonia (CP(cerebral palsy


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In trisomoy 13 may hypo , may hyper

Down hypo

Prominent occiput

Ears Down..Low set ears.. Lateral angle of the eye.. ragus earDown(chromosomal)

-18Low set ear+malformation- Hands Clinched fist Hypertonia ringmiddlepalm Overlapped Rocker bottom heel

Investigations and treatmentAs Down

cri-du-chat-syndrome = 5 P -Deletion of short arm of 5th chromosome

Called cri-du-chat-syndrome

Clinical Manifestations +3Round face Marked hypertelorism Cat like cry

due to laryngeal hypoplasia

InvestigationsKaryotyping

TreatmentSupportive treatment

anti mongolism = 21 Q -Deletion of long arm of chromosome 21 .. Called anti mongolism

Clinically +Hypertonia

downward slanting of the eye :


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- In Down low set ear ( ) Upward slanting of the eyelateral anglemedial angle

-..Medial anglelateral angle(downward slanting of the eye) Prominent nasal bridge

Down- Large ear

own InvestigationsKaryotyping

TreatmentSupportive

Sex chromosomal aberrationturner syndrome embryomale..Y chromosome femaleY chromosome.. no formation of male genital system

turner syndrome..only one X chromosome XXSo, no Barr body( Only one short arm and one long arm )

Criteria :) Female as there is no Y chromosome

) Short stature sex chromosome(4)2 on each X if female Or 2 on X and 2 on Y if male2..2

) Abnormal somatic features

Webbing of the neck fold of skin around the neck .

Wide spaced nipple :


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Nippleat mid clavicular lineout side mid clavicular lineSo, wide spaced n

Congenital heart disease :

coarctation of Aorta- wide carrying angle :

-forearmradius and ulna..Ulnaradius full supination..trunkCarrying angle radiusSo, wide carrying angle pronation..elbow

genreralized non biting odema at birth

- Intra uterinesonar generalized edema..non biting..lymphatic-lymphatic hypoplasia

triangular face

-triangular facechinforeheadNo menstruation No 2ry sexual character

-13-15 sonarovary..fibrotic ovaryinfertileturner

deletion of short arm of one of X chromosome( 46 XX P - )- buccal smearBarr body short armX deleted(46 XX P -)

deletion of short arm of one of X chromosome-turnerovarian function

- normal menstruation , Normal 2ry sexual character & normal menopause

-Lyon X long armBarrfunction of the ovary(


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deletion of long arm ( 46 XX Q - )

46 XX Q -..deletion of long arm..female() (fibrotic ovary(

no menstruation , no 2ry sexual character

ry infertilityurner

mosaic turner : X...mosaic turner()

enopause..5 ,,, turner mosaic XX P -(Deletion of short arm only)turner

InvestigationsBuccal smear no Barr body

estrogen as fibrotic ovaryFSH & LH ( pituitary gonadotrophins ) ( no ve feedback )

Sonar fibrotic ovary

Diagnostic karyotyping

Treatmentfor short stature give growth hormone

Hormonal replacement therapy .. for 2ry sexual features

female (but still infertile) clinical features of Down on data show311:34

skull circumference microcephaly

Fine hair


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Brachycephaly ( occiput flat )

- Eye :

depressed nasal bridgeand medial epicanthus So, apparent convergent squint.

upward slanting of the eye ( medial angle(Down..Lateral angleMicro ophthalmia

Iris brush field iris Iris with line of demarcation Scrotal tonguemeans prominent rogue on the tongue

( tongueScrotum)micrognathia().... .. sucklingtongue

hypertrophy of papillae of tonguefrom prolonged suckling

In hands

Simian crease

Inclino dactyl

Brachydactyl wide space between big toe and other toes:

..wide space between big toe and other toes On sole :

deep grove opposite space between big and other toes

Acrobatic sign due to severe hypotonia

(NBDown1886)Trisomy 13 also, on data show

Marked micro ophthamia May single eye

Nonann syndrome -turner-196321


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P a g e |35 " ":,, :"" " 2012

,,, ..femaleShort stature, webbing of neck + skeletal deformity :turner syndrome : .. turner

mosaic turner- 46 XX P ( ( gametes1st meiotic.. 23gameteX() 2nd meiotic division mitosis fibers

fibers ..short armLong arm 2 gametesshortLongshortshort armlongLong arm

( (Xfertilizationgametes ..turner phenotype1 short arm 2 short arms2 long arms

if gamete with 2 short arm fertilized by normal gamete ( 1 short and 1 long ) ..3 short arm + 1 long 2short 43 short..6So, tall female Long arm..

Degenerated ovaryno 2ry sexual characters (Fibrotic ovary )

or gamete with 2 long arms fertilized by nomral gamete ( normal gamete contain 1 long + 1 short )

So, net result 1 short + 3 long

webbingcoarctationskeletal deformity


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P a g e |36 " ":,, :"" " 2012

3 longSo, appearance of 2ry sexual character+() menopause(Long fertility age)degenerationovary..ovary3support..long):turnerturner

Due to iso chromosome of the long arm of the X chromosome( )turner..featuresturner

Called Nonann syndrome Nonannturnernonannurner

autosomal recessive gene defchromosomal disorder

( 1 X, 1 short arm or iso chromosome

long arm )

Etiology

male or femaleMust be femaleSex

variable degrees of MRnormalMentalitity

congenital pulmonary stenosCoarctation of the AortaCongenital heart disease

fertileClassic type infertileFertility

normalAbnormalKaryotyping NonannMR :mild MR..severe MR

illegal pregnancy

Intra uterine criteria of turnerGeneralized edema

-heart failure-edema Hydrocephalus

After delivery Triangular face

Coarctation of AortaWebbing in neck

Dorsum of hands and footsnon pitting edema

N.B.95 % of turnermonosomy5 %


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P a g e |37 " ":,, :"" " 2012

Klinefelter syndrome2 X + 1 Y So, 47 XXY

Male as there is Y (6)2X2YSo here , tall stature

has2 X so,More ovarian genes Cause atrophy of testis ( degeneration of gonadal cells )

(ovarian genelong armX..short)No somatic deformities ..

. No 2ry sexuall characters :

testosterone Other sex .. ) .. ( )

fat with female distribution of fat musclefatmusclefat..Klinlfelterand female distribution of fat ( buttocks & breast (gynecomastia ) )

Feminine behaviour 30 %Homosexual(same sex)Investigations

Buccal smear Barr body

testosterone level

FSH & LH

Fibrotic testis (ovary)

Karyotyping 47 XXY 47 XXYcalssic..48 XXXY(2X) 47 XXYmentalitynormal()But only emotionally affected ..behaviourfemale femaleXY neuronal cellsheart ) :


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P a g e |38 " ":,, :"" " 2012

brain decesions dominate heart decesions.. ..( )

.. .. ).. 1005(.. ) :..female .. chromosome XMental retardationturnerMR

(x..)

Enumerate chromosomal disorders that cause MR ??

- all autosomal

sex chromosomal disorders...turner- ....turner..female

attitudemale(X.. (..uperfemale-

KlinfelterMosaicTreatment testosteronesomatic features

Superfemale , supermale & fragile X -n born eror 0 2

henyl kentonuria and galactosemia


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genetics - dr abo-elasrar - by el azhar medical students 2012

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