Gr

ossst
ruct
uralabnor
mal
it
iesi
nthechr
omosomes

Thechr omosomesar emadeupofDNAandot herpr otei ncompl exesandcont ain

mostoft hegenet icinformat iont hatpassedf rom onegener ati
ont ot henext .Theyar e
visual izednor mallyt hr
ought hemi croscopeonl ywhent heyar einacont ractedst ateas
theygot hr oughcel ldivision.
Chr omosomesar ear r
angedbysi zei npai rs,thel argestbei ngchr omosome 1andt he
smal l
esti schr omosome 22 and t hen sexchr omosomesX & Y.t he posi tion of
cent romer ei nr egar dtot hechr omosomear msi sant herdi stingui
shi ngf eatureofeach
chr omosome.Theshor tar m oft hechr omosomei sr eferredt oasp( from pet it
)andt he
l
ongar m asq.
Kar yot ypi ng:r eferst osy stemi car rangementf rom phot ogr aphorbyacomput erof
prev iousl yst ainedandbandedchr omosomesofasi nglecel lbypai r
s.Thecel l
sar e
cultur ed,ar rest edi nmi t
osisdur ingmet aphaseandt henf ixedandst ained.I ff i
ner
det ailsar enecessar ypr ophasechr omosomesar el ongerandl esscondensed.They
show 600- 1200 bandscompar ed wi th met aphasechr omosomes400- 600 bands.
Ty psin- Giemsast aininggi vesGbandi ng–Qui nacrinegi vetheQ(f luorescent)bandi ng.
Speci alstai nsar eusedt odemonst rat ecent romer s.Thebandi ngpat ter
ni suni quef or
i
ndi v i
dual chr omosomesandi s( almost )ident i
cal i
nal lindividuals
Chr omosomeshav epol ymor phi smst hatdifferamongi ndividualswi thoutaf fecting
phenot ypi
cl ike: arm oft heYchr omosomeandRegi onsoft heshor tar mssat ell
iteson
13, 14, 15, 21, and22.
FISH( fluor escenti nsi t
uhy bri
dizat ion)usesaf l
uor escentpr obet oanneal to
speci f i
car easoft hechr omosomes.
 Chr omosomeanal ysiscanbedoneonanyt i
ssuey oucangr ow( mostcommon
aret heper ipheral bloodandbonemar r
ow)

Nomencl
atureofchr omosomes:#chr omosomes,sexchr omosomes, +any
abnor
mali
ti
es
 Normalf emale: 46, XX
 Normalmal e: 46,XY
 Changesi nchr.#:
o Trisomy : 47,XY, +21
o Monosomy : 45,XO–Tur ner
’s(monosomyi sgeneral
lyonlyseenfor
theXchr omosomesbecauseamonosomyi nt he
autosomesusual l
yisalethaldisor
der)
 Deleti
onsandaddi t
ions:
o 46, XX,18p- (del
eti
onofshor tarm ofchr.18)
o 46, XY,3q+ (addi
tionofextr
amat eri
altolongar m ofchr.3)
 Translocat
ions:
o 46, XX,t(3;
4)(
p13;q20) ( f
emalewithtr
anslocationofchr.3and4wi t
h
1
 breakpointsinshortandl ongar msr especti
vely)
o 46, XX, t(3;
4) (translocati
onwi t
houtbr eakpointsspeci
fi
ed)
o 45, XX, t
(13q/14q) ( i
ndicat i
ngaf emalecar r
ieroftranslocat
ionbetween
thel ongar msofchro.13and14)
Sot ranslocat i
onmaybebal anced( personwi t
hnor mal amount sofgeneti
c
materialandanor malphenotype)orunbal anced( personwi t
hmi ssingor
addit
ional mat eri
alandanabnor malphenot ype)
 Mosai cs:( anycombi nati
onoft heabov ewheret hereismor ethanonecell
l
i
ne)
o 45, XO/ 46, XY
o 46, XX/ 47,XX, +21

2
3
Ty
pesofst
ruct
ural
abnor
mal
i
ties

4
5
I
nci
denceofChromosomeDi sor
der
sineachgroup:
 SpontaneousAbor ti
on50% (
Thesingl
emostcommonchromosomal
abnor
mal i
ty amongabor t
usesi
sTur ner
’ssy
ndr
ome-18%abor
tuses,
0.6%
l
ivebi
rths)
 Neonat aldeaths-50%
 Bi r
thdefects-70%

Genet
icDi
agnosis:
Featuresofdi
sorder
Fami l
yhist
ory
Thinki
ngandr esear
ch
Tests

I
ndi
cati
onsf orcy t
ogeneticanal ysis:
1.Confirmat ionofasuspect edclassicalchr omosomal sy
ndr ome
2.Mul t
iplecongenital anomal ies/
ment alretardati
onsy ndromes
3.Coupl eswi th2+spont aneousabor ti
ons/ undeterminedinferti
li
ty
4.Allabor tusesandmal formedst i
ll
borns/ allphenoty
picall
ynor mal st
il
lbornsof
undet erminedetiology
5.Femal eswi t
hpropor ti
onallyshortstatureofunknownet iol
ogy( speci
ficall
y,
checki ngf orTur
ner ’
ssy ndrome)
6.Pri
mar yamenor rhea/ secondaryamenor rheaofunknownet i
ology
7.Puber talfail
urei
nei thersex
8.Ambi guousgeni tali
a
9.Suspect edFr agi
leXsy ndrome

Cyt
ogeneti
cdi sorderscausethr
eet y
pesofpr obl
emsandt heymayalloccurint
he
af
fect
edper son:
1)Growt habnor malit
ies
2)Ment alretardati
on
3)Birt
hdef ect
sanddy smorphi
cf eat
ures
o Handsandear sar eof
tendy smorphi
cingenet
icabnormal
it
ies
o Al way scompar esuspectedabnormalit
ieswi
thparent
s’f
eatures-Itmayj
ust
beanor mal v
ari
antinthatfamil
y

6
 Tr
isomi
es
Downsyndr ome( DS)
 Affect s1i nev ery600- 800l i
vebirths
 Femal eswi t
hDownshav eear l
ymenopause,
butcanhav echi ldren
 Mal esar eusual l
yst er i
l
e.
 Theper cent ageofpr egnanciesresul t
ingin
DSgr owsexponent iall
ywhent hemot heri
s
overt heageof35.( Howev er,
mostDowns
syndr omechi l
dr enar ebor ntowomenunder
theageof35, sinceav astmaj ori
tyof
pregnanci esoccurundert hatage. )
 Classi calf eatur esi nclude:Ment al
retardat ion( 100%) ,congeni t
alhear tdefect
(50%)
Ot her sar e:
 Br achy cephal y
 Mi cr ocephal y
 Fl atf aci alpr ofile
 Shor tneckwi thexcessski natnape
 Smal lf aci alfeat ures
 Shor tfol dedov erear s
 Wi spyhai r
 Shor tnose
 Br ushf iel dspot s
 Shor t5t hf ingerwi thclinodactyl
y
 Si ngl et ransv er sepal marcr ease
 Wi degapbet ween1stand2ndt oeshy potoni
cit
y

 Shortpal
pebralfi
ssur
est
hatsl
antup(
ordowni
f
chi
ldhaslar
gej aw)

 CausesofDS
1.Trisomy21–account sfor95%ofindivi
dual
s
withDS
 Duet onondisjuncti
onintheova
I nci
dencei
ncreaseswi t
hmat er
nalage
oAge35-1i n200livebi
rt
hs
oAge40-1i n40liv
ebirt
hs
7
 oAge45-1i n15l i
vebirths
 Nondi sjunct ioncanoccuri neitherMei osi sIorI I(seepi cture)
2.Translocat ion:chr omosome21t ranslocat edonanot herchr omosome
especiallyanot heracr ocentri
cchr omosomese. g.13, 14, 15,21,22.
 Account sf or2- 4%ofi ndivi
dual swi thDS
 Pr ognosi si st hesamef orTr i
somy21pat i
ent s
 Thesei ndiv idual shav eone14/ 21t ranslocat i
onandt wonor mal chr.21's
andt hust heyexpr esst hesamephenot y picchar acteri
st i
csasi ndivi
duals
withtrisomy21
 Denov ot ransl ocat i
onoccur sabout50%oft het ime( thisisduet o
breakageandr ecombi nati
onoft hechr omosomes–t estthepar ents,they
willbenor mal )
 Theot her50%i sinher it
ed-oneoft hepar ent scarri
esat ransl
ocat edchr .
21andanor mal chr .21
o Af ather ’
sr iskofpr oducingachi ldwi thanunbal ancedkar yotypeis5%,
butmot her ’sr i
ski s10-15%
o Ex. Fat her
Mot her
1414/ 2121 141421
21
(Balancedt ranslocation) (Normal )
Nor mal offspr ing 14142121 (2
14’s,221’ s)

8
 Bal
ancedtransl
ocation
(Normalphenotype) 1414/
2121 (
214’
s,2
21’
s)
Unbal
ancedtranslocat
ion
(Downsyndrome) 1414/
212121 (
214’s,
3
21’
s)

3.Mosaici
sm
 Nondi sj
uncti
onoccur saft
erfert
il
izat
ioninsomati
ccel
lsveryearl
yin
embr yoni
cdev elopment
I ndiv
idualshavenor mal chromosomesi nacert
ain%ofthetheircell
sand
DSi ntheremainingcel l
s
 Tendt ohavesl i
ght l
yhigherIQsandar esomewhathi
gherfuncti
oningthan
tri
somy21DSpat ients

9
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