cytogenetic disorder

Cytogenetic disorders: 

Cytogenetic disorders Dr. Arjun Singh M.D. Pathology Associate Professor Index medical college hospital and Research Center, Indore, India

objectives: 

objectives Types of mutations Autosomal disorder Down syndrome Edward syndrome Patau syndrome Sex chromosome disorder Turner syndrome Klinfelter syndrome

Cytogenetic disorder: 

Cytogenetic disorder Mutation that form an abnormal number of chromosome or alteration in the structure of one or more chromosome Normal male 46,XY and female 46,XX Euploid :- exact multiple of haploid number Anuploid :- not an exact multiple of 23 Causes are nondisjunction or anaphase lag Mitotic error in early development responsible for two or more population of cells in same individual called as mosaicism

Type of mutation: 

Type of mutation Translocations Balanced reciprocal Centric fusion or robertsonian Isochromosomes Deletions Inversions Paracentric Pericentric Ring chromosomes

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Balanced reciprocal Centric fusion Robertsonian Translocations Fragment Deletions 46,XX,del(16)(p11.2p13.1) 46,XX,t(2;5)(q31;p14)

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Paracentric Inversions Fragment Ring chromosomes Pericentric 46,XY,r(14)

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Isochromosome 46,XX,i(X)(q10)

Cytogenetic disorders involving autosomes: 

Cytogenetic disorders involving autosomes Trisomy 21 Down syndrome Trisomy 18 Edwards syndrome Trisomy 13 Patau syndrome

Trisomy 21 Down syndrome: 

Trisomy 21 Down syndrome Most common chromosomal disorder Major causes of mental retardation 95% are classical type Trisomy 21 with extra X chromosome from maternal origin 47,XX,+21 Common in Maternal age below 20 year and above 45 year 4% are translocation type 46,XX,der(14;21)(q10;q10),+21 1% are Mosaic type 46,XX/47,XX,+21

Trisomy 21 Down syndrome: 

Trisomy 21 Down syndrome Diagnostic clinical features are facial profile , oblique palpebral fissures and epicanthic folds 80% cases have IQ below 25 to 50 40% cases are having congenital heart disease ASD , VSD etc 10 to 20 fold increased risk or leukemia Nearly all at 45 year age develop neuropathic changes i.e. Alzheimer disease Predispose to infections i.e. lung

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Trisomy 21(Down syndrome) Extra 21 chromosome

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Trisomy 21(Down syndrome) Phenotype presentation

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Trisomy 21(Down syndrome) Clinical presentation Epicanthal fold

Trisomy 18 Edwards syndrome: 

Trisomy 18 Edwards syndrome Incidence 1 in 8000 live birth Trisomy 18 type 47,XX,+18 Mosaic type 46,XX/47,XX,+18

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Trisomy 18(Edwards syndrome) Extra 18 chromosome

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Trisomy 18(Edwards syndrome) Phenotype presentation

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Trisomy 18(Edwards syndrome) Clinical presentation Micrognathia Prominent occiput

Trisomy 13 Patau syndrome: 

Trisomy 13 Patau syndrome Incidence 1 in 15,000 live birth Karyotypes Trisomy 13 type 47,XX,+13 Translocation type 46,XX,+13,der(13;14)(q10;10) Mosaic type 46,XX/47,XX,+13

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Trisomy 13(Patau syndrome) Extra 13 chromosome

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Trisomy 13(Patau syndrome) Phenotype presentation

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Trisomy 13(Patau syndrome) Clinical presentation Polydactyly-6 finger Cleft lip and palate

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Trisomy 13(Patau syndrome) Clinical presentation Cleft lip and palate

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Trisomy 13(Patau syndrome) Clinical presentation Rocker bottom feet

Cytogenetic disorders involving sex chromosome : 

Cytogenetic disorders involving sex chromosome Lyon hypothesis :- X inactivation One X is genetically active Other X is inactive Inactivation occur randomly in all blastocyst on 16 th day of embryonic life Inactivation persist in all cell derived from each precursor cell Xist gene → non coding RNA → coat X chromosome → result gene silencing → by DNA methylation Xist remains off in active X chromosome Y chromosome (Sry; Sex determining region) Y , and male specific, Y gene located on distal short arm

Cytogenetic disorders involving sex chromosome : 

Cytogenetic disorders involving sex chromosome Features are common in all sex chromosome disorder Causes subtle, chronic problems relating to sexual development and fertility Difficult to diagnosed at birth, many are first recognized at puberty Higher the number of X chromosome in both male and female, greater the mental retardation

Turner syndrome: 

Turner syndrome Incidence 1 in 3000 live birth female Classical type 57% missing of one X chromosome 45,X Defective second X 14% Deletion of small arm resulting formation of isochromosome of long arm 46,X,i(X)(q10) Deletion of portion of both short and long arm resulting formation of ring chromosome 46,X,r(X) Deletion of portions of the short or long arm 46,X,del( Xq ) or 46,X,del( Xp ) Mosaic type (1) 45,X/46,XX (2) 45,X/46,XY (3) 45,X/47,XXX (4) 45,X/46,X,i(X)(q10)

Turner syndrome: 

Turner syndrome Result from complete or partial monosomy of X chromosome and is characterized primarily by hypogonadism in phenotypic female Swelling of the nap of neck, webbing neck Congenital heart disease i.e. coarctation of aorta and bicuspid aortic valve Failure to develop female secondary sex character Primary amenorrhea, streak ovary, short stature

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X CHROMOSOME q p Phenotype Gene (condidate) SHOX EIF1AX, ZFX,USP9X, DBX, UTX, SMCX RPS4X Stature, skeltal anomalies, neurocognitive deficit Stature, gonadal failure, Minor physical features Viability Gonadal failure

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Monosomy X(Turner syndrome) Isochromosome Xq;resulting monosomy of Xp

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Monosomy X(Turner syndrome) Single X chromosome

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Monosomy X(Turner syndrome) Phenotype presentation

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Monosomy X(Turner syndrome) clinical presentation Webbed neck Multiple pigmented nevi Wide spaced nipple Shield chest

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Monosomy X(Turner syndrome) Turner syndrome Normal Short 4 th Metacarpal

Klinefelter syndrome : 

Klinefelter syndrome Male hypogonadism that occur when there are two or more X chromosome and one or more Y chromosome Incidence 1 in 500 live birth male Classical type 47,XXY (82%) Mosaic type 46,XY/47,XXY Rare type 48,XXXY, 49,XXXXY

Klinefelter syndrome : 

Klinefelter syndrome Phenotype Long legs , small atrophic testis with small penis Lack of secondary male features , increase FSH , reduced testosterone Mental retardation uncommon Associated with breast carcinoma , extra gonadal germ cell tumors , SLE (Autoimmune disorder)

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Extra X chromosome(Klinefelter syndrome) An extra X chromosome

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Extra X chromosome(Klinefelter syndrome) clinical presentation Small Penis Atrophic testis Gynaecomastia Long leg

summary: 

summary Types of mutations Autosomal disorder Down syndrome Edward syndrome Patau syndrome Sex chromosome disorder Turner syndrome Klinfelter syndrome

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