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Chapter4Chapter4Chromosome DiseaseChromosome Disease

Chromosome Disease

Clinical featureThe general features in autosome abnormalitiesThe general features in autosome abnormalitiesare a triad of growth retardation, mentalretardation and specific somatic abnormalitiesretardation, and specific somatic abnormalities.

Change of sex chromosome also have theChange of sex chromosome also have theabnormalities and malformations of internal orexternal genital organsexternal genital organs.

Chromosome Disease in ClinicalDownDown SyndromeSyndrome (trisomy 21 syndrome)

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Erik Nichols and mother,Erik Nichols and mother,St P t b FLSt P t b FLSt. Petersburg, FLSt. Petersburg, FL

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Erik Nichols, 21, and his sister, 17Erik Nichols, 21, and his sister, 17--yearyear--old Lindsey,old Lindsey,on their graduation from high school.on their graduation from high school.

(S i P b FL)(S i P b FL)(Saint Petersburg, FL)(Saint Petersburg, FL)

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Chromosome Disease in Clinical

1 in 600 ~ 800 newbornsDownDown SyndromeSyndrome (trisomy 21 syndrome)

CharacteristicsCharacteristicsG th t d ti

1 in 600 800 newborns

o Growth retardationo Varying degrees of mental

retardationo Flattened faceo Upward slanting of the eyes

with epicanthal foldswith epicanthal folds

Chromosome Disease in Clinical

1 Trisomy 95% 47 XX(XY) ＋21

DownDown SyndromeSyndrome (trisomy 21 syndrome)

1. Trisomy —— 95%, 47, XX(XY), ＋21Caused by non-disjunction of chromosome

21, correlated with age of mother.

Chromosome Disease in Clinical

1 Trisomy 95% 47 XX(XY) ＋21

DownDown SyndromeSyndrome (trisomy 21 syndrome)

2. Mosaic —— 2% ~ 4%, 46/471. Trisomy —— 95%, 47, XX(XY), ＋21

Karyotype of affected：

3. Unbalance translocationKaryotype of affected：

46, XX(XY), －14, ＋t(14q21q)Karyotype of balance carrierKaryotype of balance carrier：

45, XX(XY), －14, －21, ＋t (14q21q)

Chromosome Disease in Clinical

1 in 4000 ~ 5000 newborns

EdwardsEdwards SyndromeSyndrome (trisomy 18 syndrome)

1 in 4000 5000 newbornsCharacteristicsCharacteristics

o Growth retardationo Mental retardationo Congenital heart diseaseo Rocker-bottom feeto Rocker-bottom feeto fixed flexion deformity of the

fifingers

Chromosome Disease in Clinical

1 in 4000 ~ 5000 newborns

EdwardsEdwards SyndromeSyndrome (trisomy 18 syndrome)

1 in 4000 5000 newborns

Chromosome Disease in Clinical

1 in 5000 ~ 7000 newborns

PatauPatau SyndromeSyndrome (trisomy 13 syndrome)

1 in 5000 7000 newbornsCharacteristicsCharacteristics

o Varying degrees of mentalretardation

o Cleft lip & Cleft palateo Polydactyly (postaxial)o Polydactyly (postaxial)o Equinovarus

Chromosome Disease in Clinical

1 in 50000 newborns

55pp－－ SyndromeSyndrome (Cat Cry syndrome)

1 in 50000 newbornsCharacteristicsCharacteristics

oo Round,Round, moonmoon--shapedshaped facefaceoo “Cry“Cry ofof thethe cat”cat”oo VaryingVarying degreesdegrees ofof mentalmental

retardationretardationretardationretardationoo LowLow setset earsears

（（ ））46, XX46, XX（（XYXY））, del ( 5 ) ( p15 ), del ( 5 ) ( p15 )

Chromosome Disease in ClinicalTurnerTurner SyndromeSyndrome (45, X)

1 in 2500 liveborn females1 in 2500 liveborn femalesCharacteristicsCharacteristics

oo Short stature & Short stature & Webbed neckWebbed neckoo Ovarian dysgenesis,Ovarian dysgenesis, primary primary

amenorrhea, amenorrhea, infertilityinfertilityoo Absence of secondary sex Absence of secondary sex

characteristicscharacteristicsoo Underdeveloped breasts; Underdeveloped breasts;

wide nippleswide nipples

Turner’s SyndromeTurner’s Syndrome

Described in 1938 by Henry TurnerDescribed in 1938 by Henry TurnerCause isolated in 1960 (loss of one/part of one sex chromosome)Cause isolated in 1960 (loss of one/part of one sex chromosome)

Background:Background:

••Short Stature (mean height < 5 feet)Short Stature (mean height < 5 feet)

9 ( /p x )9 ( /p x )

Physical Symptoms:Physical Symptoms:Short Stature (mean height < 5 feet)Short Stature (mean height < 5 feet)

••Failure to develop secondary sex characteristicsFailure to develop secondary sex characteristics••Maldeveloped Ovaries (infertility; high risk of ovarian cancer)Maldeveloped Ovaries (infertility; high risk of ovarian cancer)••Variety of medical problems: cardiovascular, kidney, pancreas,Variety of medical problems: cardiovascular, kidney, pancreas,Variety of medical problems: cardiovascular, kidney, pancreas,Variety of medical problems: cardiovascular, kidney, pancreas,

skeletal, thyroid: MARKED VARIABLE EXPRESSIVITYskeletal, thyroid: MARKED VARIABLE EXPRESSIVITY••Minor physical anomalies: webbed neck, low set ears, puffy handsMinor physical anomalies: webbed neck, low set ears, puffy hands

and feet: MARKED VARIABLE EXPRESSIVITYand feet: MARKED VARIABLE EXPRESSIVITY

••Normal intelligenceNormal intelligenceBehavioral Symptoms:Behavioral Symptoms:

gg••Normal personality (problems of selfNormal personality (problems of self--esteem and body image thatesteem and body image that

may be associated with physical anomalies)may be associated with physical anomalies)••Lowered spatialLowered spatial--visualization and quantitative reasoningvisualization and quantitative reasoning••? Higher stereotypical feminine interests? Higher stereotypical feminine interests

Chromosome Disease in ClinicalTrisomy X syndrome (47, XXX)

1 in 1000 liveborn females1 in 1000 liveborn females1 in 250 psychopath of females

Two of the three X chromosomes are inactivated.

Chromosome Disease in Clinical

1 in 800 males

Klinefelter syndrome (47, XXY)

1 in 800 males1 in 100 mentally retarded males1 in 10 infertile maleso Tall with disproportionately long

1 in 10 infertile males

arms/legso Poorly developed secondary sex

characteristicso Testicular dysgenesiso Testicular dysgenesis

Chromosome Disease in Clinical

1 in 750 ~ 1500 males

XYY syndrome (47, XXY)

1 in 750 1500 males1 in 30 male prison populationso Tall stature＞180 cm: 1/200/＞190 cm: 1/30＞200 cm: 1/10

o Predisposition to violent, criminalbehaviorbehavior

Chromosome Disease in Clinical

1 in 1250 males

Fragile X chromosome syndrome (Fra X)

1 in 1250 malesCharacteristicsCharacteristics

o Show mild to severe mental retardation

o Large, protruding earso Enlarged testeso Enlarged testeso Narrow face with a prominent chin

B h i l blo Behavioral problems