Chromosome disorders (2)

Weiying Jiang Department of Medical Department

P261

Chromosome abnormality

Numerical abnormality

Structural abnormality

Aneuploidy

Polyploidy

translocation

deletion

insertion

inversion

rings

isochromosome

At least 20,000

Diploidy 46 chromosomes

Numerical abnormality

Aneuploid: One or a few chromosomes above or below the normal chromosome number.

Polyploidy: More than two sets of chromosomes per nucleus.

23 chromosomes = one set of chromosomes

Incidence of chromosome abnormalities 10% of all spermatozoa 25% of mature oocytes

Between 15% and 20% of all recognized pregnancies end in spontaneous miscarriage

Approximately, 50% of spontaneous miscarriage are a chromosome abnormality

chromosome abnormality in spontaneous abortions

Abnormality Incidence (%)Trisommy 13 2

Trisommy 16 15

Trisommy 18 3

Trisommy 21 5

Trisommy other 25

Monosomy X 20

Triploidy 15

Tetrepolidy 5

Other 10

Down’ syndrome

Down syndrome is characterized by well-defined and distinctive phenotypic features and natural history.

It is caused by trisomy of all or a critical portion of chromosome 21.

Down’ syndrome

Incidence:

1/1000 in UK

60% cases found prenatally

1/800 in USA

More than 350,000 people affected

Down’ syndromeDown’ syndrome

Clinic features of Down’ syndrome

New born period

Hypotonia SleepyExcess

nuchal skin

Clinic features of Down’ syndrome

Mental retardation Congenital malformations Characteristic facies Limbs

Clinic features of Down’ syndrome

Mental retardation：

Average IQ 40-45

Social skill are relatively well advanced

Average life span 50-60 years

Most affected adults develop Alzheimer

disease

Clinic features of Down’ syndrome

Congenital malformations (40-45%)

atrioventricular canal defect

Heart

ventricular septal defect

Patent ducts arteriosus

Clinic features of Down’ syndrome

Gastrointestinal tract

Ninety percent of all Down syndrome patients have a significant hearing loss, usually of the conductive type

Clinic features of Down’ syndrome

Estimates of the relative risk of Leukemia have ranged from 10 to 20 times higher than the normal population;

In particular, acute megakaryocytic leukemia occurs 200 to 400 times more frequently in the Down syndrome than in the chromosomally normal population.

Clinic features of Down’ syndrome

Characteristic facies

50% single palm crease

Gene map locus 21q22.3

Trisomy 21 (95%) : Patients have 3 free copies of chromosome 21.

Chr. Abnormality in Down’ syndrome

Translocation ( about 5% ): Patients have 1 copy to be translocated to another acrocentric chromosome, most often chromosome 14 or 21

mosaicism (2 to 4% ): Patients have a trisomic and a normal cell line

Trisomy 21 (95%)

Trisomy 21

Karyotype

47,XY, +21

47,XX, +21

Mechanism of Trisomy 21

Meiotic Non-disjunction

XX

X X

l l l l

Normal

Translocation Down’s Syndrome

Karyotype

14/21 translocation

46,XX(XY)., -14, +t (14q21q)

21/21 translocation

46,XX(XY)., -21, +t (21q21q)

Mechanism of Translocation Down’s Syndrome

14 21 14 14/21 21

CarrierNormal

14 21 14/21 14 14 2114/2114/21 21

Down’s syndrome Lethal

Mosaicism (2 to 4% ):

Mitotic Non-disjunction

Patau syndrome (Trisomy 13) 47,XX(XY),+13

Patau syndrome is a chromosomal condition that is associated with severe mental retardation and certain physical abnormalities.

Small eyes

An opening in the roof of the mouth (a cleft palate) and/or a cleft lip

An infant with trisomy 18 (Edwards syndrome), exhibiting characteristic facial features, short sternum, overlapping fingers with clenched fists, and a left-sided clubfoot.

Edwards syndrome (Trisomy 18)47,XX(XY),+18

Short stature

Turner syndrome (45,X)

Neck webbing

Intelligence is normal, but learning is difficult.

Neck webbing

Turner syndrome (45,X)

Ovarian failure

Amenorrhea

Infertility

Turner yndrome (45,X)

During the second trimester, edema was detected by ultrasonography

Thickened nuchal pad

Klinefelter syndrome (47,XXY)

Klinefelter's syndrome is a condition that occurs in men who have an extra X chromosome in most of their cells.

infertilitytestosterone

less facial and body hair

IQ: reduced to 10-20 point

Klinefelter syndrome (47,XXY)

Fragile X syndrome

High forehead

Large ears

Long face

Large testes

Prominent jaw

Learning difficulties are moderate to severe

FMR- 5Ⅰ ’ CGG

Normal 10-50 CGG

Intermediate 51-58

Premutation 58-200CGG

Full mutation >230CGG

Fragile X syndrome