Chromosomal Disorders

Disorders of the autosomes

Disorders of the sex chromosomes

 Chromosomal Abnormalities
NUMERICAL STRUCTURAL

Aneuploidy Deletion
Monosomy Duplication
Trisomy Inversion
Tetrasomy Paracentric inversion
Pericentric inversion
Polyploidy
Ring chromosome
Triploidy Isochromosome
Tetraploidy Translocation
Reciprocal
Robertsonian

Emery of Medical genetic

 Numerical:
dependent in the number of chromosome
(increase/decreased) (duplicated / not)
1.Aneuploidy (monosomy, trisomy, tetrasomy)
the increase of one chromosome or missing
one chromosome ( certain chromosomes)
2.Polyploidy (triploidy, tetraploidy) the whole
chromosome number is increased
(duplicated/ more than duplicated )
 Numerical Abnormalities

1. Aneuploidy
Monosomy(45,X : Turner Syndrome)
Trisomy (47,XY,+21 : Down Syndrome)
Tetrasomy(48,XXXX)

2. Polyploidy
Triploidy(69,XXY)
Tetraploidy(92,XXYY)
Monosomy and Trisomy
Balance and Unbalanced
Translocation
Isochromosome
Chromosomal Abnormalities;
Numerical - Aneuploidy
 Sex Chromosomes
Abnormalities
Sex Chromosome Aneuploidy ( which means the number is
increased , it could be 1 2 3 4 X chromosome in a person )
Sex Chromosome Aneuploidy is more common than
Autosome Aneuploidy
In order to survive and develop embryo needs at least one
X chromosome. 45, Y is lethal because there is no X.
In healthy females, one X chromosome will be inactivated in
each somatic cell. The inactivated X chromosome is
referred to as a Barr body.
An individual who has an intact Y-chromosome will be male,
regardless of the number of X chromosomes he possesses.
In the absence of an intact Y chromosome an individual will
be female. ( X chromosome is much larger than Y )
Abnormalities of the increased number most of them
survive normally: X0, xxy, xxxy, xxxxy they will survive
 X-Chromosomal Disorders
Imbalances of X-chromosomes are better tolerated than those of
autosomes
Increased number of X-chromosomes in either males or females lead
to mental retardation
LyonizationMary Lyon : during 16th day of embryonic life one X-
chromosome in females is randomly inactivated
A woman with the chromosome constitution 47, XXX should have 2
Barr bodies in each cell.
XXY individuals are male, but have a Barr body.
XO individuals are female but have no Barr bodies.
1 Barr bodies: female ; none : male ; 2,3 Barr bodies depend on
how many X they have
Always the number of barr bodies = the total X 1 , because the
active one will not be able to make Barr bodies

Xy sperm because the is non-disjunction during meiosis

46,Xy is lethal because you are getting the x from different person
Chromosomal Abnormalities;
Numerical - Polyploidy
Karyotyping Result
 Isochromosome xq
Chromosome Disorder
 Trisomy13, Patausyndrome
More severe than Trisomy 21; (1 in 15 -25,000 births)

Clinical Features :
Microcephaly and mental retardation, scalp defect,
microphthalmia, often blind ( only one eye sometimes)
Cleft lip/palate, polydactyly, rocker-botton feet,
abnormal ears, apneicspells and myotonic seizures,
cardiac dextroposition and VSD, extensive visceral
defects
CNS malformations presence of a single forebrain
hemisphere or lobe
Half of such individuals die within the first month--the
remainder by 1 year-
Clinical Features: Trisomy 18
more severe disease
Prominent occiput
Short palpebral fissures
Micrognathia
Low-set, malformed ears
Profound Mental Retardation
Rocker-Bottom Feet
Short Sternum
Small Pelvis
Clenched Hands
Renal anomalies
Cleft Lip/Palate
Hypoplasticthumbs
Dorsiflexedhalus(hammer toe)
Renal Anomalies
Clinical feature (1 in 7,500 births)
Trisomy18Edwards syndrome very typical cannot survive for long
Karyotype: 47, XX (or XY), +18
Survival 50% within 1 month, 50% within less than 1 year.
polydactyly, very low set of ear , cannot survive for long
diagnosis by culture or we can do FISH (fluorescence in situ hybridization)
So this is about autosomal chromosomal abnormalities
 Turner syndrome

Monosomy X or X0
1 in every 5000 births
webbed neck very wide neck
short stature
sterile also the nipples are very far from Each other ,
they have abnormalities of the aorta , elbow , spots all
over the body (pegmintation)
KARYOTYPING : possibilities of chromosomal abnormalities
Classical 45X
Isochromosome46,X,i(Xq)
Deletion 46XXq-
Deletion 46XXp-
Ring 46,X r(X)
Mosaic e.g. 45,X/46,XX
 47,XYY
Clinical Features :
when they discover this they were
claim that this has something to do
with criminality ( extra Y ) , but they
were wrong, they just become more
aggressive people
 47,XYY
Not obviously abnormal
No marked physical or behavioral phenotype
Tall, fertile, may have severe acne during adolescence
Incidence1/1000
Increased risk of educational or behavioral problems
IQ scores about 10 pts below average
Attention deficits
Hyperactivity
Impulsiveness
Origin of the error that leads to XYY karyotype must be
paternal nondisjunction at meiosis II producing YY sperm
 Sex chromosome Tetrasomy, Males: 48,XXXY
Clinical Features:
They have difficult in sexual development , generally the are mentally impaired
not mental retardation (low IQ )
Reduction in intellectual functioning IQ between 20-80
Fertilization of this sperm by an egg will lead to turner syndrome
Coarse facial appearance, gonadal hypoplasiacommon
As a rule: additional X chromosomes cause a more abnormal phenotype -more
defective sexual development and mental impairment.

Sex Chromosome Pentasomy, Males : 49,XYYYY

Clinical Features
Tall stature
Aberrant behavior (impulsivity, low frustration tolerance)
Low-normal or subnormal intelligence
Developmental delay
Testicular abnormalities
Some craniofacial dysmorphisms(more common for 49,XYYYY)
 INSTABILITY OF
CHROMOSOMES
Instability of chromosome : the number is
normal
Chromosome breaks
Once chromosome broken by some means
Unstable situation as telomeres not at end
Usually join up to other piece