chromosomal disorders

1. Chromosomal disorders

2. Body, cells, chromosomes
Human body: 10 trillion cells
A normal human karyotype has 46
chromosomes (23 pairs):
#1-22 are called autosomes
#23 are called sex chromosomes

3. XX~
female
XY~
male

4. Cytogenetics
- karyotype
karyogram

5. Homologous chromosomes
Daughter chromosomes
Sister chromatids

6. Structural disorders
translocations
Insertions/
deletions
duplications inversions
Ring
chromosomes
Numerical disorders
Aneuploidy
Hyperploidy
Trisomy
(2n+1)
Tetrasomy
(2n+2)
Hypoploidy
Monosomy
(2n-1)
Nullisomy
(2n-2)
Euploidy
Monoloidy
(n)
Diploidy
(2n)
Polyploidy
(3n,4n,etc.)
Chromosomal aberrations
Aberration in a cell vs. in every cell of an organism

7. • Baby has wrong chromosome number
–trisomy
• cells have 3 copies of a chromosome
–monosomy
• cells have only 1 copy of a chromosome
trisomy
2n+1
monosomy
2n-1

8. 1. Deletion
• Loss of all or part of a
chromosome

9. Chromosomal deletion syndromes
Wolf–Hirschhorn syndrome (4p16.3)
Jacobsen syndrome (11q24.1)
Chri du chat szindróma (5p15.1)

10. 2. Duplication
• Produce extra copies of parts
of a chromosome.

11. Chromosomal duplication syndromes
Charcot–Marie–Tooth disease
1q21.1 duplication
syndrome
Mutations on various chromosomes can cause the disease

12. 3. Inversion
• Part of a chromosome breaks
out and reinserts backwards.

13. 4. Translocation
• Part of a chromosome breaks
off & attaches to another
chromosome

14. Numerical aberrations
Autosomes
Patau-
syndrome
(13-trisomy)
Edwards-
syndromes
(18-trisomy)
Down-
syndrome
(21-trisomy
Sex
chromosomss
Turner-
syndrome
(X0)
Triple X
syndrome
(XXX)
Klinefelter
syndrome
(XXY)
Double Y
syndrome
(XYY)

15. Patau-syndrome
(trisomy 13)
A chromosomal condition associated with severe intellectual disability and
physical abnormalities in many parts of the body. Affected individuals
with this disorder often have brain or spinal cord abnormalities, heart
defects, poorly developed eyes, extra fingers or toes, an opening in the lip
frequently associated with an opening in the roof of the mouth, and weak
muscle tone (hypotonia).
Many infants with trisomy 13 die within their first days or weeks of life.
Only 5 to 10 percent of children with this condition live past their first year.

16. Patau Syndrome
Manifestations of the disease
- severe congenital malformations
- moderate microcephaly,
- violation of the development of various
departments of the central nervous system,
- low sloping forehead
- narrowed palpebral fissures, the distance between
- which is reduced, microphthalmia, clouding of
the cornea,
- sunken nose bridge, wide base of the nose,
- deformed auricles,
- cleft upper lip and palate, polydactyly,
- flexor position of the hands, short neck.
- delayed mental development is characteristic.
Due to severe congenital malformations, most children with Patau
syndrome die in the first weeks or months (95% - up to 1 year)

17. Patau Syndrome

18. Edwards syndrome
(trisomy 18)
This chromosomal condition may be associated with
heart defects and abnormalities of other organs. Other
features include a small, abnormally shaped head; a
small jaw and mouth; and clenched fists with
overlapping fingers. Most affected individuals die before
birth or within their first month.
5 to 10 % of children with this condition live past their first year, and
these children often have severe intellectual disability.

19. Edwards syndrome
(trisomy 18)

20. Down-syndrome
(trisomy 21)
This syndrome is associated with a characteristic facial appearance, and
hypotonia in infancy. Affected individuals experience cognitive delays, but
the intellectual disability is usually mild to moderate. About half of all
affected children are born with a heart defect. Individuals with Down
syndrome also have an increased risk of hearing and vision problems.

21. Down-syndrome
(trisomy 21)

22. Typical symptoms of patients with
Down syndrome
 “Flat face” - 90%
 Brachycephaly (abnormal
shortening of the skull) - 81%
 Skin fold on the neck in
newborns - 81%
 Mongoloid eye incision - 80%
 Еpicant (vertical skin fold
covering the medial angle of
the palpebral fissure) - 80%

23. Typical symptoms of patients with Down syndrome
• brachymesophalangia (shortening of all fingers due to
underdevelopment of the middle phalanges) -70%
• open mouth (due to low muscle tone and special
structure of the palate) - 65%
• flat nose - 52%
• transverse palmar fold (also called “monkey” - 45%
• short wide neck - 45%
• short nose - 40%

24. Down-syndrome
• Most men with Down syndrome are infertile.
At least 50% of women with Down syndrome
can have children. 35-50% of babies born to
mothers with Down syndrome are born with
Down syndrome or other abnormalities.

25. Cri-du-chat syndrome
 Terminal deletion of the short arm end of the chromosome 5
 Child has a weak catlike cry
 Mental retardation , microcephaly , heart disease.

26. Cri-du-chat syndrome
• One human disorder cased by a
heterozygous deletion is Cri-du-chat
syndrome which results from an
observable deletion of part of the
short arm of chromosome 5 (5p-),
one of the larger human
chromosomes.

27. Cri-du-chat syndrome
• Children with cri-du-chat
syndrome are severely mentally
retarded, have a number of
physical abnormalities,
muscular hypotony, moon-like
face, microcephalia, low-set
malformed ears, anti-
mongoloid eyes and cry with a
sound like the mew of a cat
(hence the name, which is
French for “cry of the cat”).
Duration of life is only 14% of
affected children die before the
age of ten year.

28. Turner syndrome (X0)
The most common feature of this syndrome is short stature. Many affected girls do
not undergo puberty unless they receive hormone therapy, and most are infertile.
Turner syndrome occurs in about 1 in 2,500 newborn girls worldwide.

29. Turner syndrome (X0)
Symptoms
- women get sick
- short stature
- short neck, bilateral
membrane of the neck (a
very characteristic, but
optional symptom);
- hair growth on the lower
border of the neck;
- the absence of most
secondary -sexual
characteristics,
- infertility,
- mental retardation

30. wing-shaped folds on the neck "head
of the sphinx"

31. Triple X syndrome (XXX)
Most females with triple X syndrome are able to conceive children. This condition is
associated with an increased risk of learning disabilities and delayed development of
speech and language skills. Delayed development of motor skills, hypotonia, and
behavioral and emotional difficulties are also possible.
This syndrome occurs in about 1 in 1,000 newborn girls.
Four or even more X chromosome can also occur.

32. • XXX 47, XXX (triplo-X)
– 1 in every 2000 live births
– produces healthy females
• Why?
• Barr bodies
– all but one X chromosome is inactivated

33. • About 1 in 1.000 females born have three
X-chromosomes instead of the normal two.
These 47, XXX (triplo-X) females are mostly
completely normal, although they are
slightly less fertile and a small number have
less than average intelligence. Barr bodies
are two.

34. Klinefelter syndrome (XXY)
This disease affects male physical and cognitive development. Affected individuals
typically have small testes that do not produce as much testosterone as usual. A shortage of
testosterone can lead to delayed or incomplete puberty, breast enlargement, reduced facial
and body hair, and infertility. have an increased risk of developing breast cancer and a
chronic inflammatory disease. Children with Klinefelter syndrome may have learning
disabilities and delayed speech and language development.
Klinefelter syndrome affects 1 in 500 to 1,000 newborn males.

35. Klinefelter Syndrome
 Presence of breasts
 Gynecomastia
(excessive development
of male mammary
glands)
 Small testes,
aspermatogenesis due to
hyalinization of
seminiferous tubules
 Less intelligent

36. Klinefelter Syndrome

37. Double Y syndrome(XYY)
Males with this condition may be taller than average, this chromosomal change
typically causes no unusual physical features. Most males with 47,XYY
syndrome have normal sexual development and are able to father children. This
syndrome is associated with an increased risk of learning disabilities and delayed
development of speech and language skills. Delayed development of motor
skills, hypotonia, and behavioral and emotional difficulties.
This syndrome occurs in about 1 in 1,000 male birth.

38. • These 47, XYY individuals are male because of
the presence of the Y. The XYY karyotype
results from nondisjunction of the Y-
chromosome in meiosis. About 1 in 400 males
born have XYY syndrome with following
features: they are taller than normal people,
has reduced intelligence, more aggressive than
normal males, over produces male hormones
like testosterone, has criminal and brutal
tendencies.