Chromosomal Anomalies (Lecture 2)

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Chromosomal Anomalies
(Lecture 2)
30.10.2014

• Dr. Archana Rani
• Associate Professor
• Department of Anatomy
• KGMU UP, Lucknow

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Trisomy of Sex Chromosomes

• Klinefelter syndrome
• Triple X syndrome
• Double Ysyndrome

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Klinefelter Syndrome

• Chromosome complement 47,XXY
• Phenotype Male
• Incidence 11000

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Features of Klinefelter Syndrome

• Tall stature thin build long lower limbs
• Testicular atrophy
• Female pattern of pubic hair
• High pitched voice
• Infertility (aspermatogenesis)

• Gynaecomastia
• Low level of intelligence
• Serum testosterone levels low to normal
• FSH and LH levels very high
• Sex chromatin positive

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Klinefelter syndrome Karyotype
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Klinefelter Syndrome
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Triple X Syndrome (Superfemale)

• Chromosome complement 47,XXX
• Phenotype Female
• Incidence 11000

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Features of Triple X Syndrome

• Normal in appearance
• Difficulty in speech, learning and emotional
  responses
• Mild mental retardation in 15-25 cases
• Two sex chromatin Barr bodies
• Infertility

• Wide-set eyes
• Amenorrhoea
• Expressionless face
• Enamel hypoplasia
• Deficient language skills
• Delayed development of motor skills

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Superfemale Karyotype
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Superfemale
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Double Y Syndrome

• Chromosome complement 47,XYY
• Phenotype Male
• Incidence 11000

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Features of Double Y Syndrome

• Normal in appearance
• Tall stature
• Aggressive behaviour
• Problems in motor and language development

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Monosomies of Chromosomes

• Presence of only one member of a chromosome pair
  in a karyotype
• More detrimental than equivalent trisomy
• Can involve autosomes or sex chromosomes
• Usually abort spontaneously
• Monosomy of X chromosome results in XO condition
  called Turner syndrome

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Turner Syndrome

• Chromosome complement 45,XO
• Phenotype Female
• Incidence 15000-8000

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Features of Turner Syndrome

• Short statured female
• Sexual infantilism with primary amenorrhoea and
  sterility
• Short, webbed neck
• Prominent ears with defective hearing
• Small mandible
• Defective vision

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Features of Turner Syndrome

• Epicanthal folds
• Low posterior hair line
• Cubitus valgus
• Broad chest with widely spaced nipples
• Cardiovascular anomalies
• Hyperconvex finger nails
• Pigmented nevi
• Sex chromatin negative

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Turner Syndrome Karyotype
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Turner Syndrome
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Structural Chromosomal Abnormalities

• Results from chromosome breakage
• Followed by reconstitution in an abnormal
  combination
• Breaks in any chromosome may be induced by
  various factors

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Structural Chromosomal Abnormalities

• Deletion (Deficiency)
• Inversion
• Translocation
• Isochromosome
• Ring Chromosome

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Deletion

• Loss of a (generally small) segment of chromosome

A B D E F G
A B C D E F G
C
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Deletion

• Arise through spontaneous breakage
• some chromosomes have fragile spots
• radiation, UV, chemicals, viruses may increase
  breakage

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Deletion

• May arise through unequal crossing over

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Deletion

• Large deletions will most probably be lethal
• Smaller deletions may allow survival
• E. coli deletions of up to 1 have been
  observed in living cells
• D. melanogaster deletions of up to 0.1
  observed

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Deletions in Humans

• Cri-du-chat syndrome
• Micro deletion of chromosome 5
• Di-George syndrome
• Micro deletion of chromosome 22
• Schizophrenia Obsessive Compulsive Disorder
• Micro deletion of chromosome 22 associated
• Angelman syndrome
• Micro deletion of chromosome 15
• Prader-Willi syndrome
• Micro deletion of chromosome 15

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Cri-du-chat syndrome

• 1st autosomal deletion described
• Characteristic cat-like cry, which disappears
  with age
• Microcephaly
• Severe mental retardation
• Congenital heart disease
• Hypertelorism (widely separated eyes)
• Low birth weight and poor growth
• Severe cognitive, speech, and motor delay
• Behavioral problems
• Excessive drooling

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Cri-du-chat syndrome
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Prader-Willi and Angelman Syndromes
Prader-Willi Syndrome
Angelman Syndrome

• Lack of muscle tone in newborn
• Poor swallowing reflex
• As adult - gross obesity
• Mean I.Q. 50
• Microdeletion of 15

• Developmentally delayed
• Jerky movements
• Stiff, fixed smile
• Uncontrolled laughter
• Abnormal E.E.G., epilepsy
• Microdeletion of 15

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Inversion

• 180o reversal of chromosome segment

A B C D E F G H I J
K
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Inversion

• Produced through breakage and
  reassociation of chromosome

D
E
C
B
A
F
G
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Inversion

• Produced through breakage and
  reassociation of chromosome

D
E
C
B
A
F
G
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Inversion

• May change phenotype through position effects
• move active genes to sites generally inactive
  lose gene function
• move inactive genes to sites generally active
  gain gene function
• May act to preserve blocks of genes (specific
  alleles) which function well together

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Types of Inversion

• Paracentric

• Pericentric

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Translocation

• Exchange of segments between non-homologous
  chromosomes

F
E
D
L
M
N
O
P
C
B
Q
A
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Translocation
A B C
O N M L
D E F
Q P
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Isochromosome

• Centromere of the chromosome divides transversely
  instead of longitudinally
• One arm is missing and the other arm duplicated

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Ring Chromosome

• Occurs due to loss of both the ends of a
  chromosome
• The broken ends rejoin to form a ring-like
  chromosome
• Rare anomaly

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Robertsonian Changes

• Fusion
• two chromosomes join to form one

• Fission

one chromosome splits to form two
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REFERENCES

• 1. Essentials of Anatomy for Dentistry
  Students,1st Edition.
• 2. Langmans Medical Embryology,11th Edition.
• 3. Human Embryology, 5th Edition.

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MCQs

• 1. Klinefelter syndrome is associated with
  chromosome complement
• a) 47,XXX
• b) 47,XXY
• c) 47,XYY
• d) 47,YYY

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MCQs

• 2. Testicular atrophy is associated with
• a) Triple X syndrome
• b) Double Y syndrome
• c) Turner syndrome
• d) Klinefelter syndrome

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MCQs

• 3. Sex chromatin negative is a characteristic
  feature of
• a) Triple X syndrome
• b) Down syndrome
• c) Turner syndrome
• d) Klinefelter syndrome

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MCQs

• 4. All of the following are trisomy of sex
  chromosomes except
• a) Turner syndrome
• b) Klinefelter syndrome
• c) Triple X syndrome
• d) Double Y syndrome

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MCQs

• 5. Partial deletion of short arm of chromosome 5
  is a feature of
• a) Angelman syndrome
• b) Prader -Willi syndrome
• c) Cri-du-chat syndrome
• d) All of the above