Chromosomal Anomalies (Lecture 2) Dr. Archana Rani Associate Professor Department of Anatomy KGMU UP, Lucknow 30.10.2014.

Chromosomal Anomalies (Lecture 2)

Dr. Archana Rani

Associate Professor

Department of Anatomy

KGMU UP, Lucknow

30.10.2014

Trisomy of Sex Chromosomes

• Klinefelter syndrome

• Triple X syndrome

• Double Ysyndrome

Klinefelter Syndrome

• Chromosome complement: 47,XXY

• Phenotype: Male

• Incidence: 1:1000

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

Klinefelter syndrome: Karyotype

Klinefelter Syndrome

Triple X Syndrome (Superfemale)

• Chromosome complement: 47,XXX

• Phenotype: Female

• Incidence: 1:1000

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

Superfemale: Karyotype

Superfemale

Double Y Syndrome

• Chromosome complement: 47,XYY

• Phenotype: Male

• Incidence: 1:1000

Features of Double Y Syndrome

• Normal in appearance

• Tall stature

• Aggressive behaviour

• Problems in motor and language development

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

Turner Syndrome

• Chromosome complement: 45,XO

• Phenotype: Female

• Incidence: 1:5000-8000

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

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

Turner Syndrome: Karyotype

Turner Syndrome

Structural Chromosomal Abnormalities

• Results from chromosome breakage

• Followed by reconstitution in an abnormal combination

• Breaks in any chromosome may be induced by various factors

Structural Chromosomal Abnormalities

• Deletion (Deficiency)

• Inversion

• Translocation

• Isochromosome

• Ring Chromosome

Deletion

• Loss of a (generally small) segment of chromosome

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

C

Deletion

• Arise through spontaneous breakage– some

chromosomes have fragile spots

– radiation, UV, chemicals, viruses may increase breakage

Deletion

• May arise through unequal crossing over A B C D E F G

A B C D E F G

x

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

Deletion Duplication

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

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

Cri-du-chat syndrome

Prader-Willi and Angelman Syndromes

Prader-Willi Syndrome

• Lack of muscle tone in newborn

• Poor swallowing reflex• As adult - gross obesity• Mean I.Q. ~ 50• Microdeletion of 15

Angelman Syndrome• Developmentally

delayed• Jerky movements• Stiff, fixed smile• Uncontrolled laughter• Abnormal E.E.G.,

epilepsy• Microdeletion of 15

Inversion

• 180o reversal of chromosome segment

A B C D E F G H I J K

A B C H G F E D I J K

180O

Inversion

• Produced through breakage and reassociation of chromosome

A B

C

D

E

F G

Inversion

• Produced through breakage and reassociation of chromosome

A B

C

D

E

F G

Types of Inversion

Paracentric Pericentric

Translocation

• Exchange of segments between non-homologous chromosomes F

A

B

C

DE

L M NO

P

Q

Translocation

A B C

D E F

O N M L

Q P

Isochromosome

• Centromere of the

chromosome divides

transversely instead

of longitudinally

• One arm is missing

and the other arm

duplicated

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

Robertsonian Changes

• Fusiontwo chromosomes join to form one

• Fission

one chromosome splits to form two

REFERENCES

1. Essentials of Anatomy for Dentistry

Students,1st Edition.

2. Langman’s Medical Embryology,11th Edition.

3. Human Embryology, 5th Edition.

MCQs

1. Klinefelter syndrome is associated with

chromosome complement:

a) 47,XXX

b) 47,XXY

c) 47,XYY

d) 47,YYY

MCQs

2. Testicular atrophy is associated with:

a) Triple X syndrome

b) Double Y syndrome

c) Turner syndrome

d) Klinefelter syndrome

MCQs

3. Sex chromatin negative is a characteristic feature of:

a) Triple X syndrome

b) Down syndrome

c) Turner syndrome

d) Klinefelter syndrome

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

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