Chromosomal

Anomalies

  Numerical Chromosomal
Abnormalities

 Changes in the number of chromosomes:

 Polyploidy
 Somatic cells contain multiples of haploid number of
chromosomes
 3n, 4n, 5n etc.

 Aneuploidy (Heteroploidy)
 Deviation from the diploid number of chromosomes

 2n + 1, 2n -1 etc.
 
Mechanism of Polyploidy

(a) Failure of pulling apart of 2 chromatids to

opposite ends after metaphase stage of mitosis.

(b) Reduplication of chromosomes without

dissolving of nuclear membrane.

(c) Failure of cytoplasmic division.

 
Types of Polyploidy

1. Autopolyploidy: even-numbered multiples of haploid

number of chromosomes. e.g.-

(a) Tetraploidy (23x4 or 92 chromosomes)

(b) Hexaploidy (23x6 or 138 chromosomes)

(c) Octaploidy (23x8 or 184 chromosomes)

etc.
  Types of Polyploidy

2. Allopolyploidy: odd-numbered multiples of haploid number

of chromosomes. e.g.-

(a) Triploidy (23x3 or 69 chromosomes)-common

(b) Pentaploidy (23x5 or 115 chromosomes)

(c) Heptaploidy (23x7 or 161 chromosomes)

etc.
 
Mechanism of Aneuploidy

Non-dysjunction: failure of separation of chromosomes during cell

division.

 Formation of 2 types of gametes (both abnormal)

 Fusion of either of these abnormal gametes with a normal

gamete can result in trisomy or monosomy

 May involve autosomes or sex chromosomes

Normal 1st & 2nd Two types of non-disjunction
meiotic division
  Trisomies of Chromosomes

 Presence of 3 copies of a chromosome

 Trisomy of Autosomes (13,18,21)

 Trisomy of Sex Chromosomes (XXX, XXY)

  Trisomy of Autosomes

 Trisomy 13 or D-trisomy (Patau syndrome)

 Trisomy 18 or E-trisomy (Edward syndrome)

 Trisomy 21 or G-trisomy (Down syndrome)

 
Trisomy 13 (Patau Syndrome)

 1st described by Bartholin (1657) & redefined by

Patau (1960).
 Chromosomal complement: 47,XX,+13 (female) or
47,XY,+13 (male)
 Phenotype: Male or female
 Incidence: 1:12,000 (increases with the age of
mother)
  Features of Patau Syndrome
 Mental deficiency  Malformed ears
 Low birth weight
 Congenital heart defects
 Abnormal development
 Renal tract anomalies
of frontal lobe
 Absence of corpus callosum  Microphthalmia

 Hypoplasia of cerebellum  Bilateral cleft lip/palate

 Sloping forehead  Polydactyly with

 Scalp defects rudimentary digits

 Rocker-bottom heel

Patau syndrome

Patau syndrome
  Trisomy 18 (Edward Syndrome)

 Chromosomal complement:
 47,XX,+18 (female) or
47,XY,+18 (male)
 Phenotype: Male or female

 Incidence: 1:8000
  Features of Edward Syndrome

 Mental deficiency  Low-set malformed ears

 Growth retardation  Ventricular septal defects

 Prominent occiput with  Renal anomalies

elongated head
 Clenched fists with
 Webbing of the neck overlapping of fingers
 Short sternum  Hypoplastic nails

 Micrognathia
 Edward syndrome
  Trisomy 21 (Down Syndrome)

 Chromosomal complement:
47,XX,+21 (female) or
47,XY,+21 (male)

 Phenotype: Male or female

 Incidence: 1:800 (increases with the age of mother)

  Features of Down Syndrome

 Short height  Malformed large ears

 Severe mental deficiency with  Epicanthal folds of the eyes

decline in the IQ with age
 Brushfield spots in iris
 Brachycephaly with flat face and
 Renal anomalies
occiput
 Prominent and protruding
 Flat and low nasal bridge
tongue (scrotal tongue)
 Upward slant to palpebral fissures
 Simian crease

 Clinodactyly of 5th digit


Down Syndrome
 Down syndrome
 Down syndrome

Down syndrome
  Trisomy of Sex
Chromosomes

 Klinefelter syndrome

 Triple X syndrome

 Double Y syndrome
 
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  Wide-set eyes

 Difficulty in speech, learning  Amenorrhoea

and emotional responses  Expressionless face

 Mild mental retardation in 15-  Enamel hypoplasia

25% cases  Deficient language skills
 Two sex chromatin Barr  Delayed development of
bodies motor skills

 Infertility
 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

A B C D E F G A B D E F G
 Loss of a (generally small) segment of chromosome

C
 Deletion
 Arise through spontaneous breakage
 some chromosomes have fragile spots
 radiation, UV, chemicals, viruses may increase
breakage
 Deletion
 May arise A B C D E F G

through unequal
x
crossing over
A B C D E F G

A B C D E G A B C D E F F 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 Angelman Syndrome

 Lack of muscle tone in  Developmentally delayed

newborn  Jerky movements

 Poor swallowing reflex  Stiff, fixed smile

 As adult - gross obesity  Uncontrolled laughter

 Mean I.Q. ~ 50  Abnormal E.E.G., epilepsy

 Microdeletion of 15  Microdeletion of 15
  Inversion

• 180o reversal of chromosome segment

A B C D E F G H I J K

180O

A B C H G F E D I J K
 
Inversion

• Produced through breakage and

reassociation of chromosome
D

A B
F G
 
Inversion
• Produced through breakage and
reassociation of chromosome

A B
F G
 
Types of Inversion

Paracentric Pericentric
 
REFERENCES

1. Essentials of Anatomy for Dentistry

Students,1st Edition.
2. Langman’s Medical Embryology,11th
Edition.
3. Human Embryology, 5th Edition.