The document provides information on various types of genetic disorders caused by chromosomal anomalies. It begins with definitions of key terms like aneuploidy, trisomy, monosomy, and discusses numerical and structural chromosomal anomalies. It then describes specific disorders in more detail, including Down syndrome, Edward syndrome, Patau syndrome, Turner syndrome, Klinefelter syndrome, Fragile X syndrome, Cri-Du-Chat syndrome, Wolf-Hirschhorn syndrome, Jacobsen syndrome, and Prader-Willi syndrome. It also discusses uniparental disomy and related disorders. In summary, the document defines genetic terminology and provides an overview of several important chromosomal anomalies and their associated genetic disorders
3. Definition & prevalence Chromosomal Anomalies = Missing, extra, or
irregular portion of chromosomal DNA.
Most foetus with some chromosomal abnormality
do not survive.
Affects approximately 1 out of 200 of new-borns.
Karyotype = Full set of chromosomes from an
individual. (Chromosomal Anomalies can be
detected via Karyotype Testing.)
Abnormalities depends on type of chromosome
affected due to non-disjunction chromosomes.
5. Important definitions in Genetics
Aneuploidy = Addition or loss of one (rarely two) chromosome.
Trisomy = 3 copies of a chromosome, (2n+1)
Tetrasomy = 4 copies of a chromosome, (2n+2)etc
Monosomy= 1 member of a chromosome pair missing, (2n-1) that is
only single copy of a chromosome is present.
Euploidy = Normal condition, where the genotype consists of complete
two sets of chromosomes (23+23 or 2n).
Genotype = Genetic make up of cell.
Karyotype = Number and appearance of chromosome in a nucleus.
Non disjunction = Incorrect separation of chromosomes or sister
chromatids during meiosis.
Phenotype = Characteristics of an Organism
Polyploidy = Entire extra set of chromosomes present, [can be
triploidy(3n= 69 chromosomes),tetraploidy(4n=92 chromosomes) etc.]
6. GENOTYPE
Genetic make up of a particular individual
Eg- 46XX/46XY/45XO
PHENOTYPE
Physical expression of that particular genotype
Eg-Male/Female
basics
7. Chromosome anomalies usually occur when there is an
error in cell division following meiosis or mitosis.
There are many types of chromosome anomalies.
They can be organized into two basic groups,
numerical and structural anomalies.
8. Numerical
This is called aneuploidy (an abnormal number of
chromosomes), and occurs when an individual is
missing either a chromosome from a pair (monosomy)
or has more than two chromosomes of a pair
(trisomy, tetrasomy, etc.).
Eg of numerical chromosomal anomalies are
Down syndrome, edward syndrome, patau syndrome
9. Classification of Genetic
Disorder
Single gene
disorders
Chromosoma
l Disorder
Autosomal
Numeric Structural
Sex
Chromosome
Numeric Structural
Multifactorial
Disorder
Acquired
Somatic
Genetic Disease
10.
11.
12.
13.
14.
15. Single chromosome disorder
Can happen in a chromosome itself, the
other is not required.
Deletion
(Genetic material
missing) may be
terminal or
interstitial.termina
l more common
Duplication
(Genetic material
present twice)
Inversion
(Genetic material is
“flipped”)
16. Two Chromosome Disorders Need 2 chromosomes to occur these processes.
Insertion
(Genetic material is added from
another chromosome)
Translocation
(Material is swapped(exchanged)
with another chromosome)
17. Common deletion
4P- WOLF HIRSCHHORN SYNDROME. THE MAIN
FEATURE ARE A TYPICAL GREEK HELMET FACIES
9P- MAIN FEATURE ARE CRANIFACIAL
DYSMORPHOLOGY WITH TRIGOCEPHALY
,SLANTED PALPEBRAL FEATURE
,EXOPTHALMUS,SECONDARY TO SUPRA ORBITAL
HYPOPLASIA
JACOBSON SYNDROME DELETION FROM
CHROMOSOME 11
18. Deletion in the 4p arm
Distinctive facial features -
prominent forehead, wideset eyes,
and broad beaked nose, collectively
described as "Greek warrior
helmet" features
Brain and muscles - profound
mental retardation, small head,
seizures (50% of individuals), low
muscle tone, poor muscle
development
Bones - very short stature, facial
deformities, malformations of
hands and feet, chest, and spine
Heart defects
Urinary and genitals -
malformations or
underdevelopment of organs
19.
20. Jacobsen Syndrome loss of genetic material
fromchromosome 11.
Most affected
individuals have
delayed development of
motor skills and speech,
cognitive impairment
and learning
difficulties, distinctive
facial features, and a
bleeding disorder
21. Cri-Du-Chat Syndrome
(chromosome 5p deletion syndrome)
Name is based on the infant’s cry. (high-pitched and
sounds like a cat.)
Incidence =1 in 216,000 birth
Normal 46 chromosomes but, missing a piece of
chromosome number 5.
Cat like cry of affected children ie meowing kitten
These babies are usually small at birth , have
respiratory problem
Microcephaly, micrognathia, low set ear
Wide set eye and downward slant of the eyes
22. Cri-Du-Chat Syndrome
(chromosome 5p deletion syndrome)
Cry is high pitched and similar to that of a meowing kitten.
Moon-shaped face
Malformed larynx
Difficulty swallowing and sucking (Feeding Problem).
Low birth weight and poor growth.
Severe cognitive, speech, and motor delays, mental
retardation
Behavioural problems such as hyperactivity, aggression,
and repetitive movements.
Excessive drooling(ptyalism)
24. Known disorders in humans include
Wolf-Hirschhorn syndrome, which is caused by partial
deletion of the short arm of chromosome 4; and
Jacobsen syndrome, also called the terminal 11q
deletion disorder.
25. Sex Chromosome Anomalies (Numeric)
Monosomy
Turner’s
syndrome
(45,X0)
Trisomies
Klinefelter's
syndrome
(47,XXY)
Jacob’s
syndrome
(47,XYY)
Triple x
syndrome
(47,XXX)
27. Fragile X syndrome
Also known as Martin-Bell syndrome; Marker X
syndrome.
Some consider this syndrome as X-linked dorminant,
some consider this as X-linked recessive which some
claims this to be not under X-linked dorminant or
recessive.
Genetic condition involving changes in the long arm of
the X chromosome.
Characterized by mental retardation.
Fragile area on X chromosome tends to repeat bits of the
genetic code .it is repetition of CGG gene in long arm of
x chromosome. (*More repeats, the more likely there is
to be a problem i.e intellilectual disabilities.)
Male and female can both be affected.
Male have only one X chromosome, single fragile X more
likely to affect them more severely.
28. Fragile x syndrome
Main feature in male
Mental retardation
Autistic behaviour
Large testicles (macro-orchidism)
Large size face and ear
Tendency to avoid eye contact
Hyperactive behaviour
Large forehead and/or ears with a prominent jaw
Hyper extensible finger joint
Female having varying degree of intellilectual and
learning disabilities
34. Turner Syndrome Sex chromosomal monosomy(45, XO)
99% of foetuses with Turner syndrome result in
spontaneous termination during the first
trimester.
Incidence = 1 in 5000 live birth
35. TURNER SYNDROME (Physical
impairments)
Short stature
Skeletal disorders (osteoporosis which may lead to
scoliosis)
Webbed neck(due to cystic hygroma)
Broad shoulders
Broad chest (shield chest), widely spaced nipples
No/Poor breast development
Narrow hips (High waist-to-hip ratio: hips are not much
bigger than waist)
Lymphedema of hands and feet
Shortened metacarpal IV
Cubitus valgus
Normal intelligence
36. TURNER SYNDROME (Clinical
Features)
Underdeveloped ovaries(streak gonads, hence this
syndrome also called ovarian dysgenesis)
Sterile, lack expected secondary sex characteristics
Amenorrhoea(No menstruation)
Cardiovascular problems in 40 % (Bicuspid aortic
valve,Coarctation of the aorta,aortic stenosis)
Renal anomalies 60% eg Horse shoe kidney
Thyroid problems (hypothyroidism specifically
Hashimoto's thyroiditis).
37.
38.
39. Klinefelter’s syndrome
XXY Males
Disorder occurring due to nondisjunction of
the X chromosome during Meiosis.
Extra X chromosome is nondisjunction during
meiosis II of the germ cell in the female.
Occur when sister chromatids on the X sex
chromosome fail to separate.
XX ovum produced and when fertilized with a Y-
sperm it yields XXY offspring.
Also occurs X and Y sex chromosomes fail to
separate, producing a sperm with an X and Y
chromosome & fertilize with normal X ovum
produces XXY offspring.
Incidence = 1 in 580 live male births.
41. Klinefelter’s syndrome Clinical
features Childhood
Weaker muscles and reduced strength.
Puberty (features become more prominent due to hypogonadism (less amount
of testosterone produced): so generally dianosed at puberty.
Phenoypically male
Rounded body type
Broader hips
Little body hair is present
Gynecomastia (increased breast tissue)
Microorchidism (i.e. small testicles)
Azospermia leading to infertility
Micropenis
Tall stature
IQ is normal ,those having higher x chromosome counts
show impaired cognition each addition x chromosome
reduces iq 10-15 points.
45. INTRODUCTION
Generally in sexual reproduction, the organism bear diploid number of chromosomes i.e they
contain two set of homologous chromosomes. Out of these two sets of chromosomes one
inherited from the mother and other from father.
In some cases zygote is diploid , but both chromosomes are exceptionally inherited from only
one parent(from only mother or father) is called uniparental disomy (UPD).
Fig:1 showing the normal zygote and uniparental
disomic zygote
46. When the both chromosomes inherited from only mother called maternal UPD. Mat UPD has
been observed on 2,7,14,15, X chromosome. It is meiotic in origin.
When the both chromosomes inherited from only father called paternal UPD. Pat UPD has
been observed on 6,11,15,20, X and XY chromosome. It is mitotic in origin.
The most common mechanisms leading to UPD include chromosomal non disjunction in the first
or second meiotic division, but sometime errors in mitosis and somatic recombination may also
lead to UPD.
UPD may lead to disorders because maternal and paternal genomes are not equivalent on all
chromosome.
UPD syndromes
• Prader-Willi syndrome (PWS)
• Angelman syndromes (AS)
• Beckwith-Wiedemann syndrome(BWS)
50. ANGELMAN SYNDROME (AS)
Angelman syndrome (AS) is a neuro genetic disorder. It is caused by the loss of normal maternal
chromosome 15q11-13.
Symptoms
severe mental retardation
• development delay
• Severe speech impairment , , absent speech
• Problems with movement and balance (ataxia).,epilepsy
• Behavior uniqueness any combination frequent laughter/ smiling apparent happy demeanor,
easily excitable personality, sleep disturbance.
• Unusually fair skin with light coloured hair.
Angelman syndrome affects an estimated 1 in 12,000 to 20,000 peoples.
