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By : Gan Quan Fu, PT,
MSc Human Anatomy (Batch 3)
Classification of Genetic Disorder
Definition & Prevalence
Numeric Chromosomal Anomalies
Structural Chromosomal Anomalies
Sex Chromosome Anomalies
Numeric Chromosomal Anomalies
Structural Chromosomal Anomalies
Important definitions in Genetics
Classification of Genetic
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-
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.
Autosomal Anomalies (Numeric)
Single copy of an
Lethal in early
(47 + 13)
(47 + 18)
(47 + 21)
An additional chromosome 13 resulting
from nondisjunction during meiosis.
Incidence = 1 in 10,000 -20,000 live
More than 80% die within the first year of
Anomalies can be seen on:
Nervous & Optic System
Musculoskeletal & Cutaneous
Urogenital & Cardiovascular System
Intellectual disability and motor disorder
Holoprosencephaly (failure of the forebrain to
Structural eye defect:
Peters anomaly (a type of eye abnormality)
Iris and/or fundus (coloboma)
Retinal dysplasia or retinal detachment
Cortical visual loss
Optic nerve hypoplasia
Meningomyelocele (a spinal defect)
Polydactyly (extra digits)
Congenital trigger digits
Deformed feet known as rocker-bottom feet
Omphalocele (abdominal defect)
Abnormal palm pattern
Overlapping of fingers over thumb
Cutis aplasia (missing portion of the skin/hair)
A. Midline defect with
cleft lip & palate.
B. Clenched hand with
C. Postaxial polydactyly.
E. Punched out aplasia
cutis scalp lesions.
An additional chromosome 18 resulting from
nondisjunction during meiosis.
Incidence =1 in 6000 - 8000 live birth.
Majority of fetuses with this syndrome die
before birth; >90% dead in 1st year.
80% affected were females.
Small head (microcephaly) accompanied by a prominent
back portion of the head (occiput),
Low-set, malformed ears,
Abnormally small jaw (micrognathia),
Cleft lip/cleft palate,
Narrow eyelid folds (palpebral fissures),
Widely spaced eyes (ocular hypertelorism),
Drooping of the upper eyelids (ptosis),
A short breast bone,
Choroid plexus cysts
Underdeveloped thumbs and/or nails
Webbing of the second and third toes, clubfoot or rocker
Males will have undescended testicles.
An additional chromosome 21 resulting from
nondisjunction during meiosis. (*Extra
chromosome 21 in every cell of the body)
John Langdon Down (the British physician)
who described the syndrome in 1866.
Karyotype = 47,XX+21 or 47,XY+21
Characteristics Percentage Characteristics Percentage
Mental impairment 99% Abnormal teeth 60%
Stunted growth 90% Slanted eyes 60%
Umbilical hernia 90% Shortened hands 60%
Increased skin back
80% Short neck 60%
Low muscle tone 80%
Narrow roof of
76% Bent fifth finger tip 57%
Flat head 75%
Brushfield spots in
Flexible ligaments 75%
Large tongue 75% Protruding tongue 47%
Abnormal outer ears 70%
Flattened nose 68% Strabismus ~35%
Separation of first
and second toes
Can happen in a chromosome itself,
the other is not required.
(Genetic material is
Need 2 chromosomes to occur these
(Genetic material is added from
(Material is swapped(exchanged)
with another chromosome)
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.
Most cases are believed to occur during the
development of the egg or sperm, small
number of cases occur when a parent passes
a different, rearranged form of the
chromosome to their child.
Cry is high pitched and similar to that of a
Difficulty swallowing and sucking (Feeding
Low birth weight and poor growth.
Severe cognitive, speech, and motor delays,
Behavioural problems such as hyperactivity,
aggression, and repetitive movements.
Sex Chromosome Anomalies
Sex chromosomal monosomy(45, XO)
99% of foetuses with Turner syndrome result
in spontaneous termination during the first
Incidence = 1 in 2000-5000.
Skeletal disorders (osteoporosis which may lead
Webbed neck(due to cystic hygroma)
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
Underdeveloped ovaries(streak gonads,
hence this syndrome also called ovarian
Sterile, lack expected secondary sex
Cardiovascular problems (Coarctation of the
aorta, Bicuspid aortic valve)
Horse shoe kidney
Thyroid problems (hypothyroidism
specifically Hashimoto's thyroiditis).
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 500 live male births.
Weaker muscles and reduced strength.
Puberty (features become more prominent due to
hypogonadism (less amount of testosterone produced):
Rounded body type
Little body hair is present
Gynecomastia (increased breast tissue)
Microorchidism (i.e. small testicles)
Azospermia leading to infertility
IQ is normal
Characterized by the presence of an
additional Y chromosome.
Incidence = 1 in 1,800 births
Increase in testosterone
There are article which claims that those
with Jacob’s Syndrome are more prone in
Characterized by the presence of an additional X
When an XX ovum fertilizes with X- sperm.
Incidence = 1 in 1,000 birth
Normal physically, Sometimes taller.
Normal mentally, Increase risk of retardation
and learning difficulties.
Genotype Gender Syndrome Physical Traits
XY Male -
sterility, small testicles,
XYY Male XYY or Jacob’s
normal male traits
XX Female -
XO Female Turner Syndrome sex organs don’t mature
at adolescence, sterility,
XXX Female Triple X tall stature, learning
disabilities, limited fertility
Sex Chromosome Anomalies
Also known as ‘holandric inheritance’.
Determination of a phenotypic trait by an
allele (or gene) on the Y chromosome.
Pass from father to son with no
interchromosomal genetic recombination
Deletion (missing genetic materials) in Y-
gene is a frequent genetic cause of male
Having hairy ears was once thought to be a
Y-linked trait in humans, but that hypothesis
has been discredited.
Single gene disorders that reflect the presence
of defective genes on the X chromosome.
Show inheritance patterns that differ from
Male have one X chromosome + a Y chromosome
while females have 2 X chromosome, they show
different patterns of inheritance and severity of
manifestation. (There are both dominant and
recessive X-linked diseases, also there are some
characteristics that are common to X-linked
disorders in general).
Males are never carriers, if they have a mutated
gene on the X chromosome, it will be expressed.
Males are termed hemizygous for genes on the X
Expressed in females when only a single copy of the mutated
gene is present.
Very few diseases have been identified:
Nephrogenic Diabetes Insipidus
Hypophosphatemic rickets or vitamin D resistant rickets
(leading to low serum phosphorus & skeletal abnormalities)
Never passed from father to son.
Affected males produce only affected females. (An affected male
only has one X chromosome to pass on to his daughters.
Affected females produces 50% normal and 50% affected
Males are usually more severely affected than females. Some X-
linked traits may even be lethal.
Females are more likely affected. (They have 2x increase risk to
inherit the mutated allele, since they have 2X chromosomes)
Inherited, heterogeneous disorders involving
basement membranes of kidney, frequently affecting
the cochlea and eyes.
Hypertension with edema and nephrotic syndrome at
Sensorineural deafness (90% are deaf by age of 40 years)
Diffuse leiomyomatosis of the esophagus and
Occurs when the kidneys cannot concentrate
urine normally resulting excretion of large
amount of dilute urine. *Kidney tubules do not
respond to Antidiuretic Hormone (ADH).
Intense or uncontrollable thirst, and crave
Produce large amounts of urine (usually
more than 3 liters, and up to 15 liters per
Form of rickets characterized by low serum
Resistance to treatment with ultraviolet
radiation or vitamin D ingestion.
Incidence = 1 in 20,000 newborns
Associated with this condition is disproportionate,
resulting from deformity and growth retardation of the
Bow Legged and deformities associated with
Bone Pain and Joint Pain
Hereditary pattern which a recessive gene in X
chromosome results in:
Male : Manifestation of characteristics
Female : Carrier (Usually)
Males are more likely affected, they only need
one copy of mutant allele to express phenotype.
Female must have 2 copies of the mutant allele
in order for the mutant phenotype to develop.
Female with 1 copy of the mutant allele is only a
Duchenne Muscular Dystrophy
Also known as colour vision deficiency (CVD).
Mix of colours mentioned above.
Rarely that a person sees no color at all.
Three types of cone cells in eye (each type
senses either red, green, or blue light most
concentrated in macula). Individuals with colour
blindness do not have these cone cells.
Incidence = Approximately 1 in 12 men (8%); 1 in
Form of muscular dystrophy (muscle
weakness and loss of muscle tissues) which
Caused by a defective gene for dystrophin (A
type of protein in muscles).
Incidence = 1 in 3,600 male infants
Usually appear before age 6 and may appear as
early as infancy.
Learning difficulties (IQ can be below 75)
Begins in the legs and pelvis less severe in the arms,
neck, and other areas of the body
Problems with motor skills (running, hopping, jumping)
Trouble getting up from a lying position or climbing stairs
Weakness quickly gets worse
Progressive difficulty walking:
Ability to walk may be lost by age 12
Breathing difficulties and heart disease usually start
by age 20
Blood fails to clot normally
Lacking a blood clotting factor VIII
(antihemophilic globulin, AHG), IX (Chrismas
Bleeding from even minor cuts
Incidence = 1,500 newborn males.
Hemophilia A = Lack of clotting factor VIII.
Hemophilia B = "Christmas Disease" is a
defect in clotting factor IX.
Transfusions of fresh whole blood or plasma
or factor to control bleeding
Also known as Martin-Bell syndrome; Marker X
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. (*More repeats, the
more likely there is to be a problem.)
Male and female can both be affected.
Male have only one X chromosome, single fragile
X more likely to affect them more severely.
Family history of fragile X syndrome,
especially a male relative
Large testicles (macro-orchidism)
Tendency to avoid eye contact
Large forehead and/or ears with a prominent
Aneuploidy = Addition or loss of one (rarely two)
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
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