Transcript Trisomy 18 • Incidence 1:3333 live births • Most common

Simple and Complex Genetic
Diseases
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Simple: One gene -> one disease
Example: sickle-cell anemia
Complex: Many genes interacting with
other and the environment -> one
disease
Examples: MS, Types I, II diabetes
Single Gene Disorders
Autosomal recessive
 Albinism
 Cystic fibrosis
 Phenylketonurea
Galactosemia
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Metabolic disorder defect in galactose meatbolism,
The problem in the enzyme galactose 1- phoshate
uridyl transferese, Which breakdown glucose.
This leads to accumulation of galactose in blood,
leads to blood poisoning which cause:
1- Hepatomegaly
2- Cirrrhosis
3- Renal failure
4- Cataracts
5- Brain damage
Mucopolysaccharidosis
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Absence of lysosomal enzymes (α-Liduronidase) which digest
Mucopolysaccharide (also named
Glycosaminoglycans)
This sugar is found in the liquid
between joints and act as lubricant.
Autosomal dominant
Achondroplasia
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Askeletal disorder causeing dwarfism,
shortening in limbs and digits,
enlargement in skull.
Caused as a defect in Fibroblast Growth
factor Receptor Gene3 (FGFR3)
This leads to a defect in cartilage and
bone growth.
Marfan syndrome
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15q 15-21
Affect c.t
Defect in FBN1 gene
Neurofibromatosis
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17q11
Swallow sacs under skin affect skin,
bone and nerves
Caused as a defect in the Neurofibromin
gene.
Brachydactyly
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5p13 and 2q33
Problem in fingers
Noonan syndrome
Defect in PTPN11 gene which encode
Protain Tyrosine Phosphatase, which
play a role in embryonic development,
Differentiation and migration
Huntington's disease
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4p16
Trinucleotide repeat expansion in the
gene which encode Huntington protein.
This leads to defect in the produced
protein, degeneration in neurons, and
chorea.
1 Glucose-6-ph. Dehydrogenase deficiency
X-Linked r
 Deficiency in
 Glucose-6-ph. dehydrogenase enzyme
( G6PDH)
 This enzyme is related to Pentose
phosphorylation Pathway
 This enzyme converts Glucose-6-ph to
6- Phosphogluconate delta-lactone
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Duchenne muscular dystrophy
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Defect in the gene which encode
Dystrophin
Haemophilia A
Defect in the gene which encode Factor
VIII
Hypophosphatemia
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X-linked dominant disorders
a form of vitamin D- resistant rickets
Y-linked genes
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Sex determining gene (SRY) encodes SDF
which important in sex determination by
playing a role in early stages of testis
differentiation.
Any defect cause XY female (Swyer
syndrome)
Translocation of part Y chromosome which
contain SRY gene to X chromosome give XX
male syndrome
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ANT3 (adenine nucleotide translocase)
Produce enzyme change and transfer
ADP from internal mitochondria to
ouside as ATP
CSF2RA
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Colony stimulating factor 2
receptor α
Produce cell surface receptor for growth
factor
Control production, differentiation of
granulocytes and macrophages.
H-Y gene
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Plasma membrane protein
Play a role in testis differentiation
ZFY
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Zinc finger protein
DNA binding protein that regulate gene
expression
Mitochondrial disorders
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Mitochondrial myopathy
neurodegenerative disorder
seizures, diabetes mellitus, hearing loss,
short stature, and exercise intolerance
are clearly part of the disorder.
MERRF syndrome
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muscular disorders
cause a dysfunction of the brain and
muscles (encephalomyopathies).
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The most characteristic symptom of MERRF
syndrome is seizures that are usually sudden,
brief, jerking, spasms that can affect the
limbs or the entire body.
Impairment of the ability to coordinate
movements (ataxia), as well as an abnormal
accumulation of lactic acid in the blood (lactic
acidosis) may also be present in affected
individuals.
Difficulty speaking (dysarthria), optic atrophy,
short stature, hearing loss, and involuntary
jerking of the eyes (nystagmus)
Leigh syndrome
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progressive neurodegenerative disorder in
one or more areas of the central nervous
system, including the brainstem, thalamus,
basal ganglia, cerebellum, and spinal cord.
The lesions are areas of demyelination,
gliosis, necrosis, spongiosis, or capillary
proliferation. Clinical symptoms depend on
which areas of the central nervous system are
involved.
The most common underlying cause is a
defect in oxidative phosphorylation
Sideroblastic anemia
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abnormal production of RBCs which can evolve into
leukemia.
Thus, the body has iron available, but cannot
incorporate it into hemoglobin
The common feature of these causes is a failure to
completely form heme- whose biosynthesis takes
place partly in the mitochondria. This leads to
deposits of iron in the mitochondria that form a ring
around the nucleus of the developing RBCs. This
leads to a stage in bone marrow disorder that leads
to acute leukemia.
Myoclonus
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involuntary twitching of muscles.
The myoclonic twitches or jerks are usually
caused by sudden muscle contractions;
Contractions are called positive myoclonus;
relaxations are called negative myoclonus.
myoclonic jerks are also a sign of a number
of neurological disorders.
Hiccups are also a kind of myoclonic jerk
specifically affecting the diaphragum.
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myoclonus is one of several signs in a
wide variety of nervous system
disorders such as Parkinson’s disease,
Alzheimer’s disease, and some forms of
epilepsy
Myopathies
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affect muscles connected to bones
(called skeletal muscles), such as the
biceps in the upper arm and the
quadriceps in the thigh.
Myopathies can be caused by inherited
genetic defects (e.g., muscular
dystrophies), and endocrine,
inflammatory , and metabolic disorders.
Cardiomyopathy
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the heart muscle becomes inflamed and doesn't work
as well as it should.
There may be multiple causes including viral
infections.
Cardiomyopathy can be classified as primary or
secondary.
Primary cardiomyopathy can't be attributed to a
specific cause, such as high blood pressure, heart
valve disease, artery diseases or congenital heart
defects.
Secondary cardiomyopathy is due to specific causes.
It's often associated with diseases involving other
organs as well as the heart.
Renal tubular acidosis (RTA)
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is a disease that occurs when the kidneys fail to
excrete acids into the urine, which causes a person's
blood to remain too acidic.
Without proper treatment, chronic acidity of the
blood leads to growth retardation, kidney stones,
bone disease, and progressive renal failure.
The word acidosis refers to the tendency for RTA to
lower the blood's pH. When the blood pH is below
normal (7.35), this is called acidemia.
Its causes are diverse, and its consequences can be
serious, including coma and death.
Variation in chromosome number
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Trisomy 18 (47,XY,+18) – Edward
Syndrome
Trisomy 18
•Incidence 1:3333 live births
•Most common abnormality in stillbirths
with multiple
congenital abnormalities
•Prenatal growth deficiency resulting in
a small for gestational
age infant (SGA)
• %90congenital heart defect VSD
%10 •alive at one year
•Marked developmental disability
Trisomy 18 -Physical Features
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•Prominent occiput
•Micrognathia
•Microcephaly
•Low set malformed ears
•Characteristic clenched fists
•Rocker-bottom feet
•Short big toe that is dorsiflexed
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Trisomy 18 –Edward Syndrome
Trisomy 18
• Prominent Occiput
• Low-set malformed ears
• Small chin
• Clenched fists
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Trisomy 18
•Ocular manifestations in 10%
•Low-arch dermal ridge pattern
•Underdeveloped nails
•Congenital anomalies of lungs,diaphragm,
and
kidneys
•Hernias, cryptorchidism, rectus muscle
separation
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Trisomy 13 (47,XY,+13) – Patau
Syndrome
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Trisomy 13
•Incidence 1:5,000 births
•Distinctive malformation pattern
(Craniofacial and Central Nervous
System)
%95 •spontaneously aborted
•Survival rate and development similar
to Trisomy 18
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Trisomy 13 PatauSyndrome
•Microcephalywith sloping forehead
•Holoprosencephaly
•Ophthalmologic abnormalities
microphthalmiaor anophthalmia
Colobomataof iris and ciliarybody
•Cleft lip +/-palate
•Low set ears with abnormal helices
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Trisomy 13 PatauSyndrome
•Cardiac defects: ASD, PDA, VSD
•Males: cryptorchidism ; Females:
Bicornuateuterus
•Polycystic kidneys
•Aplasiacutis congenita
•Polydactylyof hands +/-feet
•Rockerbottomfeet
Turner syndrome
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SHORT STATURE
OVARIAN DYSGENESIS
INFERTILITY
LEARNING DISABILITIES
SPATIAL PERCEPTION
XXX females
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About one woman in 1000 has an extra X
chromosome. It
seems to do little harm, individuals are fertile
and do not
transmit the extra chromosome.
XYY males
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XYY males Incidence 1 in 1000 male
births.
May be without any symptoms. Males
are tall but normally proportioned.
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Glu
Ab 5i GTG CAC CTG ACT CCT GAG
GAG AAG TCT O O O 3i
Sb 5i GTG CAC CTG ACT CCT GTG
GAG AAG TCT O O O 3i
Val