Down syndrome

Down syndrome or trisomy 21 is a genetic disorder caused by the

presence of all or part of an extra 21st chromosome. It is named after
John Langdon Down, the British doctor who first described it in 1866.
The condition is characterized by a combination of major and minor
differences in body structure. Often Down syndrome is associated with
some impairment of cognitive ability and physical growth as well as
facial appearance. Down syndrome is usually identified at birth.
 Effects
 Individuals with Down syndrome may have some or all of
the following physical characteristics: oblique eye fissures
with epicanthic skin folds on the inner corner of the eyes,
muscle hypotonia (poor muscle tone), a flat nasal bridge, a
single palmar fold (also known as a simian crease), a
protruding tongue (due to small oral cavity, and an
enlarged tongue near the tonsils), a short neck, white spots
on the iris known as Brushfield spots, excessive flexibility in
joints, congenital heart defects, excessive space between
large toe and second toe, a single flexion furrow of the fifth
finger, and a higher number of ulnar loop dermatoglyphs.
Most individuals with Down syndrome have
mental retardation in the mild (IQ 50–70) to moderate (IQ
35–50) range, with scores of children having Mosaic Down
syndrome (explained below) typically 10–30 points higher.
In addition, individuals with Down syndrome can have
serious abnormalities affecting any body system.
 Genetics

 Down syndrome is a chromosomal abnormality

characterized by the presence of an extra copy of
genetic material on the 21st chromosome, either
in whole (trisomy 21) or part (such as due to
translocations).
 Klinefelter's syndrome

• Klinefelter's syndrome, 47,XXY or XXY

syndrome is a condition caused by a
chromosome nondisjunction in males; affected
individuals have a pair of X sex chromosomes
instead of just one and are at additional risk for
some medical conditions. It is named after Dr.
Harry Klinefelter, a medical researcher at
Massachusetts General Hospital,
Boston, Massachusetts, who first described this
condition in 1942. The condition exists in roughly
1 out of every 500 males.
Signs and symptoms

• Affected males are almost always sterile, and some degree

of language impairment may be present. In adults, possible
characteristics vary widely and include little to no signs of
affectedness, a lanky, youthful build and facial appearance,
or a rounded body type with some degree of gynecomastia
(increased breast tissue). Gynecomastia to some extent is
present in about a third of individuals affected, a higher
percentage than in the XY population. The far end of the
spectrum is also associated with an increased risk of
breast cancer, pulmonary disease, varicose veins,
diabetes mellitus, rheumatoid arthritis, and osteoporosis,
risks shared with women.
• Rare X-linked recessive problems occur even more
infrequently in XXY males, since these conditions are
transmitted by genes on the X chromosome, and people
with two X chromosomes are typically carriers rather than
affected
Cause

• The XXY chromosome arrangement is one of the

most common genetic variations from the XY
karyotype, occurring in about 1 in 500 live male
births. Because of the extra chromosome,
individuals with the condition are usually referred
to as "XXY Males", or "47,XXY Males" rather than
as "suffering from Klinefelter's syndrome."
 Leber' s he redi tary op tic
neuropathy

• Le be r’s he redi tar y op tic ne urop athy (LH ON) or

Le be r op tic at roph y is a mitochondrially inherited
(mother to all offspring) degeneration of retinal
ganglion cells (RGCs) and their axons that leads to an
acute or subacute loss of central vision; this affects
predominantly young adult males. However, LHON is only
transmitted through the mother as it is primarily due to
mutations in the mitochondrial (not nuclear) genome and
only the egg contributes mitochondria to the embryo.
LHON is usually due to one of three pathogenic
mitochondrial DNA (mtDNA) point mutations. These
mutations affect nucleotide positions 11778, 3460 and
14484, respectively in the ND4, ND1 and ND6 subunit
genes of complex I of the oxidative phosphorylation
chain in mitochondria. Men cannot pass on the disease to
their offspring
Figure
 Signs & symptoms
• Clinically, there is an acute onset of visual loss,
first in one, eye and then a few weeks later in the
other. This eventually evolves to very severe optic
atrophy and permanent decrease of visual acuity. In
the acute stage lasting a few weeks, the affected
eye demonstrates an edematous appearance of the
nerve fiber layer especially in the arcuate bundles
and enlarged or telangectatic and tortuous
peripapillary vessels (microangiopathy). These
main features are seen on, fundus examination just
before or subsequent to the onset of visual loss.
Examination reveals decreased visual acuity, loss
of color vision and a cecocentral scotoma on
visual field examination.
 Genetic s

• Leber hereditary optic neuropathy is a

condition related to changes in
mitochondrial DNA. Although most DNA is
packaged in chromosomes within the
nucleus, mitochondria have a distinct
mitochondrial genome composed of mtDNA
 Muscular dystrophy
Muscular dystrophy is a genetic condition that
describes more than 30 genetic and hereditary
muscle diseases. Of these 30, nine types are
formally declared to be Muscular Dystrophy and
the remaining are generally classified as muscular
dystrophy. Muscular Dystrophy is characterized by
progressive skeletal muscle weakness, defects in
muscle proteins, and the death of muscle cells and
tissue . In some forms of muscular dystrophy,
cardiac and smooth muscles are affected.
Muscular dystrophy is the most well known of
hereditary diseases
 Genetic cause

These conditions are inherited, and the different muscular

dystrophies follow various inheritance patterns.
The most well-known type, Duchenne muscular dystrophy
(DMD), is inherited in an X-linked recessive pattern, meaning
that the mutated gene that causes the disorder is located on
the X chromosome, one of the two sex chromosomes, and is
thus considered sex-linked. In males (who have only one X
chromosome) one altered copy of the gene in each cell is
sufficient to cause the condition. In females (who have two X
chromosomes) a mutation must generally be present in both
copies of the gene to cause the disorder (relatively rare
exceptions, manifesting carriers, do occur due to
dosage compensation/X-inactivation). Males are therefore
affected by X-linked recessive disorders much more often
than females. A characteristic of X-linked inheritance is that
fathers cannot pass X-linked traits to their sons.
 Symptoms

Principal symptoms include but are not limited to:

Progressive Muscle Wasting
Weakness
Loss of Function in Muscle Skills
Poor Balance
Frequent Falls
Walking Difficulty
Waddling Gait
Calf Pain
Limited Range of Movement
Joint Contractures
Cataracts
Frontal Baldness
Drooping Eyelids (ptosis)
Drooling
Gonadal Atrophy
Mental Impairment (with myotonic dystrophy)
Scoliosis (curved spine
Diagnosis

The diagnosis of muscular dystrophy is based on

the results of a muscle biopsy. In some cases, a
DNA blood test may be all that is needed.
A physical examination and the patient's medical
history will help the doctor determine the type of
muscular dystrophy. Specific muscle groups are
affected by different types of muscular dystrophy.
 Treatment
There is no known cure for muscular dystrophy.
Inactivity (such as bed-rest and even sitting for
long periods) can worsen the disease.
Physical therapy and orthopedic instruments (e.g.,
wheelchairs, standing frames) may be helpful
 Tay-Sachs disease
 Tay-Sachs disease (abbreviated TSD, also
known as "GM2 gangliosidosis") is a
genetic disorder, fatal in its most common variant
known as Infantile Tay-Sachs disease. TSD is
inherited in an autosomal recessive pattern. The
disease occurs when harmful quantities of a
fatty acid derivative called a ganglioside
accumulate in the nerve cells of the brain.
Gangliosides are lipids, components of cellular
membranes, and the ganglioside GM2, implicated
in Tay-Sachs disease, is especially common in the
nervous tissue of the brain.
 The disease is named after the British
ophthalmologist Warren Tay who first
described the red spot on the retina of the
eye in 1881
 Spinal muscular atrophy
 Spinal Muscular Atrophy (SMA) is a term
applied to a number of different disorders, all
having in common a genetic cause and the
manifestation of weakness due to loss of the
motor neurons of the spinal cord and brainstem
 Symptoms

 Infantile SMA is the most severe form. Some of

the symptoms include:
 muscle weakness
 poor muscle tone
 weak cry
 limpness
 difficulty swallowing
 the legs tend to be weaker than the arms
 feeding difficulties
 increased susceptibility to
respiratory tract infections
 developmental milestones, such as lifting the
head or sitting up, can't be reached
 Cause

 The region of chromosome 5 that contains the SMN

(Survival Motor Neuron) gene has a large duplication. A
large sequence that contains several genes occurs twice in
adjacent segments. There are thus two copies of the gene,
SMN1 and SMN2. The SMN2 gene has an additional
mutation that makes it less efficient at making protein,
though it does so in a low level. SMA is caused by loss of
the SMN1 gene from both chromosomes. The severity of
SMA, ranging from SMA 1 to SMA 3, is partly related to how
well the remaining SMN 2 genes can make up for the loss of
SMN 1. Often there are additional copies of SMN2, and an
increasing number of SMN2 copies causes less severe
disease.
 All forms of SMN-associated SMA have a combined
incidence of about 1 in 6,000. SMA is the most common
cause of genetically determined neonatal death. The gene
frequency is thus around 1:80, and approximately one in 40
persons are carriers. There are no known health
consequences of being a carrier, and the only way one
might know to consider the possibility is if a relative is
affected