Download Down Syndrome ( Trisomy 21 )

Psychosis due to genetics
Presented by:
Agbisit, Queenie
Balao, Sylvester
Barrameda, Yasmin
Beguia, Andriza Mae
Biliran, Joyce Venus
Bognot, Mary Astrid
Bueno, Chrisnabelle-Liza
Calamigan, Scheibel Kates
Calbay, Hazel Ellenore
Calingasan, Cristine
Castro, Lou Sandino
Corpuz, Grace
Down Syndrome ( Trisomy 21 )
 is a chromosomal abnormality characterized by the
presence of an extra genetic material on the 21st
chromosome which causes delays in the way a child
develop , both physically and mentally.
 it is the most common of the chromosomal disorders and
is the major cause of mental retardation.
 it is named after John Langdon Down , the British doctor
who described the syndrome in 1866.
What causes it?
 In most cases of down syndrome
a child gets an extra chromosome 21
for a total of 47 chromosome instead
of 46.
 Women at age 35 and older have a
significant higher risk of having a
child with the condition.
 Down syndrome occurs in 1 in 800
births.
Karyotype of Trisomy 21
 People with Down Syndrome tend to show certain physical
factors such as:
a. Flat facial profile
b. Oblique eye fissures with epicanthic
folds on the inner corner of the eye
c. White spots on the iris ( Brushfield spots )
d. Abnormally shaped ears
e. Protruding tongue
f. Single palmar transversal crease
g. Muscle hypotonia
h. Small hands and feet
 Mental retardation is the overriding feature of
Down’s syndrome.
 Most people with Down’s syndrome have IQs that
fall in the mild to moderate range of mental
retardation.
 Approximately 80% of those afflicted have an IQ of
25 to 50.
 They may have delayed language development and
slow motor development.
Patients with Down’s syndrome are placid,
cheerful and cooperative which facilitates their
adjustment at home.
However, those seems to change in adolescents,
especially those in institutions, who may develop
various emotional difficulties, behavior
disorders, and ( rarely ) psychotic illness.
 There are a variety of other health conditions that
are often seen in people who have Down syndrome,
including:
a. congenital heart disease
b. hearing problems
c. atresias of the esophagus and small bowel
d. neuropathologic changes characteristic of
Alzheimer’s disease. ( patients older than 40 )
e. abnormal immune responses that predispose
them
to serious infections, particularly of the lungs and
to thyroid autoimmunity.
 With the advent of antibiotics few young patients
succumb to infections, but most of them do not live
beyond the age of 40.
 Despite all these problems, improved medical care
has increased the longevity of individuals with
trisomy 21.
 No treatment has proved effective.
Prader-Willi
 Prader-Willi syndrome is an autosomal dominant
disorder characterized by mild to moderate mental
retardation or learning problems, short stature,
hypotonia, obesity, small hands and feet, and
hypogonadism.
 In 65% to 70% of cases, an interstitial deletion of band
q12 in the long arm of chromosome 15,
del(15)(q11.2q13), can be detected.
 in all cases the deletion affects the paternally-derived
chromosome 15
 Children with the syndrome may also have
behavior problems such as obsession,
compulsion, stubbornness, and temper
tantrums.
 occurs in approximately one of every 12,00015,000 people, in both boys and girls
Angelman syndrome
 Patients with the phenotypically distinct
Angelman syndrome are born with a deletion of
the same chromosomal region as Prader-Willi
but derived it from their mothers.
 Patients are also mentally retarded, but in
addition they present with ataxic gait, seizures,
and inappropriate laughter and excitability.
 Because of their laughter and ataxia, they are
also called "happy puppets.".
 Mental retardation is first noted at around six
months of age; however, the unique clinical
features of AS do not manifest until after one
year of age, and it can take several years
before the correct clinical diagnosis is obvious.
Cri du chat syndrome
 also known as
 chromosome 5p deletion syndrome,
 5p minus syndrome or
 Lejeune’s syndrome
is a rare genetic disorder due to a missing part of
chromosome 5.
 French term (cat-cry or call of the cat) referring to
the characteristic cat-like cry of affected children.
 first described by Jérôme Lejeune in 1963
 affects an estimated 1 in 20,000 to 50,000 live
births, strikes all ethnicities, and is more common in
females by a 4:3 ratio.
Signs & Symptoms
 The syndrome gets its name from the characteristic
cry of affected infants, which is similar to that of a
meowing kitten, due to problems with the larynx
and nervous system. About 1/3 of children lose the cry
by age 2.
 Other symptoms:
 feeding problems because of difficulty
swallowing and sucking.
 Low birth weight and poor growth.
 behavioral problems such as hyperactivity,
aggression, tantrums, and repetitive movements.
 unusual facial features which may change over time.
 excessive dribbling
 constipation.
 Other common findings:
 hypotonia, microcephaly, growth retardation,
a round face with full cheeks, hypertelorism,
epicanthal folds, down-slanting palpebral
fissures, strabismus, flat nasal bridge, downturned mouth, micrognathia, low-set ears,
short fingers, single palmar creases and
cardiac defects (eg. VSD, ASD, PDA,TOF).
 People with Cri du chat are fertile and can
reproduce.
 Late childhood and adolescent findings:
 significant intellectual disability,
 microcephaly,
 coarsening of facial features,
 prominent supraorbital ridges,
 deep-set eyes, hypoplastic nasal bridge,
 severe malocclusion, and scoliosis.

Affected females reach puberty, develop secondary
sex characteristics, and menstruate at the usual time.
The genital tract is usually normal in females except
for a report of a bicornuate uterus. In males, testes are
often small, but spermatogenesis is thought to be
normal.
Genetics
 due to a partial deletion of the short arm of
chromosome number 5, also called "5p monosomy".
 90% of cases results from a sporadic, or randomlyoccurring, de novo deletion.
 10-15% are due to unequal segregation of a parental
balanced translocation where the 5p monosomy is
often accompanied by a trisomic portion of the
genome.
 Loss of a small region in band 5p15.2 (cri du chat
critical region) correlates with all the clinical features
of the syndrome with the exception of the catlike cry
band 5p15.3 (catlike critical region)
 2 noncontiguous critical regions contain genes
involved in this condition's etiology
Semaphorine F (SEMA5A) and
 Delta catenin (CTNND2)

are potentially involved in cerebral development.
 telomerase reverse transcriptase(hTERT)
gene ( 5p15.33) may contribute to the phenotypic
changes in cri du chat syndrome as well.
Common Behavioural Difficulties
 Concentration difficulties and hyperactivity.
 Self-injurious and compulsive behaviour:
 self-biting, skin picking, hitting head with hand,
and hitting head against objects.
 Three main theories
1. Neurotransmitters (dopamine, serotonin and
the endorphins)
2. Response to pain and discomfort
3. Learned behaviour
 Stereotyped behaviour
Fragile X syndrome
 Is the prototype of diseases in which the mutation is
characterized by a long repeating sequence of
three nucleotides, in most cases the affected
sequences share the nucleotides guanine and
cytosine.
 With a frequency of 1 in 1500 for affected males
and 1 in 8000 for affected females, fragile-X
syndrome is the second most common genetic cause
of mental retardation, after Down syndrome.
 It is an X-linked disorder characterized by an
inducible cytogenetic abnormality in the X
chromosome and an unusual mutation within the
familial mental retardation – 1 (FMR1) gene. The
fragile site on the X chromosome is expressed when
cells are cultured in a folate-poor medium.
Characteristic physical phenotype
 Long face with large mandible
 Large everted ears
 Large testicles (macroorchidism)
 Small stature
 Mimic connective tissue disorder:
 Hyperextensible joints
 High arched palate
 Mitral valve prolapse
 The child’s intellectual level ranges from low
average to severely retarded. Many children
have symptoms of attention-deficit
hyperactivity disorder and specific
developmental disorders.
 Female carriers are usually less impaired than
males with fragile X, but female carriers can
manifest the typical physical characteristics
and can be mildly retarded.
Pattern of Transmission
 Carrier Males: Approximately 20% of males who, by
pedigree analysis and by molecular tests, are known
to carry a fragile-X mutation are clinically and
cytogenetically normal.
 Affected females: 30% to 50% of carrier females are
affected (ex: mentally retarded), a number much
higher than that in other X-linked recessive disorder.
 Risk of phenotypic effects: Risk depends on the
position of the individual in the pedigree. For
example, brothers of transmitting males are at a 9%
risk of having mental retardation, whereas
grandsons of transmitting males incur a 40% risk.
Diagnosis
 Although demonstration of an abnormal
karyotype led to the identification of this
disorder, PCR-based detection of the repeats is
now the method of choice for diagnosis.
 With Southern blot analysis, distinction
between premutations and mutations can be
made prenatally as well as postnatally.
EDWARDS SYNDROME
 Trisomy 18
 presence of all or part of an extra 18th chromosome
 second most common autosomal trisomy
 incidence increases as the mother's age increasesi
 has a very low rate of survival, resulting from heart
abnormalities, kidney malformations, and other
internal organ disorders very low rate
 more prevalent in females
 caused by a meiotic nondisjunction event
EDWARDS SYNDROME
FEATURES:
 kidney malformations
 structural heart defects at birth (ventricular septal
defect, atrial septal defect, patent ductus arteriosus)
 Omphalocele
 esophageal atresia
 mental retardation
 developmental delays
 growth deficiency
 feeding difficulties
 breathing difficulties and arthrogryposis
 Microcephaly with occiput
 low-set, malformed ears
 Micrognathia
 cleft lip/cleft palate
 upturned nose
 narrow eyelid folds (palpebral fissures)
 ocular hypertelorism
 Ptosis
 short breast bone
 clenched hands, underdeveloped thumbs and or
nails, absent radius, webbing of the second and third
toes, clubfoot or Rocker bottom feet
 undescended testicles in males
TRISOMY 9
 having three copies (trisomy) of chromosome
number 9 appppear with or without mossaicism
 with long survival rate
FEATURES:
 Dysmorphisms in the
skull, nervous system,
 mental retardation
 Dysmorphisms in the
heart, kidneys, and
musculoskeletal system
 a small face
 wide fontanelle
 prominent occiput
 Micrognathia
 low set ears
 upslanting palpebral
fissures
 high arched palate
 short sternum
 overlapping fingers
 limited hip abduction
 rocker bottom feet
 heart murmurs
 webbed neck.
WARKANY SYNDROME
 trisomy 8
 Chromosomal aberration that has severe effects on
the fetus
 also found in some cases of chronic myeloid
leukaemia
 result of karyotypic instability caused by the bcr:abl
fusion gene
FEATURES:
 retarded psychomotor development
 moderate to severe mental retardation
 variable growth patterns (either abnormally short or
tall stature)
 an expressionless face
 many musculoskeletal, visceral, and eye
abnormalities and anomalies
PATAU SYNDROME
 also known as trisomy 13 and trisomy D
 is a chromosomal abnormality in which a patient has
an additional chromosome 13 due to a
nondisjunction of chromosomes during meiosis.
Karyotype of trisomy 13
Manifestations and physical findings
 Cleft lip or palate
 Close-set eyes -- eyes
may actually fuse
together into one
 Hole, split, or cleft in the
iris (coloboma)
 Extra fingers or toes
(polydactyl)
 Hernias: umbilical
hernia, inguinal hernia
 Scalp defects (absent
skin)
 Small eyes
 Small head
(microcephaly)
 Small lower jaw
(micrognathia)
 Low-set ears
 Mental retardation
 Decreased muscle tone
Possible Complications:
Complications begin almost immediately. Congenital heart
disease is present in approximately 80% of infants with
Trisomy 13. Complications may include:
Breathing difficulty or lack of breathing (apnea)
 Deafness
 Feeding problems
 Heart failure
 Seizures
 Vision problems

Treatment:
 Treatment of Patau syndrome focuses on the
particular physical problems with which each child is
born.
 Surgery may be necessary to repair heart defects or
cleft lip and cleft palate.
 Physical, occupational, and speech therapy will help
individuals with Patau syndrome reach their full
developmental potential.
Prevention:
 Trisomy 13 can be diagnosed prenatally by
amniocentesis with chromosome studies of the
amniotic cells.
 Parents of infants with trisomy 13 caused by a
translocation should have genetic testing and
counseling, which may help them prevent
recurrence.