Slide 1

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

Slide 2

Down Syndrome ( Trisomy 21 ) is a chromosomal abnormality characterized by the presence of an extra genetic material on the 21 st 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.

Slide 3

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.

Slide 4

Karyotype of Trisomy 21

Slide 5

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

Slide 6

Mental retardation is the overriding feature of Downs syndrome. Most people with Downs 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.

Slide 7

Patients with Downs 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.

Slide 8

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 Alzheimers disease. ( patients older than 40 ) e. abnormal immune responses that predispose them to serious infections, particularly of the lungs and to thyroid autoimmunity.

Slide 9

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.

Slide 10

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

Slide 11

Children with the syndrome may also have behavior problems such as obsession, compulsion, stubbornness, and temper tantrums. occurs in approximately one of every 12,000- 15,000 people, in both boys and girls

Slide 12

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.".

Slide 13

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.

Slide 14

Cri du chat syndrome also known as chromosome 5p deletion syndrome, 5p minus syndrome or Lejeunes 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.

Slide 15

Slide 16

Slide 17

first described by Jrme 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.

Slide 18

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.

Slide 19

behavioral problems such as hyperactivity, aggression, tantrums, and repetitive movements. unusual facial features which may change over time. excessive dribbling constipation.

Slide 20

Other common findings: hypotonia, microcephaly, growth retardation, a round face with full cheeks, hypertelorism, epicanthal folds, down-slanting palpebral fissures, strabismus, flat nasal bridge, down- turned 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.

Slide 21

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.

Slide 22

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 randomly- occurring, 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.

Slide 23

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.

Slide 24

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

Slide 25

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.

Slide 26

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

Slide 27

The childs 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.

Slide 28

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.

Slide 29

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.

Slide 30

EDWARDS SYNDROME Trisomy 18 presence of all or part of an extra 18 th 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

Slide 31

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

Slide 32

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

Slide 33

TRISOMY 9 having three copies (trisomy) of chromosome number 9 appppear with or without mossaicism with long survival rate

Slide 34

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.

Slide 35

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

Slide 36

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

Slide 37

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.

Slide 38

Karyotype of trisomy 13

Slide 39

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)

Slide 40

Extra fingers or toes (polydactyl) Hernias: umbilical hernia, inguinal hernia Scalp defects (absent skin)

Slide 41

Small eyes Small head (microcephaly) Small lower jaw (micrognathia) Low-set ears Mental retardation Decreased muscle tone

Slide 42

Slide 43

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

Slide 44

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.

Slide 45

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.