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TRISOMY 21- TRISOMY 21- DOWN DOWN SYNDROME SYNDROME Dr. Rubzzz Dr. Rubzzz

Down syndrome by Dr. Rubzzz

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Page 1: Down syndrome by Dr. Rubzzz

TRISOMY 21-

TRISOMY 21-

DOWN DOWN

SYNDROMESYNDROME

Dr. RubzzzDr. Rubzzz

Page 2: Down syndrome by Dr. Rubzzz

John Langdon John Langdon DownDown

1828-18961828-1896

• He trained at the He trained at the London Hospital.London Hospital.

• He was the first to He was the first to recognize what he recognize what he called called “Mongolian “Mongolian

idiocyidiocy” as a ” as a syndrome, a syndrome, a

“throwback” to a “throwback” to a “lower” race.“lower” race.

• The children The children appeared similar, like appeared similar, like brothers and sisters.brothers and sisters.

• The disorder became The disorder became known as known as

““MongolismMongolism.”.”

• It is now calledIt is now called Down Down syndrome.syndrome.

• He opposed slavery, He opposed slavery, and argued this “ and argued this “

throwback” throwback”

• disproved the disproved the “Negroid race” was “Negroid race” was

inferior. inferior.

• He advocated equal He advocated equal education for women.education for women.

Page 3: Down syndrome by Dr. Rubzzz

IncidenceIncidence

Approximately one in 800-

Approximately one in 800-

1000 live births.

1000 live births.

Page 4: Down syndrome by Dr. Rubzzz

Table 1: Incidence of Down Syndrome

Age (years) Incidence

20 1 in 1500

30 1 in 900

35 1 in 350

40 1 in 100

41 1 in 70

42 1 in 55

43 1 in 40

44 1 in 30

45 1 in 25

Maternal Age- Specific Risk for Trisomy -21 at livebirth

Page 5: Down syndrome by Dr. Rubzzz

Geneti

csG

eneti

cs

Trisomy 21 (47, +21), -

Trisomy 21 (47, +21), -

95 %, The frequency of

95 %, The frequency of

trisomy increases with

trisomy increases with

increasing maternal

increasing maternal

age.age. Robertsonian

Robertsonian translocation involving

translocation involving

chromosome 21-

chromosome 21- Approx. 3 %, not

Approx. 3 %, not related to maternal

related to maternal age.age. Trisomy 21 mosaicism –

Trisomy 21 mosaicism –

2 % cases2 % cases

Page 6: Down syndrome by Dr. Rubzzz

Table 2. Karyotyping in Down syndrome

Recurrence Risk by Karyotype

Non-disjunction trisomy 21

Robertsonian Translocation

3%

Mosaicism 2%

Nondisjunction Trisomy

47(XX or XY) + 21 1%

Translocation on

both parents normal <1%

other carrier 10%

father carrier 2.5%

either parent t(21q;21q) 100%

Mosaics <1%

Page 7: Down syndrome by Dr. Rubzzz
Page 8: Down syndrome by Dr. Rubzzz
Page 9: Down syndrome by Dr. Rubzzz

24,X +21

23,Y

47,XY,+21

Egg,extra 21

Sperm, normal

Zygote

Trisomy 21 in Down Syndrome

Page 10: Down syndrome by Dr. Rubzzz
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Page 12: Down syndrome by Dr. Rubzzz

Clinical FeaturesClinical Features

Head and neckHead and neck BrachycephalyBrachycephaly Up-slanting palpebral Up-slanting palpebral

fissuresfissures Epicanthal foldsEpicanthal folds Brushfield spotsBrushfield spots Flat nasal bridgeFlat nasal bridge Folded or dysplastic earsFolded or dysplastic ears Open mouthOpen mouth Protruding tongueProtruding tongue Short neck Short neck Excessive skin at the Excessive skin at the

nape of necknape of neck

ExtremitiesExtremities ShortShort broad handsbroad hands

Short fifth fingerShort fifth finger

Incurved fifth fingerIncurved fifth finger

Transverse palmer creaseTransverse palmer crease

Space between first and Space between first and second toesecond toe

Hyper flexibility of jointsHyper flexibility of joints

Life expectancy : 55 years (National Down Syndrome Society)

Page 13: Down syndrome by Dr. Rubzzz
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Page 15: Down syndrome by Dr. Rubzzz

Neonata

l N

eonata

l

featu

res

featu

res

Flat facial profileFlat facial profile Poor Moro reflexPoor Moro reflex Excessive skin at Excessive skin at

the nape of neckthe nape of neck Slanted palpebral Slanted palpebral

fissuresfissuresHypotonia Hypotonia Hyper flexibility Hyper flexibility

of jointsof joints

Dysplasia of Dysplasia of pelvispelvis

Anomalous earsAnomalous ears

Dysplasia of Dysplasia of midphalanx of midphalanx of fifth fingerfifth finger

Transverse Transverse palmer creasepalmer crease

Page 16: Down syndrome by Dr. Rubzzz

Medical Problem

Page 17: Down syndrome by Dr. Rubzzz

Newborn

• cardiac defects (50% ): AVSD [most common], VSD, ASD, TOF or PDA• gastrointestinal (12%): duodenal atresia [commonest], tracheo-oesophagealfistula, anorectal malformation, pyloric stenosis and Hirshsprung disease.• vision: congenital cataracts (3%), glaucoma.• hypotonia & joint laxity• feeding problems. UsuallyResolve in few weeks.• congenital hypothyroidism (1%)• congenital dislocation of the hips

Page 18: Down syndrome by Dr. Rubzzz

Infancy and Childhood

• delayed developmental milestones• mild to moderate intellectualimpairment (IQ 25 to 50)• seizure disorder (6%)• recurrent respiratory infections• hearing loss (>60%) due to secretory otitis media, sensorineural deafness,or both• visual Impairment – squint (50%), cataract (3%), nystagmus (35%), glaucoma,refractive errors (70%)• sleep related upper airway obstruction. Often multiple factorial.• leukaemia (relative risk:15 to 20 times). Incidence 1%

Page 19: Down syndrome by Dr. Rubzzz

• atlantoaxial instability. Symptoms of spinal cord compression include neck pain,change in gait, unusual posturing of the head and neck (torticollis), loss of upper body strength, abnormal neurological reflexes, and change in bowel/bladderfunctioning.

• hypothyroidism (10%). Prevalence increases with age• short stature – congenital heart disease, sleep related upper airway obstruction,coeliac disease, nutritional inadequacy due to feeding problems and thyroidhormone deficiency may contribute to this• over/underweight

Page 20: Down syndrome by Dr. Rubzzz

Which eyes belong to a child with Down syndrome?

• Epicanthal folds are prominent

• The iris has the light smudgy opacities of Brishfield spots

Page 21: Down syndrome by Dr. Rubzzz

Adolescence and Adulthood

• puberty - in Girls menarche is only slightly delayed. Fertility presumed- in Boys are usually infertile due to low testosterone levels

• increased risk of dementia /Alzheimer disease in adult life

• shorter life expectancy

Page 22: Down syndrome by Dr. Rubzzz

Gro

wth

Gro

wth

BW, length and HC are

BW, length and HC are

less in DS less in DS Reduced growth rate

Reduced growth rate Prevalence of obesity

Prevalence of obesity

is greater in DS

is greater in DSWeight is less than

Weight is less than expected for length in

expected for length in

infants with DS, and

infants with DS, and

then increases

then increases disproportion ally so

disproportion ally so

that they are obese by

that they are obese by

age 3-4 years

age 3-4 years

Page 23: Down syndrome by Dr. Rubzzz
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Page 25: Down syndrome by Dr. Rubzzz

DiagnosisDiagnosis

Prenatal screeningPrenatal screening-"triple screen" can be done between the -"triple screen" can be done between the

15th and the 20th weeks of pregnancy.15th and the 20th weeks of pregnancy.

1. Alpha-fetoprotein1. Alpha-fetoprotein

2.2. Unconjugated Estriol Unconjugated Estriol

3. Human Chorionic Gonadotropin (hCG)3. Human Chorionic Gonadotropin (hCG)

-PAPP-A-PAPP-A, which stands for pregnancy-associated plasma , which stands for pregnancy-associated plasma protein Aprotein A

Confirmed by Karyotype.Confirmed by Karyotype. 47,XX,21 47,XX,21 21q21q translocation, 21q21q translocation,

Page 26: Down syndrome by Dr. Rubzzz

Tests for positive results

If the prenatal screening is positive or are at a high risk for Down syndrome,

do further testing.

Amniocentesis• Done in midtrismester between 15 and 18 weeks of gestation. About 20 ml of amniotic fluid withdrawn for diagnostic studies. Usually taken in pregnant woman above 35 years old or older at the time of delivery.• risk of miscarriage is 1 in 300

Chorionic villus sampling (CVS)• Sample is taken by needle biopsy under ultrasound guidance. Advantage of this method is it can be taken earlier than Amniocentesis, usually between 10 and 12 weeks of gestation. • 1% risk of spontaneous miscarriage

Percutaneous umbilical blood sampling (PUBS)• To exam for chromosomal defects, blood is taken from the vein in the umbilical cord.•This test has a greater risk for miscarriage than both Amniocentesis and CVS.• Test usually is only done if completely necessary.

Page 27: Down syndrome by Dr. Rubzzz

ManagementManagement

1. Growth – Measurements should be plotted on the 1. Growth – Measurements should be plotted on the appropriate growth chart for children with DS.appropriate growth chart for children with DS.

This will help in prevention of obesity and early This will help in prevention of obesity and early diagnosis of celiac disease and hypothyroidism. diagnosis of celiac disease and hypothyroidism.

2. Cardiac disease – All newborns should be 2. Cardiac disease – All newborns should be evaluated by cardiac ECHO by 2 weeks (if clinical evaluated by cardiac ECHO by 2 weeks (if clinical examination or ECG were abnormal) or 6 weeks.examination or ECG were abnormal) or 6 weeks.

3. Hearing – Screening to be done in the newborn 3. Hearing – Screening to be done in the newborn period, every 6 months until 3 years of age and period, every 6 months until 3 years of age and then annually.then annually.

Page 28: Down syndrome by Dr. Rubzzz

Management (cont.)Management (cont.)4. Eye disorders - An eye exam should be 4. Eye disorders - An eye exam should be

performed in the newborn period or at least performed in the newborn period or at least before 6 months of age to detect before 6 months of age to detect strabismus, nystagmus, and cataracts.strabismus, nystagmus, and cataracts.

5. Thyroid Function – Should be done in 5. Thyroid Function – Should be done in newborn period and should be repeated at newborn period and should be repeated at six and 12 months , and then annually.six and 12 months , and then annually.

6. Celiac Disease – Screening should begin at 6. Celiac Disease – Screening should begin at 2 yrs. Repeat screening if signs/Sx develop.2 yrs. Repeat screening if signs/Sx develop.

Page 29: Down syndrome by Dr. Rubzzz

Management ( cont)Management ( cont)

7.7. Hematology – CBC with differential at birth to Hematology – CBC with differential at birth to evaluate for polycythemia as well as WBC.evaluate for polycythemia as well as WBC.

8.8. Atlanto-axial instability – X ray (14% in Atlanto-axial instability – X ray (14% in patient) for evidence of AAI or sub-luxation at patient) for evidence of AAI or sub-luxation at 3 to 5 years of age.; symptomatic in 1-2%.3 to 5 years of age.; symptomatic in 1-2%.

small risk for major neurological damage but small risk for major neurological damage but cervical spine X rays in children have no cervical spine X rays in children have no predictive validity for subsequent acute predictive validity for subsequent acute dislocation/ subluxation at the atlantoaxial dislocation/ subluxation at the atlantoaxial jointjoint

children with Down’s syndrome should not be children with Down’s syndrome should not be barred from taking part in sporting activitiesbarred from taking part in sporting activities

Page 30: Down syndrome by Dr. Rubzzz

Appropriate care of the neck while under general anasthesia or after road traffic accident is advisable

Page 31: Down syndrome by Dr. Rubzzz

TABLE 3Incidence of Some Associated Medical Complications in Persons with Down Syndrome

Disorder Incidence (%)Mental retardation > 95Growth retardation > 95Early Alzheimer's disease Affects 75% by age 60Congenital heart defects (atrioventricular canal defect, ventricular septal defect, atrial septal defect, patent ductus arteriosus, tetralogy of Fallot)

40

Hearing loss (related to otitis media with effusion or sensorineural)

40 to 75

Ophthalmic disorders (congenital cataracts, glaucoma, strabismus)

60

Epilepsy 5 to 10Gastrointestinal malformations (duodenal atresia, Hirschsprung disease)

5

Hypothyroidism 5Leukemia 1Atlantoaxial subluxation with spinal cord compression

< 1

Increased susceptibility to infection (pneumonia, otitis media, sinusitis, pharyngitis, periodontal disease)

Unknown

Infertility > 99% in men; anovulation in 30% of women

Page 32: Down syndrome by Dr. Rubzzz

MortalityMedian age of death has increased from 25 yrs in 1983 to 49 yrs in 1997, an average of 1.7 yrs increase per year.

Most likely cause of death is CHD, Dementia, Hypothyroidism and Leukemia.

Improved survival is because of increased placements of infants in homes andchanges in treatment for common causes of death.

Survival is better for males and blacks.

Page 33: Down syndrome by Dr. Rubzzz

Counse

ling

Counse

ling

May begin when a

May begin when a prenatal diagnosis is

prenatal diagnosis is

made.made. Discuss the wide range of

Discuss the wide range of

variability in manifestation

variability in manifestation

and prognosis.

and prognosis. Medical and educational

Medical and educational

treatments and

treatments and interventions should be

interventions should be

discussed.discussed. Initial referrals for early

Initial referrals for early

intervention, informative

intervention, informative

publications, parent

publications, parent

groups, and advocacy

groups, and advocacy

groups.groups.

Page 34: Down syndrome by Dr. Rubzzz

Famous people with Down syndrome

Chris BurkeJane CameronSujeet DesaiBernadette Resha

Page 35: Down syndrome by Dr. Rubzzz

Refe

rence

sRefe

rence

s

1. Pediatric Protocol for Malaysian

Hospital 2nd Edition2. Paediatric at a Glance 2nd

Edition3. Nelson Essential of Pediatrics

Fifth Edition.4. http://www.nichd.nih.gov/

health/topics/down_syndrome.cfm

Page 36: Down syndrome by Dr. Rubzzz

They need more loves and cares

Thank you