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TRISOMY 21-
TRISOMY 21-
DOWN DOWN
SYNDROMESYNDROME
Dr. RubzzzDr. 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.
IncidenceIncidence
Approximately one in 800-
Approximately one in 800-
1000 live births.
1000 live births.
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
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
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%
24,X +21
23,Y
47,XY,+21
Egg,extra 21
Sperm, normal
Zygote
Trisomy 21 in Down Syndrome
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)
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
Medical Problem
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
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%
• 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
Which eyes belong to a child with Down syndrome?
• Epicanthal folds are prominent
• The iris has the light smudgy opacities of Brishfield spots
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
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
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,
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.
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.
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.
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
Appropriate care of the neck while under general anasthesia or after road traffic accident is advisable
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
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.
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.
Famous people with Down syndrome
Chris BurkeJane CameronSujeet DesaiBernadette Resha
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
They need more loves and cares
Thank you