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History
First described by John Langdon Down, 1866
Trisomy 21 described by Professor Jérôme
Lejeune & Turpin in 1959
In 1975, NIH suggested that possessive use of
eponym should be discontinued in the USA, but
in England it remains Down’s Syndrome
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Aetiology There are three main types of chromosome
abnormalities in Down syndrome
1. Trisomy 21 (95 percent)
• an extra 21 chromosome. Instead of the normal number of 46
chromosomes in each cell, the individual with Down syndrome
has 47 chromosomes.
2. Translocation (3 - 4 percent)
• extra 21 chromosome is attached or translocated on to
another chromosome, usually on chromosome 14, 21 or 22.
3. Mosaicism (1 percent)
• some cells have 47 chromosomes and others have 46
chromosomes. Mosaicism is thought to be the result of an
error in cell division soon after conception.
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System wise problems in Down
Syndrome
CNS Intellectual disability
Alzheimer like disease after 25 yrs
Autistic behaviour
CVS CHD 40% - AV cushion defects before 10 mo.
Cor pulmonale
GIT Atresia of gut (Duodenal atresia – 8%)
Hirschprung’s disease
Otological Impaired hearing (60-70% - middle ear effusion)
Excessive Wax ( because auditory canal is narrow)
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Ocular Congenital cataracts 1% (correct before 3 mo.)
Nystagmus (5-30%)
Strabismus (23-44%)
Blepharitis (2-67%)
Refractive Errors (70-80%)
Tear duct stenosis
Cataract after 25 yrs (12-86%)
Immune
system
Frequent infections
Hepatitis B
Autoimmune diseases
Celiac disease
Trace element deficiency
System wise problems in Down
Syndrome
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Endocrine Congenital hypothyroidism 1%
Hypo or hyperthyroidism, Thyroid antibodies
Growth retardation
Orthopedic Muscle hypotonia
Joint laxity
Dislocation of patella and hip
Hallus valgus
Atlantoaxial dislocation (10% radiologically)
Urogenital Renal hypoplasia , post urethral valves
Cryptorchidism, hypospadiasis
Boys - Sterility
System wise problems in Down
Syndrome
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Diagnosis
Prenatal
U/s – Double bubble
Echo - AV canal defects
X- Ray – Short femur or humerus
Echogenic small bowel - Double bubble
appearance
Postnatal
Physical examination
Confirmation
Chromosome evaluation
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During 1st and 2nd trimester serum
testing
What is measure When is it
measured
Where does it
come from
Other information
Pregnancy associated
plasma protein-A
(PAPP-A)
1st
trimester
Produced by the
baby and placenta
Very low in mother’s blood can indicate
poor placentation
Beta human chorionic
gonadotrophin (bhCG)
1st and 2nd
trimester
Produced by the
baby
High levels of bhCG in mother’s blood
indicate problems with pregnancy like fetal
growth restriction
Unconjugated oestriol
(uE3)
2nd
trimester
Produced by the
placenta
Very low levels of uE3 indicate biochemical
disorder of Smith Lemli Opitz syndrome,
steroid sulphatase deficiency
Alfa fetoprotein (AFP) 2nd
trimester
Produced by the
baby
Very high AFP in absence of structural
anomalies indicate problem of pregnancy
(fetal growth restriction)
Inhibin A 2nd
trimester
Produced by the
placenta
Very high levels indicte poor placentation
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Preventive Screening – 1st
Trimester
Maternal serum PAPP – A * Increased
Maternal free b hCG Increased
Fetal nuchal translucency
thickness
> 4 mm (USG)
*pregnancy-associated plasma protein A
* Blood collected ideally between 9 -1 2W
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Preventive Screening
1
• Serum a-fetoprotein
• Decreased
2
• Unconjugated estradiol level
• Decreased
3
• Human chorionic gonadotrophin
• Incresed
Triple Test
(Kettering test or the Bart's test)
– Done during 2nd trimester
– 65% detection rate
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Preventive Screening 2nd
trimester
1
• Serum a-fetoprotein
• Decreased
2
• Unconjugated estradiol level
• Decreased
3
• Human chorionic gonadotrophin
• Incresed
4
Inhibin A
• Increased
Quadruple Test - 75% detection rate
* Blood collected ideally between 15 -17 W
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3 D CT image of pelvis : Broad, laterally flattened iliac wings
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For couples who come late or opt for the initial
screening with serum markers and
ultrasonography
Karyotyping by amniocentesis (16— 18 weeks) or
transabdominal CVS, or cordocentesis (after 18
weeks).
The karyotype results are available within a week with
cord blood samples and direct CVS preparations.
The results of amniotic fluid cultures take about 2- 3
weeks.
The risk of fetal loss after CVS is about 3—4% and
with cordocentesis it is about 3%.
Amniocentesis poses the lowest risk of about 0.5-1%.
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Non-invasive Prenatal Screening
Analyzing cell-free fetal DNA in maternal serum is an
important advance in prenatal diagnosis of Down
syndrome.
Next-generation DNA sequencing has reduced the cost
of this procedure, which has a high degree of accuracy
(98% detection rate) and applicability.
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Down syndrome Screening - overview
SCREENING TEST DETECTION
RATE (%)
1st
Trimester
NT measurement 64-70
NT measure + PAPP-A, free or total b-hCG 82-87
2nd
Trimester
Triple screen (metarnal serim AFP, hCG, uE3) 69
Quadruple screen (metarnal serim AFP, hCG, uE3
+ Inhibin A)
81
1st and 2nd
Trimesters
Integrated (NT, PAPP-A, quadruple screen) 94-96
Serum integrated(PAPP-A, quadruple screen) 85-88
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Treatment : Goals
Appropriate and timely management of age-
specific Down syndrome–related medical and
developmental conditions
Early intervention for maximal potential of
developmental skills including occupational,
speech, and physical therapy
Injury and abuse prevention
Identify and refer family or caregivers to
financial and medical support programs
Develop an individual education plan before
transition to preschool
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Management
Early stimulation : involve therapists and special educators
whose goal is to help the baby develop motor skills,
language, social skills and self-help skills
Physiotheroapy
Antioxidants like Zn – Alzheimer’s disease
AEDs – for epilepsy
CVS / GI Abnormalities : Corrective surgeries
Refractory errors : Appropriate lenses
Speech & Language Defects: Specialist speech therapies
Anemia: Appropriate nutrients
Hypothyroidism : Thyroxine
Skin disorders : Moisteners, appropriate therapies
Low cholesterol diet
Immune deficiencies: Vitamin C and Antibiotics
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Management - Monitoring
Hearing tests - at birth or by 3 months of age.
A complete blood count (CBC).
Check for signs of leukemia.
Thyroid evaluation
Heart evaluation
X-rays to evaluate bones in the neck
Dislocation of the neck bones (atlantoaxial dislocation).
between ages 3 and 5 to look for signs of loose ligaments that
may lead to dislocation.
Evaluation for Sleep Apnea
Eye testing – once in an year
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Life Expectations
The typical life expectancy of people with
Down syndrome has nearly doubled in
recent decades, from 25 years in 1983 to
49 years in 1997
About 13% of people with Down syndrome
live longer than 68 years
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Down Syndrome is inherited as ..
A. Autosomal recessive
B. X-linked recessive
C. Autosomal dominant
D. All of the above
E. None of the above