1. Down Syndrome
Dr.K.V.Giridhar
Associate Prof. of Pediatrics
GMC. Ananthapuramu, A.P.,
India.
4/28/2014 1

2. History
• Named after a physician, “John Langdon
Down” in 18th century.
• Described as Mongoloid child of
European parentage-”Mongolism”
• In 1959 a French doctor, named
“Jerome Lejeune”, discovered it was
caused by the inheritance of an extra
chromosome 21.
• Also known as “trisomy 21”
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3. Incidence
• Incidence classified according
to 3 major ethnic groups
•Malay - 1 in 981
•Chinese - 1 in 940
•Indians - 1 in 860
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4. Introduction
• Down syndrome is an autosomal
disorder because it affects
chromosome 21, which is an
autosome.
• Down syndrome is neither a dominant
nor recessive trait because it is just
an error in the “translation” process
of chromosome 21.
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5. Genetics of DS
• It is believed that the „amyloid precursor
protein gene (App)‟ is the cause of „Down
syndrome‟, and it is located on chromosome 21.
• A mutation in this gene usually results in
Alzheimer‟s disease . Similarly three copies of
this gene has a huge effect on the brain &
other tissues of body.
• Scientists believe that excess „App‟ gene is
causing the cells to die (apoptosis), because it
interfere with the normal cell division (mitosis).
• Therefore people with down syndrome tend to
develop the brain with signs of Alzheimer‟s and
abnormalities other parts of the body.4/28/2014 5

6. 92% -94% Trisomy 21
- nondisjunction during
fertilisation
2-4% Mosaicism
- error in cell division
after fertilisation
3-4% Translocation of
chromosome 21
- breaking and
attaching to other
chromosomes (14)
during cell division
4/28/2014 6

7. Down Syndrome & Maternal Age
A study done in Mysore,
India - paternal age and
maternal grandmother‟s
age influences Down
Syndrome in neonates.
Age Incidence of Down
Syndrome
< 30
30
35
36
37
38
39
40
42
44
46
48
49
Less than 1 in 1000
1 in 900
1 in 400
1 in 300
1 in 230
1 in 180
1 in 135
1 in 105
1 in 60
1 in 35
1 in 20
1 in 16
1 in 12
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8. 4/28/2014 8

9. Risk factors
• Advancing maternal age – usually
women of age 35 and above
• Mothers who already have one
child with Down syndrome –
increased risk for subsequent
pregnancies
• Parents who are carriers of the
genetic translocation for Down
syndrome4/28/2014 9

10. Clinical features
• Life expectancy : 55 years
(National Down Syndrome
Society)
• Physical appearances
– flat facial profile and an upward
slant to the eye
– short neck
– abnormally shaped ears
– white spots on the iris of the eye
(called Brushfield spots)
– single, deep transverse crease on
the palm of the hand.
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11. - relatively late development of
deciduous and permanent teeth as
compared with other children
- Teeth could appear in a different
sequence and positions
- Teeth are often are rounded, pointed
or cone-shaped. Smaller with gaps
- Fewer teeth.
- Maxilla is narrow, the tongue appears
too big for the mouth and the teeth
may be pushed out of place, as the
child grows older.
- Habit of breathing through the mouth
- Mental retardation varied from mild to
moderate – some even have special
abilities after training
and early interventions
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12. Neonatal features
• Flat facial profile
• Poor Moro reflex
• Excessive skin at
the nape of neck
• Slanted palpebral
fissures
• Hypotonia
• Hyper flexibility
of joints
• Dysplasia of pelvis
• Anomalous ears
• Dysplasia of
midphalanx of
fifth finger
• Transverse palmer
crease(simian)
4/28/2014 12

13. 4/28/2014 13

14. Percentage of dysmorphic features and physical
abnormalities in „Down syndrome‟ children
Dysmorphic features Current
study (%)
Kava
et al
(%)
Kumar
et al
(%)
Jones
(%)
Fryns
(%)
Upslanting palpebral fissures
Flat facial profile
Ears abnormality
Hypotonia
Simian crease
Sandle sign
Hypertelorism
Short stubby fingers
Protruding tongue
Clinodactyly
Epicanthic folds
Excessive skin fold on neck
89.3
64.9
56.1
52.6
36.8
33.3
33.3
24.5
19.2
19.2
17.5
12.2
83.9
50.9
66.9
76.3
33.2
46.2
33.9
-
29.9
36.1
56.9
36.8
-
-
-
80
40
-
-
-
-
50
60
-
80
90
60
80
45
-
-
-
-
50
-
80
80
90
50
21-77
48
45
-
-
-
62
40
81/85
4/28/2014 14

15. • Other Health-related problems
– Cardiovascular problems
• ventricular spetal defect, atrial septal defect, patent
ductus arteriosus
– Endocrine problems
• thyroid problems, diabetes mellitus
– Gastrointestinal problems
– duodenal, esophageal and anal
atresia,Hirschprung‟s disease
– Haematological problems
• Acute leukemia, transient myeproliferative disease
– Neurological problems
• Epilepsy, severe behavioral problems, Alzheimer‟s,
memory problems4/28/2014 15

16. – Sleep problems
• Sleep apnoea, other sleep disturbance
– Skeletal problems
• Flat foot, atlantoaxial subluxation
– Visual problems
• Refractive disorder, squint, nystagmus
– Hearing problems
• Hearing loss, conductive hearing loss, chronic otitis media
- Obesity and nutrient deficiency
- Malabsorption (probably linked with celiac disease) due to intestinal
damage
- Some has lack of vitamin B12, folic acid and zinc
- Need for antioxidants i.e. vitamin E
4/28/2014 16

17. Mental Retardation
• Almost all DS babies have MR.
• Mildly to moderately retarded .
• Starts in the first year of life.
• Average age of sitting(11 mon), and
walking (26 mon) is twice the typical age.
• First words at 18 months.
• IQ declines through the first 10 years of
age, reaching a plateau in adolescence that
continues into adulthood.
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18. Heart Disease
• 50 % of Down Syndrome pts have heart
disease
• Endocardiac cushion defects
• VSD
• Secundum ASD
• PDA
• Tetrology of Fallot
• Mitral valve prolapse
• AR, MR
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19. GI abnormalities
• 5% of cases
• Duodenal atresia or stenosis, sometimes
assoc with annular pancreas in 2.5 % of
cases
• Imperforate anus
• Esophageal atresia with TE fistula is less
common
• Hirschsprung‟s disease
• Strong assoc with celiac disease between
5 – 16 % ,4/28/2014 19

20. Growth
• Weight, length and HC are less in DS
• Reduced growth rate
• Prevalence of „obesity‟ is greater in
DS
• Weight is less than expected for
length in „infants‟ with DS, and then
increases disproportionally so that
they are obese by age 3-4 yrs
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21. Eye problems
Most common disorders are
 Refractory error – 35 to 76 %
Strabismus – 25 to 57 percent
Nystagmus – 18 to 22 percent
Cataract occur in 5 % of newborns,
Frequency increases with age.
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22. Brush field spots
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23. Hearing loss
• Unilateral or bilateral
• Conductive, sensorineural or
mixed
• Otitis media is a frequent
problem
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24. Hematologic disorders
• The risk of leukemia is 1 to 1.5 percent.
• 65% of newborn have polycythemia
resulting in hypoglycemia.
• Risk of AML and ALL is also much higher
than the general population.
• Transient leukemia – exclusively affects
NB.
- It is asymptomatic with spontaneous
resolution in 2-3 months.
4/28/2014 24

25. Endocrine disorder
• Thyroid disease –
Hypothyroidism occurs more
frequently than hyperthyroidism.
• Diabetes –
The risk of type 1 diabetes is
three times greater than that of
the general population.
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26. Reproduction
• Women with DS are fertile and may
become pregnant.
• Nearly all males with DS are
infertile. Due to impaired
„spermatogenesis‟.
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27. Skeletal abnormalities
• Excessive mobility of atlas (C1) and the
axis (C2), may lead to subluxation of
the cervical spine. (Atlantoaxial
instability )
• Diagnosis made by lateral neck
radiograph.
• flat foot, dysgenesis of middle phalax
in little finger, narrow maxilla,
clindactyly.
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28. Skin disorder
• Palmoplantar hyperkeratosis
• Seborreic dermatitis
• Fissured tongue
• Cutis marmorata
• Geographical tongue
• Xerosis
4/28/2014 28

29. Diagnosis
• Prenatal screening
• If no screening – It can be recognized
by the characteristic phenotypic
features.
• Confirmed by genetic Karyotyping.4/28/2014 29

30. Management
1. Growth – Measurements should be plotted
on the appropriate growth chart for children
with DS.
• This will help in prevention of obesity and
early diagnosis of celiac disease and
hypothyroidism.
2. Cardiac disease – All newborns should be
evaluated by cardiac ECHO for CHD in
consultation with pediatric cardiologist.
3. Hearing – Screening to be done in the
newborn period, every 6 months until 3 yrs
of age and then annually.4/28/2014 30

31. Management (cont.)
4. Eye disorders - An eye exam should be
performed in the newborn period or at least
before 6 months of age to detect
strabismus, nystagmus, and cataracts.
5. Thyroid Function – Should be done in
newborn period and should be repeated at
six and 12 months, and then annually.
6. Celiac Disease – Screening should begin
at 2 yrs. Repeat screening if signs develop.
4/28/2014 31

32. Management ( cont)
7. Hematology – CBC with DLC at birth to
evaluate for polycythemia as well as
leukemia.
8. Atlanto-axial instability – X ray for
evidence of AAI or sub-luxation at 3 to 5
years of age.
9. Alzheimer’s disease – Adult with a Down
Syndrome has earlier onset of symptoms.
When diagnosis is considered, thyroid
disease and possible depression should be
excluded.
10.Rehabilitation4/28/2014 32

33. Prevention
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34. Counseling
• May begin when a prenatal diagnosis is
made.
• Discuss the wide range of variability in
manifestation and prognosis.
• Medical and educational treatments and
interventions should be discussed.
• Initial referrals for early intervention,
and „rehabilitation‟.
4/28/2014 34

35. Mortality
Avarage life span is 25yrs. To 50 yrs.
Most likely cause of death is CHD,
AAI, Hypothyroidism and Leukemia.
Improved survival is because of
increased placements of infants in
„rehabilitation homes‟ and changes in
treatment for common causes of death.
Survival is better for males
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36. 4/28/2014 36