1. Dr. D. K. Chopade President, Down Syndrome Care Association, India
Presentation at IIDSC-2017
New Delhi
10/09/2017
Cytogenetic correlation of cardiac and non-cardiac anomalies in Down syndrome
Dr. D. K. Chopade President, Down Syndrome Care Association, India
Genetic Health & Research Centre, 7, Mahatmanagar, near ABB signal, Triambak Road, Nashik, Maharashtra

2. Introduction: It is the most common genetic disorder in the world
Incidence: 1 in 1000
Types as per chromosomal abnormalities:
Sr No
Type of Down Syndrome
Chromosomal abnormality
Prevalence 1
Free Trisomy 21
Three separate copies of chromosome 21
94% 2
Translocation Down syndrome
Extra copy of chromosome 21 is attached to other chromosomes like 21, 22, 13, 14 or 15
3.3% 3
Mosaic Down syndrome
Some cells show normal 46 chromosomes, while others show extra 21
2.4%

3. Karyotype of a boy with 21;21 Robertsonian translocaton Down syndrome
Karyotype of a boy with free trisomy 21 Down syndrome
Karyotype of a girl with 14;21 Robertsonian translocation Down syndrome

4. The major cause of early mortality is- Congenital heart defect
Clinical Features reported
Sr No
Principle features observed % 1
Hypotonia 80 2
Hyperflexible of joints 3
Excees skin on back of neck 4
Flat face 90 5
Slanted palpebral fissures 6
Abnormal auricles 60 7
Dysplasia of middle phalynx
Sr No
Major Congenital malformations observed % 1
CNS- Mental deficiency
100% 2
Cardiac- Atrioventricular defects
Ventricular septal defects
Patent Ductus arteriosus
Atrial septal defects
40% 3
Gastro-intestinal abnormalities
Tracheoesophageal fistula
Duodenal atresia
Pyloric stenosis
Hirschprung disease
Imperforate anus
12% 8
Dysplasia of pelvis 70 9
Simian crease 45
The major cause of early mortality is- Congenital heart defect

5. The aim of this study
To establish the clinical and cytogenetic correlation in the individuals with Down’s syndrome
Study Design
Retrospective analysis
482 individuals with Down syndrome,
Methods: clinical and cytogenetic evaluation
Period-2003 to 2015
Place of study-Genetic and Health Research Centre, Nashik, India.

6. Results
Table No: 1 Clinical Correlation with the different types of chromosomal abnormalities in Down’s syndrome (n= M:F- 1.4:1)-
Types of CA M F
Total
Cardiac Anomalies
Non-Cardiac Anomalies
CA in parents (n=36)
Free Trisomy 21
87.55%
249
173
422
186/422 (44.1%)
85/422 (20.1%)
Not available RT
(n= 36)
7.470%
21;21 12 07 %
9/19 (47.36%)
4/19 (21.1%)
45, XY, t(21;21)- 1
21;22 -- -
14;21 06 %
7/13 (53.85%)
3/13 (23.1%)
45, XX, t(14;21)- 3
45, XY, t(14;21)- 1
13;21
15;21 03 01 %
02/4 (50%) 00
45, XY, t(15;21)- 1
Mosaicism- 4.56% 10 22
03/10 (30%)
No obvious CA 02
283
199
482
207/482 (42.9%)
92/482 (19.1%)
M- Male, F- Female, RT- Robertsonian Translocation, CA- Chromosomal Abnormality

7. Results Table No 2: Various Congenital cardiac Anomalies observed
No of cases %
Chromosomal abnormalities
Free trisomy RT
Mosaic
Atrioventricular Septal Defect
105 51
95/105 (90.5%)
10 (9.5%) -
Ventricular Septal Defect 62 30
60/62 (96.7%)
2 (3.3%)
Atrial Septal Defects 17 8
13/17 (76.5%
2 (11.7%)
Patent Ductus Arteriosus
13/17 (76.5%)
3 (17.6%)
1 (5.9%)
Tetralogy of Fallot 06 3
5/6 (83.3%)
1 (16.7%)
Total
207
100
186/207 (89.85%) 18
RT- Robertsonian Translocation

8. Hirschprung’s disease
Results
Table No.3: Various Non-cardiac Anomalies Observed (Total Number- 92)
Chromosomal abnormality
Duodenal atresia
Imperforate anus
Hirschprung’s disease
Total
(92 cases)
Free trisomy 21 (422) 36 21 17
74 (80.43%)
t(21;21) +21 (19) 5 3 2 10
18 (19.56%)
t(14;21) +21 (13) 1 7
t(15;21) +21 (4) -
Mosaicism (22) 44 28 20 92

9. Main findings of our study
Frequency of various chromosomal abnormalities observed-
Free trisomy %
Robertsonian Translocation %
Mosaicism %
Male to Female ratio observed is 1.4:1
2 cases did not show any chromosomal abnormality
The most common Robertsonian translocation found was – t(21;21) followed by t(14;21)
Parents of children with Robertsonian translocation Down syndrome showed balanced Robertsonian translocation at a frequency of 16.7% (6/36)

10. CHD was observed in 42.95% of all cases with DS
The most common cardiac anomaly observed is Atrioventricular septal defect in 51% cases
Atrioventricular septal defect was observed with the highest frequency in translocation DS cases
Chromosomal abnormalities in children of DS with cardiac defects-
Free trisomy %
Robertsonian translocation- 8.70%
Mosaicism %
Non-cardiac anomalies observed- Duodenal atresia in 9%, imperforate anus in 6% and Hirschprung disease in 4% cases of DS

11. Conclusion
There is a close association between various types of chromosomal abnormalities and cardiac and non-cardiac malformations
The extra genetic material on chromosome 21 playes a vital role in development of major congenital malformations
All the children with Down syndrome should be investigated for the major cardiac and non-cardiac malformations

12. Thank you so much…… Dr. Dnyandeo Chopade
Director and Consultant Medical Geneticist
Genetic Health & Research Centre, Nashik -
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