CYTOGENETIC CORRELATION OF CARDIAC AND NONCARDIAC ANOMALIES IN

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 Presentation at IIDSC -2017 New Delhi 10/09/2017

Introduction: § It is the most common genetic disorder in the world § Incidence: 1 in 1000 § Types as per chromosomal abnormalities: Sr Type of Down No 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%

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

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

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.

Results Table No: 1 Clinical Correlation with the different types of chromosomal abnormalities in Down’s syndrome (n=482 M: F- 1. 4: 1)Types of CA M Free Trisomy 21 F Total 249 173 422 Cardiac Non-Cardiac Anomalies 186/422 (44. 1%) 85/422 (20. 1%) CA in parents (n=36) Not available RT 21; 21 (n= 36) 21; 22 7. 470% 14; 21 12 -07 07 06 19 - 52. 77% 13 - 36. 11% 9/19 (47. 36%) 7/13 (53. 85%) 4/19 (21. 1%) 3/13 (23. 1%) 45, XY, t(21; 21)- 1 45, XX, t(14; 21)- 3 45, XY, t(14; 21)- 1 13; 21 15; 21 Mosaicism- 03 10 01 12 04 - 11. 11% 22 02/4 (50%) 03/10 (30%) 00 00 45, XY, t(15; 21)- 1 Not available 0 02 00 00 Not available 87. 55% 4. 56% No obvious CA 02 MMale, F- Female, 283 RT- Robertsonian CA-(42. 9%) Chromosomal Abnormality Total 199 482 Translocation, 207/482 92/482 (19. 1%)

Results Table No 2: Various Congenital cardiac Anomalies observed Cardiac Anomalies (207) No of cases % Atrioventricular Septal Defect 105 Ventricular Septal Defect Atrial Septal Defects Patent Ductus Arteriosus Tetralogy of Fallot Total 62 17 17 06 207 RT- Robertsonian Translocation Chromosomal abnormalities Free trisomy RT Mosaic 51 95/105 (90. 5%) 10 (9. 5%) - 30 8 8 3 100 60/62 (96. 7%) 13/17 (76. 5%) 5/6 (83. 3%) 186/207 (89. 85%) 2 (3. 3%) 2 (11. 7%) 3 (17. 6%) 1 (16. 7%) 18 2 (11. 7%) 1 (5. 9%) 3

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 t(14; 21) +21 (13) 3 3 1 7 t(15; 21) +21 (4) - 1 Mosaicism (22) - - 44 28 20 92 Total 18 (19. 56%)

Main findings of our study § Frequency of various chromosomal abnormalities observed§ Free trisomy 2187. 55% § Robertsonian Translocation- 7. 47% § Mosaicism 4. 56% § 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)

§ 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 2189. 85% § Robertsonian translocation- 8. 70% § Mosaicism 1. 45% § Non-cardiac anomalies observed- Duodenal atresia in 9%, imperforate anus in 6% and Hirschprung disease in 4% cases of DS

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

Thank you so much…… Dr. Dnyandeo Chopade Director and Consultant Medical Geneticist Genetic Health & Research Centre, Nashik Email- drchopade@Hotmail. com Mobile- + 91 9822885558