Down Syndrome

All the important aspects of Down Syndrome are covered in this presentation. Helpful for all medical students.

1. D OWN SYNDROME Dr.Jishnu.K.R

2. Introduction It is named after Langdon Down who first described it in 1866. Most common chromosomal disorder (frequency of 1 in 733 ). Occurs more often when the mother conceive at older age. Risk Age of the mother 1:1550 15-29 yr 1:800 30-34 yr 1:270 35-39 yr 1:100 40-44 yr 1:50 > 45 yr

3. CYTOGENETICS

4. Cytogenetics 1. Meiotic non-disjunction of chromosome 21 (9 5 %) May produce an extra copy of chromosome 21 (Trisomy 21) in egg (95%) or sperm (5%). May be of maternal (97%) or paternal (3%) origin. In most cases, the origin is maternal where the mother conceive at older age.

5. Due to older age, the maternal oocyte is exposed to harmful environmental influences for a longer period. Other predisposing factors are radiation, viral infections and genetic predisposition. The sperm has a short lifespan and therefore has less chances of injurious exposure.

6. 2 . Translocation ( 4 %) - Majority of translocations in downs syndrome are fusions at the centromere between chromosomes 13,14,15 ,21 and 22 known as robertsonian translocation.

7. 3. Mosaicism (1%)

8. CLINICAL FEATURES OF DOWNS SYNDROME IN THE NEONATAL PERIOD 1) CNS - Hypotonia - Devolopmental Delay -Poor Moro Reflex 2) CRANIOFACIAL -Brachycephaly with flat occiput -Flat face -Upward slanted palpebral fissures -Epicanthal folds

9. - Speckled Irises(Brushfield spots) -Three fontanels -Delayed fontanel closure -Frontal sinus and midfacial hypoplasia -Mild microcephaly -Short , hard palate -Small nose,flat nasal bridge

10. -Protruding tongue,open mouth -small dysplastic ears 3) CARDIOVASCULAR -Endocardial cushion defects -VSD -ASD -PDA -Aberrent subclavian artery -Pulmonary Hypertension

11. 4)MUSCULOSKELETAL -Joint hyperflexibility -Short neck,reduntant skin -Short metacarpals and phalanges -Short 5th digit with clinodactyly -Single transverse palmar crease -Wide gap between 1st and 2nd toes -Pelvic Dysplasia -Short sternum

12. 5) GASTROINTESTINAL -Duodenal atresia -Annular pancreas -Tracheoesophageal fistula -Hirschsprung disease -Imperforate anus -Neonatal cholestasis 6)CUTANEOUS -Cutis marmorata -Most males with Down Syndrome are sterile, but some females have been able to reproduce with a 50% chance of having trisomy 21 pregnancies -Life Expectancy of Children with Down syndrome is approximately 50-55years

13. HALLS CRITERIA 1)Hypotonia 2)Poor Moro reflex 3)Flat face 4)Upward slanted palpebral fissures 5)Small dysplastic ears 6)Joint hyperflexibility 7)Short neck, redundant skin 8)Short 5th digit with clinodactyly 9)Single transverse palmar creases 10)Pelvic dysplasia

14. Associated Abnormalities 1. Congenital heart disease (CHD) - 40% Endocardial cusion defects (40-60%) Most significant factors in determining survival. 2 . Gast r ointest i nal malformations Atresias in 12% of cases (esp duodenal atresia) Increase d risk of annular pancreas and Hirschprung disease. 3. Eye problems - Increase risk of cataract, nystagmus, squint, and abnormalities of visual acuity . 4. Hearing defects - Prone to serious otitis media.

15. Associated Abnormalies 5. Thyroid dysfunction 13-54% have hypothyroidism. Thyroid function test recommended during neonatal period. 6. Atlanto-occipital subluxation - Displacement of atlanto-occipital joint can cause cord compression. - 10-30% cases

16. Associated Abnormalies 7. Physical growth. Linear growth is retarded and tend to become obese with age. Muscle tone improves with age whereas the developmental progress slows with age. Regular followup for height and weight is necessary. 8. Malignancies - Prone to develop lymphoproliferative disorders, including acute lymphoblastic leukemia (ALL) , acute myeloid leukemia (AML) , myelodisplasia and transient lymphoproliferative syndrome.

17. Prenatal Diagnosis I ndication for screening and diagnostic tests : All women should be offered screening of Down syndrome Even though younger women have a lower risk , they represent half of all mothers with babies with Down Syndrome because of their higher overall birth rate.

18. Screening Tests 1. 1 st trimester (11-12weeks) - Ultrasound : Measurement of nuchal translucency (NT) - Exc e ss nuchal fluid accu m u l ation is produced i n down’s syndrome foetus Absent nasal bone - Maternal Serum Tests : Serum Beta-HCG(increased) Pregnancy-associated plasma protein(PAPP-A)(Decreased)

19. Nuchal Translucency alone can detect <70% cases. Nuchal Translucency + Maternal serum testing of first trimester(Beta-HCG and PAPP-A) can detect 87% cases

20. 2. 2 nd trimester (16-20weeks) - Ultrasound increased nuchal fold thickness Short femur and humerus - Maternal Serum Tests : (a) Triple tests: Alpha-Fetoprotein(decreased) U nconjugated oestriol (decreased) Beta- HCG (increased) -Triple tests can detect 70% cases

21. (b) Quadruple tests: Alpha-Fetoprotein(decreased) U nconjugated oestriol (decreased) Beta- HCG (increased) Inhibin-A(increased) - Quadruple Test can detect 80% of cases. - Both Triple and Quadruple Tests have 5% false positive rates

22. INVASIVE PRENATAL TESTING 1. Chorionic villus biopsy(10-12 weeks) 2.Amniocentesis (16-20 weeks) 3.Cord blood sampling(after 18 weeks) - Detection of cell-free fetal DNA in maternal plasma is replacing conventional 1st and 2nd trimester screens. -It has 98% detection rate.

23. Management and Prognosis Principle : early stimulation, physiotherapy and speech therapy. Associated problems need to be treated as required. Social performance is usually achieved beyond that expected for mental age. They behave as happy children, friendly, good sense of rhythm and enjoy music.

24. Major cause of early mortality is CHD (almost 50% die in infancy) Other common diseases : Chronic rhinitis Conjunctivitis Periodontal disease Lower respiratory tract infections and hematological malignancies (ALL and AML) are another cause of increased mortality.

25. Counseling T he parents should be : Informed about the disorder as early as possible after diagnosis is confirmed. Talk in simple and positive language giving hope, and allow sufficient time to the parents to ask questions. Discuss known problems and associated disorders. Not talk about institutionalisation and adoption, unless asked. Both these options should be discouraged. Inform about recurrence risks and possibilities of prenatal diagnosis.

26. Risk of Recurrence Women with age 35 years or less who have a child with trisomy have a 1% risk of having another. Risk is little increased if the mother is at risk and 35 years or older. For translocations inherited from the mother, the risk is about 10% and 4-5% if inherited from father.

27. Translocation (21;21) have 100 % recurrence risk. Translocation (14;21) have a 5-7 % of recurrence risk.

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