Down Syndrome

Genetics Lecture for B.Sc Nursing II Year

1. Down’s syndrome Mrs Bincy Varghese Associate Professor Nursing

2. introduction Down syndrome, also known as  T risomy  21 is the most common autosomal chromosome aberration occurring in approximately 1:700 live births. The risk of a  T risomy  21  pregnancy   rises with increasing maternal age. Clinically T risomy  21 manifests as a syndrome involving a characteristic appearance, organ  malformations and mental disability . Down syndrome is by far the most common and best known chromosomal disorder in humans and the most common cause of Intellectual Disability. It is primarily caused by trisomy of chromosome 21. However not all defects occur in each patient; there is a wide range of phenotypic variation.

3. epidemiology Most common autosomal chromosome aberration (1:700 live births). The risk of a Down syndrome  pregnancy  rises with maternal age Maternal Age Incidence 20 1:1500 30 1:900 40 1:100 45 1:30 50 1:6

4. etiology Non-disjunction  occurs in approx. 70% of cases in  meiosis   In about 95% of cases, there is an extra whole chromosome 21 (trisomy 21), which is typically maternally derived. Translocation occurs when genetic material from chromosome 21 becomes attached to another chromosome resulting in 46 chromosomes with 1 chromosome having extra material from chromosome 21 attached.

5. Clinical features Facial and  cranial  features (Craniofacial Dysmorphia) Eyes Upward slanting of the eyelids,  E picanthal folds ,  Hypertelorism Brushfield spots   Refractive errors  (e.g.,  S hort-sightedness ,  A stigmatism ,   S trabismus ) Cataracts  (congenital, infantile, or juvenile)

6. Mouth Small oral cavity, large tongue High arched palate Abnormal teeth   Further features Brachycephaly  Hypoplastic nasal bones, broad and flat nasal bridge Ear anomalies (small, round low-set ears)

7. Extremities, soft tissue and skeletal features Single  transverse palmar crease Sandal gap Clinodactyly B rachydactyly Soft tissue: ↑ increased risk of umbilical and  inguinal hernias ; marked hyperextension of  joints  may occur Atlantoaxial instability : L oss of ligamentous stability between the atlas (C1) and axis (C2) which can result in compression of the spinal cord

8. Organ  malformations  and associated conditions Heart A trioventricular Septal Defect V entricular Septal Defect T etralogy Of Fallot Gastrointestinal tract D uodenal atresia I mperforate Anus E nlargement of the  colon R ectal prolapse Hirschsprung disease

9. Urogenital system H ypogonadism C ryptorchidism D ecreased  fertility in men Further features H ypothyroidism C eliac D isease S leep   A pnea H earing l oss  due to recurrent  O titis M edia

10. ↑ risk of  L eukemia ↑ risk of early onset of Alzheimer disease ↑ risk of developing  E pileps y Height and development Motor skills Delayed motor development Muscle hypotonia Height :  R educed growth with shortening of long bones 

11. Obesity :  P revalence  approx. 50% higher than in general population  Intelligence Varying levels of  intellectual disability  (average IQ: 50) Apparent within first 12 months:  D evelopmental milestones  (e.g., sitting, walking, talking) achieved at approx. twice the age of healthy children

12. SIMIAN CREASE

13. FLAT NASAL BRIDGE

14. microcephaly

15. SANDAL GAP

16. clinodactyly

17. Diagnostic evaluation Prenatal screening Counselling precedes screening procedures; provide information that screening is voluntary; explain options of terminating the  pregnancy  if  T risomy  21 is diagnosed. Screening procedures   First Trimester Combined Test  (11–13 weeks) Ultrasound Nuchal Translucency  Measurement (thickened nuchal fold), Absent or  hypoplastic   nasal bone , Shortened middle  phalanges  of the fifth digits with clinodactyly, Shortened  long bones Maternal serum: ↓  ( PAPP-A ); ↑  β- hCG

18. Second Trimester  Quadruple T est  (15–18 weeks) Screens for  T risomy 1 8  and 21 . ( Trisomy  21: ↓  Free Estriol , ↓  Alpha-Fetoprotein  ( AFP ), ↑  I nhibin A  and ↑  human chorionic gonadotropin  ( β- hCG ) Cell-free  fetal   DNA  ( cfDNA ) Diagnostic F etal   K aryotyping : T est used to identify and evaluate the size, shape, and number of chromosomes in a sample of cells. Amniocentesis CVS (Chorionic Villi Sampling)

19. Postnatal Diagnostics Screening for associated conditions. Treatment Symptomatic Management of the associated conditions Educational awareness, Social support Prognosis Average life expectancy approx. 50 years Mortality mostly due to organ malformation and immunodeficiency.