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 Trisomy 21 is the most
common autosomal chromosome aberration occurring in
approximately 1:700 live births.
• The risk of a Trisomy 21 pregnancy rises with increasing maternal
age. Clinically Trisomy 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, Epicanthal folds, Hypertelorism
• Brushfield spots
• Refractive errors (e.g., Short-
sightedness, Astigmatism, Strabismus)
• 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
• Brachydactyly
• Soft tissue: ↑ increased risk of umbilical and inguinal hernias;
marked hyperextension of joints may occur
• Atlantoaxial instability: Loss 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
• Atrioventricular Septal Defect
• Ventricular Septal Defect
• Tetralogy Of Fallot
Gastrointestinal tract
• Duodenal atresia
• Imperforate Anus
• Enlargement of the colon
• Rectal prolapse
• Hirschsprung disease

9. Urogenital system
• Hypogonadism
• Cryptorchidism
• Decreased fertility in men
Further features
• Hypothyroidism
• Celiac Disease
• Sleep Apnea
• Hearing loss due to recurrent Otitis Media

10. • ↑ risk of Leukemia
• ↑ risk of early onset of Alzheimer disease
• ↑ risk of developing Epilepsy
Height and development
Motor skills
• Delayed motor development
• Muscle hypotonia
Height: Reduced growth with shortening of long bones

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

12. SIMIAN CREASE

14. FLAT NASAL BRIDGE

15. MICROCEPHALY

16. SANDAL GAP

17. CLINODACTYLY

19. DIAGNOSTIC EVALUATION
Prenatal screening
Counselling precedes screening procedures; provide information that
screening is voluntary; explain options of terminating
the pregnancy if Trisomy 21 is diagnosed.
Screening procedures
a) 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

20. b) Second Trimester Quadruple Test (15–18 weeks)
• Screens for Trisomy 18 and 21. (Trisomy 21: ↓ Free
Estriol, ↓ Alpha-Fetoprotein (AFP), ↑ Inhibin A and ↑ human
chorionic gonadotropin (β-hCG)
c) Cell-free fetal DNA (cfDNA)
d) Diagnostic Fetal Karyotyping: Test used to identify and evaluate the
size, shape, and number of chromosomes in a sample of cells.
e) Amniocentesis
f) CVS (Chorionic Villi Sampling)

21. 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.