The document provides a comprehensive overview of Down syndrome, detailing its definition as a genetic condition caused by trisomy 21, including its types, risk factors, clinical features, diagnostic evaluations, and management strategies. It highlights that early intervention can improve outcomes, while also emphasizing the variable prognosis and the importance of counseling for parents post-diagnosis. Additionally, it outlines screening and follow-up recommendations to monitor complications associated with the condition.

2. DOWN SYNDROME
By: Dr Saud Nisar
PGR (Paeds Unit – 11)

3. OBJECTIVES
To identify & understand the following about Down Syndrome
 Introduction
 Definition & its 3 types
 Etiology & Pathophysiology
 Risk Factors
 Clinical Features and Abnormalities
 Diagnostic Evaluation
 Management and Treatments
 Screening for Complications
 Prognosis
 Counselling

4. INTRODUCTION
• Down Syndrome is named after John
Langdon Haydon Down who first
described the physical and behavioral
characteristics in 1866.
• 1958 Jerome Lejeune and his team
identified trisomy 21 (47 chromosomes-
one extra chromosome 21 in cells) as
cause of Down Syndrome

5. DEFINITION
 Down Syndrome, also called Trisomy 21, is a
genetic condition that causes delays in physical
and intellectual development.
 There is extra genetic material from
chromosome 21, so individuals with Down
Syndrome have 47 chromosomes in total
instead of the usual 46.

6. Types On the basis of Pathophysiology
◦ Trisomy 21 or Non-Disjunction (95%): There is one extra copy of chromosome 21 (three
instead of the usual two) due to defect in meiosis, it is 97% maternal and 3% paternal.
◦ Translocation (3-4%): A segment of a 21 chromosome is found attached to other pairs of
chromosomes. It is also called ‘’Robertsonian translocations’’
◦ Mosaicism (1-2%): Nondisjunction occurs at a later stage of cell division, therefore, some
cells have the normal complement of 46 chromosomes and other cells 47 chromosomes
(with an extra 21 chromosome).

8. Figure showing Three copies at
chromosome 21

9. Who is at Higher Risk?
• Overall incidence of Down Syndrome is 1 out 733 live births.
• In Pakistan incidence of Down Syndrome is 1 in 300 live births.
• Every woman has small risk of chromosomal abnormalities. The risk increases as the
woman grows older.
.
Age of Mother Risk (approximate)
15-29 yr 1 in 1500
30-34 yr 1 in 800
35-39 yr 1 in 270
40-44 1 in 100
>45 yr 1 in 50

10. Carriers of Genetic translocation for Down Syndrome i.e if translocation in baby is
identified , carry out chromosomal analysis of both parents.
-if it is 21,21 translocation , there is 100% risk of Down Syndrome in next pregnancy.
-if any other Robertsonian translocation, risk is 5-7% if mother is translocation carrier
and 3-5% if father is translocation carrier.
Other risk factors…

11. Hall’s Criteria
 Head and Neck
• Flat face
• Upward slanting palpebral fissure
• Small dysplastic ears
• Short neck redundant skin
 CNS
• Poor Moro reflex
• Hypotonia
 Hands and Feet
• Single transverse palmer crease
• Short 5th
digit with clinodactyly
• Skeletal
• Hyperflexible joints
• Pelvic dysplasia

12. Clinical Features and Abnormalities
 CENTRAL NERVOUS SYSTEM
• Hypotonia
• Developmental delay
• Poor Moro reflex
 CRANIOFACIAL
• Brachycephaly with flat occiput
• Flat face
• Upward slanted palpebral fissures
• Epicanthal folds
• Speckled irises (Brushfield spots)
• Delayed fontanel closure
• Mild microcephaly
• Flat nasal bridge
• Protruding tongue,
• Open mouth Small dysplastic ears

13.  CARDIOVASCULAR
• Endocardial cushion defects
• Ventricular septal defect
• Atrial septal defect
• Patent ductus arteriosus
• Aberrant subclavian artery
• Pulmonary hypertension
MUSCULOSKELETAL
• Joint hyperflexibility
• Short neck, redundant skin
• Short metacarpals and phalanges
• Short fifth digit with clinodactyly
• Single transverse palmar creases
• Wide gap between first and second toes
• Pelvic dysplasia
• Short sternum
• Two sternal manubrium ossification centers
◦

14.  GASTROINTESTINAL
• Duodenal atresia
• Annular pancreas
• Tracheoesophageal fistula
• Hirschsprung disease
• Imperforate anus
• Neonatal cholestasis
 CUTANEOUS
• Cutis marmorata
 HEMATOLOGICAL
• Malignancies
• Immune dysfunction
 ENDOCRINE
• Hypothyroidism
• Diabetes mellitus

15. Conditions associated with Down syndrome

16. Diagnostic Evaluation
Prenatal Screening:
It is done in first in 1st
trimester by chorionic villus sampling and in 2nd
trimester by amniocentesis.
• First trimester (Triple screen, sensitivity 87%)
1) Fetal nuchal translucency
2) Beta-HCG
3) Pregnancy induced associated plasma protein A (PAPP-A)
• Second trimester (Quad screen, sensitivity 80%)
1) Beta- HCG
2) Inhibin
3) Unconjugated estriol
4) Alpha-fetoprotein
( Positive screening of 1st
and 2nd
trimester combined gives 95% Sensitivity)

17. Postnatal diagnosis:
Postnatal diagnosis of Down Syndrome is based on
• Physical Examination
• Chromosomal analysis (Karyotyping)
• Fluorescence in Situ Hybridization (FISH technique)
• Molecular Analysis (DNA testing to genetic material)

18. Management and Treatment
There is no cure for Down Syndrome ,but with multidisciplinary approach and early intervention It’s
complications can be prevented and treated by
Symptomatic treatment of infections and regular medical care
Speech therapy
Physical therapy
 Occupational therapy
Emotional and behavioral therapy
Genetic counseling

19. Screening for Complications
◦ Regular follow ups and screening helps in improving quality of life in Down Syndrome patients
Complications Screening schedule
Cardiac diseases (50%) At birth for Congenital Heart Disease
Young adult for acquired valvular disease
Eye examination (50%) At birth then annually
Hearing impairment (50-80%) At birth then 6 monthly till 3 years, then annually
Constipation At birth (For Hirschsprung disease)
Celiac disease (5-7%) At 2 years of age or whenever symptomatic
Hematologic disease At birth and adolescence or whenever symptomatic
Hypothyroidism (5-15%) At birth ,repeat at 6-12 months then annually
Growth and Development At each visit
Obstructive sleep apnea At 1 year and then in each visit
Atlanto-axial subluxation Each visit by history and examination, by X-rays at 3-5 year or symptomatic
or when plan to take part in contact sports
Psychiatric ,behavioral assessment At each visit

20. Prognosis
• Prognosis is variable depending on the types of complications of each baby.
• Without the heart defects, about 90% of Down Syndrome lives into their teens.
• Down Syndrome have an life expectancy of 50-55 years.
• Men with Down Syndrome appear to be uniformly sterile ( unable to have offspring).
• Women with Down Syndrome , however are fully capable of having babies, About 50% of these
babies however will also be born with Down Syndrome.
• As people with Down Syndrome age , they face an increased chance of developing the brain
disease called the (Alzheimer’s disease).

21. Counselling
• The parents should be informed 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.
• Inform about recurrence risks and possibilities of prenatal diagnosis.
• Tell the parents that their baby will affectionate, cheerful and good with humor.
• Her or his IQ will not be as good as normal child but with proper attention he or she will be
capable of self-help.
• He or she will be going to special schools made for these children.
• You will need to have regular follow ups and do testing as advised.
• Avoid further pregnancy as increasing age increases the risk of this condition in next pregnancy.