DOWN SYNDROME

BY
UMEONONUGBOR CHINENYE JANE

HOUSE OFFICER IN PEDIATRIC CARDIOLOGY UNIT, SEPT 2023

 Outline
• Case Summary
• Introduction
• Epidemiology
• Types of Down syndrome
• Aetiology
• Pathophysiology
• Clinical Preventation
• Investigations
• Treatment
• Differential diagnosis
• Prevention
• Reference
Case summary
• E . C is 4 months old female infant who presented at CHEW
with complaints of
• Poor weight gain x 4/12
• Worsening fast breathing x 4/12
• Easy fatiquibility x 2/12
• Fever x 1/52
She is a known patient of cardiology unit who was first diagnosed
at 2/12 of age
Mother is 39 yrs old I.T Analyst with tertiary level of education
Father is a 40 yrs old fashion designer with tertiary level of
education
Case summary
General Examination
Respiratory distress (flaring of alae nasai, intercostal
recession, subcostal recession), flat occiput, flat
nasal bridge, flat face, ocular telorism, epicanthal
folds, short finger, short neck, upward slanting
palpebral fissure, low set ears, sandal gap, not pale,
febrile (37.8 °c), not cyanosed SPO2 = 71% on room
air, moist buccal mucosa, no pedal edema.
• weight= 4.5 kg ↓
• Height= 62cm↓
Case summary
• CVS: Precordial bulge Pulse= 188 bpm apex beat=
6th left intercostal space midclavicular line. Heart
sounds = s1, s2 + grade 4/6 pan systolic murmur
maximum at left lower sternal border.
• Respiratory: RR=100cpm, reduced air entry
bilaterally, vesicular breath sounds.
• Abdomen: full moves with respiration soft,
heptomegaly= 6cm tender, spleen°, right and left
kidney°.
Case summary
• CNS: conscious and alert, OFC= 36.5 cm↓, head lag,
anterior fontanelle; flat and normotensive, hypotonia in
all limbs.
Investigation
ECHO done showed complex congenital heart disease;
double outlet left ventricle/ multiple artial septal defect/
ventricular septal defect/ patent ductus arteroisus/
pulmonary artery hypertension with moderate
pericardial effusion.
Managed for Trisomy 21 with complex congenital heart
disease , severe bronchopneumonia in heart failure.
Case summary
Child received iv cefuroxime, iv lasix , tabs
Aldactone, tabs sildenafil, Intranasal oxygen at
2l/min and vital signs monitored closely.
She improved clinically and was discharged after 1
week and placed on tabs aldactone , tabs lasix, tabs
sildenafil, susp zinnat

She is to follow up on outpatient CPC cardiology

clinic
Introduction
• Down Syndrome (DS) was named after John Langdon
Down (a British physician) in 1866.

• It’s the most common chromosomal disorder in humans

and commonest cause of intellectual disability

• Down syndrome also called Trisomy 21, is a genetic

condition in which a person is born with an extra
chromosome on the chromosome 21. The extra
chromosome causes delays in the way a child develops;
mentally and physically.
Introduction
• The physical features and medical problems
associated with Down syndrome can vary widely
from child to child.

• While some children with down syndrome need a

lot of medical attention, others lead healthy lives
Epidemiology
• The overall incidence is approximately 1 in 1000 live
births world wide.
• Incidence in UK is 1 in 750 live births
• Studies of down syndrome covering a period of 9
years revealed an incident of 1 in 865 livebirths in
University College Hospital, Ibadan, Southwestern,
Nigeria. ( Adeyokunnu A. 2019).
• In UPTH, of the 201 children seen in the Paediatrics
clinics over the last one year, 21 had features
suggestive of DS
• No sex or racial predilection
Epidemiology
Table 1: likely incidence of Down syndrome with increasing maternal age

Maternal age incidence

20 1 in 1,530

30 1 in 900

35 1 in 385

37 1 in 225

40 1 in 109

44 1 in 41
Epidemology
• Previous DS baby (1% risk of conceiving another
baby with DS)
• Women with DS (50% risk)
• Father with DS

• Carrier of chromosome 21 translocation (up to

100% risk)

• Paternal age > 42 yrs

Aetiology
• In 95% of Down syndrome, Chromosomes fail to
separate and both members move into one cell.

• A child gets an extra chromosome 21 during mostly

maternal oogenesis, 23+24= 47

• Its this extra genetic material that causes the

physical features and developmental delays
associated with Down Syndrome.
 Types of Down syndrome
There are 3 chromosomal patterns that result in Down
syndrome
1. Non disjunction (most common 90%)
2. Translocation (3% to 4%)
3. Mosaicism (1% to 2%)
Aetiology
• Trisomy 21 (Nondisjunction)
• Individuals with regular trisomy 21 have an extra
chromosome 21 in every cell. 47 chromosomes
instead of the usual 46.

• It occurs because of an usual cell division which has

produced either an egg or a sperm with 24.

• 23 + 24= 47 chromosome instead of 46 and all the

baby cells will have 47 chromosomes.
Aetiology
Robertsonian Translocation (3-4%)

• Longarm of chromosome 21 breaks off during cell

division and attaches to another chromosome (13, 14,
15, 21)

• Most cases are sporadic

• Maternal age is not linked to having baby with

translocation
Aetiology
Mosaicism ( 1%)

• Non-disjunction occurs after a few normal mitotic

divisions after fertilization.

• Some cells have 47 chromosomes and others, 46

chromosomes

• Less severe form

Pathophysiology

• Unclear

• The postulated hypotheses include

-Developmental instability (loss of chromosome
balance)
-The gene- dosage effect
Pathophysiology
Developmental instability (loss of chromosome
balance)
• The trisomic genes leads to a genetic imbalance

• Expression and regulation of many other genes

throughout the body
Pathophysiology
Gene–dosage effect: the gene located in chromosome 21 is
overexpressed in cells and tissues of Down syndrome
patients

• Down syndrome critical region 21q22. 1- q22.3 (DSCR),

contains the gene responsible for the congenital heart
diseases

• A new gene, DSCR1, in region 21q22.1-q22.2 is highly

expressed in the brain and the heart

• mutations in the hematopoietic transcription factor gene

(GATA 1) predisposes to leukaemias.
Pathophysiology
Clinical features
CHARACTERISTIC PHYSICAL FEATURES
FACE
Flat facial profile
Brachycephaly with flat occipiut
Wide open fontanelle

EYES
Upward slanting palpebral fissures
Prominent epicanthic folds
Brush field spots apparent in eyelid
White spot in the iris
Clinical features contd.
ENT
Hypoplastic nasal bones
Short nose with depressed nasal bridge
Small, low set ears with adherent earlobes
Short neck
Small oral cavity with protruding tongue
Small teeth with gaps
Hypotonia
Clinical features contd.
EXTREMITY
Transverse palmar crease
Sandal gap
Short fingers
Clinical Presentation
ORGAN MALFORMATION
HEART:
Usually present at birth with congenital heart
defect such as Atrioventricular septal defect
( endocardial cushion defect), ASD,VSD,PDA,TOF.
DIGESTIVE SYSTEM:
Presents with duoduenal atresia/stenosis, annular
pancreas, anal atresia, rectal prolapse,
Hirschsprung disease, megacolon.
Clinical Presentation
UROGENITAL:
Hypogonadism
Impaired spermatogenesis
Decrease fertility

ORTHOPEDIC:
Developmental hip dysplasia
Atlantoaxial dislocation
Clinical Presentation
ENDOCRINE:
Hypothyroidism
Type 1 diabetes
Decrease metabolism
Decrease physical activity
Increase obesity
Clinical manifestation
BEHAVIOURIAL /INTELLECTUAL/ DEVELOPMENT:
• Delayed motor development
• Muscle hypotonia
• Varying intellectual disability(average IQ is 50)
• Delayed developmental milestone(twice the normal age)
• Attention deficit hyperactive disorder
• Conduction disorder
• Early onset Alzhemiers
• Autism spectrum disorder
Clinical manifestation
Increase Risk of Malignancy:
•Acute lymphoblastic leukemia

•Acute myeloid leukemia.

•Immunocompromised and Infections; prone

to pneumonia and respiratory tract infections
Investigations
A clinical diagnosis requires ;
• Cytogenetic/Chromosomal studies, with Karotyping
of the infant.
In translocated down syndrome ,parent also need
karotyping.
• Fluorescence in situ hybridization test or
quantitative fluorescence PCR (QFPCR) may provide
rapid diagnosis.
Investigation
Prenatal screening
Screening is offered to women of all ages
• A nuchal translucnecy scan is done at 11-13 weeks of pregnacy.
• 2nd trimester (Quadruple Screen): 15-18 weeks Maternal
serum markers
-free β-human chorionic gonadotropin [β-hCG] (↑)
-unconjugated estriol – (↓)
-α-fetoprotein (↓)
-Inhibin-A (↑)
-detection rate is 80%. Combination of both detects 90%
PRENATAL SCREENING
Investigation
Diagnostic test should be done in suspected
screening population.
Prenatal test include;
• Chorionic villus sampling (CVS)
• Aminocentesis after 15 weeks of gestation.
Postnatal test include;
• Clinical features,
• QFPCR
• full Karotyping.
 DIAGNOSIS
Postnatal Diagnosis
• karyotyping
- done using blood cells, foetal skin cells, placenta,
bone marrow
- cell division is induced
- chromosomes arrested at metaphase and stained
with dyes
- each chromosome shows a specific pattern of light
and dark bands (G-banding) that differentiates one
from another
DIAGNOSIS
Other Investigations
• Detailed cardiovascular assessment along with
Echocardiogram
• Thyroid function test
• Immunoglobulin level
• Ophthalmological examination
• Hearing test
 MANAGEMENT
• Mainly symptomatic
• Multidisciplinary
• Regular follow up visits and screening
• Involves managing resulting medical conditions
• Supportive therapy (speech, physical,
behavioural, occupational)
• Assistive devices
• Counselling and support groups
SOCIAL ISSUES
• Stigmatization
• depression
• Victims of abuse
• Abandonment
• Care giver burn out
• Infertility
 PROGNOSIS
• Life expectancy has increased from 12yrs in
1912 to 50-60yrs present

• Recent advances in medical practice and

improvement in general care have contributed
to improved survival

• Associated medical conditions contribute to the

prognosis
 PREVENTION
LEVEL 1: General health promotion
• Genetic counselling

LEVEL 2: Specific Protection

LEVEL 3: Early Diagnosis and prompt treatment

• Routine newborn examination
• Prenatal screening
• Postnatal diagnostic tests
 PREVENTION
LEVEL 4: LIMITATION OF DISABILITY
• Routine screening
• Prompt treatment of associated medical
conditions
• Support and educational services
• Psychotherapy/ Support groups
• Optimize feeds
• Antibiotics
 PREVENTION
LEVEL 5: Rehabilitation
• Supportive therapy (e.g use of hearing aids)
• Educational services( special needs school)
• Occupational rehabilitation
• Psychotherapy, speech therapy
• Support groups
Differential diagnoses
• Congenital hypothyriodism

• Patau syndrome(trisomy 13)

• Edward syndrome(trisomy 18)

Reference
• Nelson Textbook of Pediatrics, vol 2, 20th edition,
2019.
• Illustrated Textbook of Pediatrics, 2nd edition,
2018.
• Adeyokunnu A.A, J Med Genet. 2022 Aug;19:277-
278 doi: 10.1136/jmg 19.4.277
• Netter Altas of Pediatrics, 1st edition
• Medscape
• Wikipedia
Thank You For Listening

World Down Syndrome

Day – March 21