DOWN SYNDROME

WHAT IS DOWN SYNDROME

Down syndrome (DS) is the most common chromosome abnormality
among liveborn infants.

It is the most frequent form of intellectual disability caused by a

microscopically demonstrable chromosomal aberration
DS is characterized by a variety of dysmorphic features, congenital
malformations, and other health problems and medical conditions.

Not all of them are present in each affected person

 INCIDENCE
Worldwide, the incidence of Down syndrome is estimated to be about
one in every 1000 births.

In the United States, it is estimated that about 6000 babies are born each
year with Down syndrome, which means around one in every 700 babies
has the condition.
Women who are 35 years or older are at the greatest risk for giving birth to an infant
with DS

• 35 years: 1/400 live births

• > 40 years: 1/110 live births

According to the CDC, younger mothers (< 35 years) who smoke and use oral
contraceptives are at an increased risk as well.

Despite many years of research, advanced maternal age has been the only one factor
that is well established with DS.
Age Risk
25 1 in 1,250

30 1 in 900

35 1 in 350

40 1 in 100

45 1 in 30

49 1 in 10
ETIOLOGY & PATHOPHYSIOLOGY
Humans usually have 46 chromosomes in every cell, with 23

inherited from each parent. Due to the extra copy of chromosome 21,

people with Down syndrome have 47 chromosomes in their cells. This

additional DNA causes the physical characteristics and developmental

problems associated with the syndrome.

TYPES
• Non-DisjunctionTrisomy 21 (95%): The extra 21
chromosome (three instead of the usual two) produces a
complement of 47 chromosomes.

• Translocation (3-4%): A segment of a 21 chromosome is

found attached to other pairs of chromosomes.

• Mosaicism (1-2%)
CLINICAL FEATURES
• Hypotonia
• Poor Moro reflex
• Upslanting palpebral fissures
• Epicanthic folds
• Flat facial profile/flat nasal bridge
• Low-set small ears
• Brachycephaly
• Open mouth
• Protruding tongue
• Short neck
• Excessive skin at nape of the neck
CARDIOVASCULAR DISEASE
Approximately one-half of individuals with DS have congenital heart
disease

• Complete atrioventricular septal defect (CAVSD) – 37 percent

• Ventricular septal defect (VSD) – 31 percent

• ASD – 15 percent

• Partial atrioventricular septal defect (PAVSD) – 6 percent

• Tetralogy of Fallot (TOF) – 5 percent

• PDA – 4 percent
GASTROINTESTINAL ABNORMALITIES
Children with trisomy 21 are at increased risk for gastrointestinal tract
anomalies, which occur in approximately 5 percent of cases

Duodenal atresia or stenosis is the most characteristic lesion,

occurring in 2.5 percent

Others:
Hirschsprung disease
Imperforate anus
Esophageal atresia with tracheoesophageal fistula
A strong association appears to exist between DS and celiac disease.
EYE PROBLEMS
Refractive errors
Nystagmus
Cataracts 
Glaucoma
HEARING PROBLEMS
Hearing impairment affects 38 to 78 percent of individuals with DS

Otitis media is a frequent problem, affecting 50 to 70 percent of DS

children, and it is often the cause of hearing loss in this population
NEUROPSYCHIATRIC DISORDERS
Cognitive impairment

Developmental impairment becomes apparent in the first year of life. In

general, the average age of sitting (11 months), creeping (17 months),
and walking (26 months) is approximately twice the typical age. And
the first word at 18 months

Attention-deficit hyperactivity disorder

Autism

Dementia/Alzheimer disease (in adullts)

ENDOCRINE DISORDERS

Hypothyroidism (Most Common)

Hyperthyroidism

Diabetes 
REPRODUCTION
Females with DS are fertile and may become pregnant.

Nearly all males with DS are infertile.

The mechanism is impairment of spermatogenesis

DIAGNOSIS
PRENATAL TESTING
Combined screening test
Maternal serum levels of beta hCG and Pregnancy Associated Plasma
Protein - A (PAPP-A) + Nuchal Transluscency (NT) scan done

Quadruple test :Maternal serum beta hCG, alphafetoprotein (AFP),

inhibin A, and unconjugated oestriol (uE3).
SENSITIVITY
1st Trimester Screening Test 85% as whole
Nuchal Thickness 60-75%
Maternal Serum Marker (PAPP-A & Beta HCG) 65%

2nd Trimester Screening Test

Triple test (AFP, hCG, Estriol) 70%
Quadruple (AFP, hCG, Estriol and Inhibin-A) 76%

1st & 2nd Trimester 94%

MANAGEMENT
Growth – Measurements should be plotted on the appropriate growth chart for
children with DS.

Cardiac disease – All newborns should be evaluated by cardiac ECHO for CHD in
consultation with pediatric cardiologist.

Hearing – Screening to be done in the newborn period, every 6 months until 3 yrs
of age and then annually.

Eye disorders - An eye exam should be performed in the newborn period or at least
before 6 months of age to detect strabismus, nystagmus, and cataracts.
Thyroid Function – Should be done in newborn period and should be repeated at six and 12
months, and then annually.

Celiac Disease – Screening should begin at 2 yrs. Repeat screening if signs develop.

Hematology – CBC with DLC at birth to evaluate for polycythemia as well as leukemia.

Atlanto-axial instability – X ray for evidence of AAI or sub-luxation at 3 to 5 years of age.

Rehabilitation
MORTALITY
Average life span is 25yrs to 50 yrs.

Most likely cause of death is CHD, Hypothyroidism and Leukemia.

Improved survival is because of increased placements of infants in rehabilitation

homes and changes in treatment for common causes of death.