1. DOWN SYNDROME
Emily Pollakowski, MD

2. Background
In 1866, Down described the clinical characteristics we know now as Down Syndrome
In 1959, Lejeune and Jacobs independently discovered trisomy 21 to be the cause
Most common and well known chromosomal abnormality
Most common cause of intellectual disability

3. Description
Down Syndrome is characterized by mental retardation, dysmorphic facial features, and distinctive phenotypic traits
Classically, hypotonia, flat facies, upslanting pqlpepral fissures, and small ears
Children with Down Syndrome have such a typical look that they look more like each other than their families

4. Associated Abnormalities: Cardiac
Congential heart disease (40-50%, most not symptomatic at birth)
AV canal (60%)
VSD
ASD
PDA
Tetralogy of Fallot
Aberrant subclavian artery

5. Associated Abnormalities
Hearing loss (66-75%)
Strabismus (33-45%)
Nystagmus (15-35%)
Refractive errors (50%)
Nasolacrimal duct stenosis
Delayed tooth eruption

6. Associated Abnormalities: GI
Tracheoesophageal fistula
GI atresia (12%)
Celiac disease
Meckel diverticulum
Hirschsprung disease (1%)
Imperforate anus

7. Associated Abnormalities
Renal malformations
Hypospadias
Cryptorchidism (5-50%)
Thyroid disease (15%): congenital hypothyroidism
Neonatal polycythemia
Leukemia (1%, 10-30x greater risk than general population)
Retinoblastoma and germ cell tumors

8. Associated Abnormalities
Obesity
Alopecia areata (10-15%)
Seizures (5-10%)
Alzheimer disease (nearly all over 40 years)
Mild to moderate mental retardation (IQ range )

9. Complications Otitis media with effusion (50-70%) Sinusitis
Tonsillar hypertrophy, leading to OSA (33-75%)
Obstructive bowel disease
Constipation

10. Complications Subluxation of hips Atlantoaxial instability
(10-20%, secondary to
ligamentous laxity)

11. Epidemiology Male > female (1.3:1)
75% of concepti with trisomy 21die in embryonic or fetal life
85% survive past one year of age
Over 50% are expected to live longer than 50 years
Congenital heart disease is most important factor in determining survival

12. Frequency In the United States, frequency is about 1 in 800 births
Each year, approximately
6000 children born with
Down Syndrome

13. Etiology Full Trisomy 21 (94%)
Most common error is maternal nondisjunction (failure to segregate) at the first meiotic division
Mosaicism ( 2.4%): 2 cell lines present, less severe
Translocation ( 3.3%): 50% de novo, 50% balanced translocation from one parent

14. Etiology
Advanced maternal age is risk factor for maternal meiotic nondusjunction
At 35 years, risk is 1 in 385
At 40 years, risk is 1 in 106
At 45 years, risk is 1 in 30

15. Diagnosis
Clinical diagnosis with classic constellation of dysmorphic features
History and physical!
Confirm with karyotype

16. Karyotype

17. History Previous history of infant with Down syndrome in the family
Parental concern about hearing, vision
Feeding history: adaquate calories, vomiting
Stooling pattern

18. History
Development: delay in cognitive abilities, motor or language development, social competence
Cardiac history:fainting episodes, palpitations
Symptoms of sleep apnea: snoring, daytime somnolence, behavioral changes, and school problems

19. History Symptoms of atlantoaxial instability: easy fatigability
neck pain, limited neck mobility or head tilt, torticollis
difficulty walking, change in gait pattern
loss of motor skills, incoordination
sensory deficits
spasticity, hyperreflexia

20. Physical General -Short stature -Hypotonia (80-100%),
with open mouth and
protruding tongue
-Midface hypoplasia

21. Physical Head -Brachycephaly with flattened occiput -Microcephaly Eyes
-Upslanting palpepral fissures (98%)
-Inner epicanthal folds
-Brushfield spots (speckled iris)

22. Physical
Ears
-Small, prominent, low set, overfolding of helix, small canals
Nose
-Small (85%), flat nasal bridge

23. Physical Tongue -Relative but not true macroglossia Mouth
-High arched palate
Teeth
-Missing (50%)
-Small, hypoplastic

24. Physical Heart -Assess for murmur, arrthymia Abdomen
-Look for distension in neonate (rule out obstruction)
-Diastasis recti GU
-In males, small penis and cryptorchidism

25. Physical Extremities -Broad hands, with short metacarpals
-Single transverse palmar crease (50%)
-5th finger with hypoplasia of midphalanx and clinodactyly (60%)
-Wide gap between 1st and 2nd toes
-Hyperflexibility of joints
Skin
-Fine, soft, sparse hair

26. Next steps Genetic counseling recommended
History of Down Syndrome increased risk of recurrence (1%)
Affected individuals rarely reproduce
Only 15-30% females are fertile
Males are infertile

27. Monitoring Routine vaccinations Medications Growth and development:
-Specific growth charts available
-Average age of meeting developmental milestones differs from general population

28. Monitoring
Cardiac
-Early evaluation and follow-up for congenital heart disease
-Endocarditis prophylaxis for certain lesions
Endocrine
-Thyroid function tests as newborn to rule out hypothryoidism, with follow-up

29. Monitoring Ophthalmologic -Early evaluation for cataracts and glaucoma
Ear, nose, throat
-Periodic audiologic exams
Orthopedic
-Screen for atlantoaxial instability with radiography

30. Monitoring Psychiatric/Social: -Screen for depression or anxiety
-Manage behavioral problems
-Social support
-Family support
-Long term living
arrangements

31. Prognosis Overall outlook dramatically improved
However, overall life expectancy reduced
Importance of empowering and supporting families as best we can