What’s up with Down Syndrome?

Sheryl Kho M.D.

PGY-3

Origins

16th century 1866, Dr. John Langdon Down Superintendent Earlswook Asylum for

children with MR Surrey, England Cretins vs. “mongoloids”

Dr. John L. Down

Origins

1930: Waardenberg & Bleyer- speculated DS could be due to a chromosome abnormality

1959: Jerome Lejeune & Patricia Jacobs- determined cause to be trisomy 21

Genetics Chromosomal disorder, triplication of

chromosome 21

Genetics

Genetics

Genetics

21st Chromosome & Down Syndrome

Overexpression of genes increased production of certain products

Genes that may have input into DS:SOD1-superoxide dismutase 1; premature

aging, decreased immune systemCOL6A1-heart defectsETS2-skeletal abN, leukemiaDYRK- mental retardationCRYA1- cataracts

Epidemiology

1 in 800 births6000 born per year75% die in conception, 85% survive up

to 1 year, 50% survive up to age 50 years

No race1.15 males to 1 females (free Tri 21)

Risk Factors/CausesMaternal age

Age of 35, 1 in 385Age of 40, 1 in 106Age of 45, 1 in 30

DiagnosisPrenatal

AmniocentesisPUBSCVS

DiagnosisPostnatal

PHYSICAL EXAMINATION!

Diagnosis

Diagnosis

Karyotype FISH

Medical Issues

a LOT!

HEENT Issues

H: abnormal head shape, large fontanelles with delayed closure

E: congenital cataracts, “Brushfield spots”, congenital glaucoma, refractive errors, strabismus

E: hearing loss (78%), otitis

media (70%)

HEENT Issues

N: flat bridge, infections, midfacial hypoplasia OSA

T: cheilitis, malformed teeth, protruding tongue

NeckAtlantoaxial instability (14%)

Spinal cord compression (2%)

ThyroidHypothyroidism

1 in 141 vs. 1 in 4000Autoimmune thyroiditis (Hashimoto’s)Thyroid function testing

*DM, decreased fertility

Cardiac IssuesCongenital heart defects (60%)

Atrioventricular canal defect (45%)VSD (35%)Isolated ASD (8%)TOF (4%)Other lesions (1%)

GI IssuesCeliac Disease

4.6-7.1%Screening at 2-3yo

Neonatal JaundiceHirschprung’s DiseaseDuodenal atresia, imperforate anus, TE

fistula

Growth

GU Issues

HypospadiasCryptorchidismmicropenis

Extremity/Limb Issues

Acquired hip dislocations (6%)ClinodactylyArthritis (1-2%)

Hematologic Issues

Polycythemia in newborn (64%)Transient myeloproliferative disorder

(10%)ALL/AML

Skin Issues

XerosisAlopecia areata (10%)VitiligoFolliculitis, abscess formation

Neurologic IssuesSeizures (8%)

Bimodal onset: before 12 mos of age (40%) Infantile spasms, GTCPartial simple or complex seizures in adult

Moya Moya Syndromeprogressive narrowing and

occlusion of the intracranial

internal carotid arteries Collateral circulation

Behavior issues

Disruptive behavior, aggressive behavior (7%)

ADHD (6%)Conduct/ODD(5%)Autism (7%)

Developmental Progression

Milestones are achieved late, slower paceSitting at 11mosCreeping at 17mosWalking at 26mosFirst words at 18mos

Development in DS

No 2 patients are alikeVariabilities 2 to genetic, co-morbidities, child

rearing, social and education opportunitiesDS patients are individuals

Denver tool developed for DS patients (Chen & Wooley 1978)

Developmental milestones chart for DS(http://www.down-syndrome.org/information/development/early/?

page=7#milestones)

The spectrum of abilities in individuals with Down

syndrome

Development in DS

Social SkillsStrength, less delayed, socially sensitive,

responds to emotional cues, facial expressions

MotorDelayed but achieved, requires

help/supervision

Development in DS

Speech & Language SkillsDelayed than nonverbal understandingLearning to talk is most serious delay

Visual-SpatialVisual learners

Early Intervention

Better short and long term intellectual and social functioning

Most important focus of therapy should be development of expressive languageSigning, writing, printed reading materials

ResourcesSupport groups

References

http://www.down-syndrome.org/information/development/early

www.ds-health.comCapute G, et al. Down Syndrome,

Neurpdevelopmental disabilities in infancy and childhood, 3rd ed., p285-302, 2008

Thank you