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