TRISOMY 21- DOWN SYNDROME

IncidenceApproximately one in 1000 live births.

GeneticsTrisomy 21 (47, +21), - 94 %, The frequency of trisomy increases with increasing maternal age.Robertsonian translocation involving chromosome 21- Approx. 3-4 %, not related to maternal age.Trisomy 21 mosaicism 2 to 3 % cases

Clinical FeaturesHead and neckBrachycephalyUp-slanting palpebral fissuresEpicanthal foldsBrushfield spotsFlat nasal bridgeFolded or dysplastic earsOpen mouthProtruding tongueShort neck Excessive skin at the nape of neckExtremitiesShort broad handsShort fifth fingerIncurved fifth fingerTransverse palmer creaseSpace between first and second toeHyper flexibility of joints

Neonatal featuresFlat facial profilePoor Moro reflexExcessive skin at the nape of neckSlanted palpebral fissuresHypotonia Hyper flexibility of jointsDysplasia of pelvisAnomalous earsDysplasia of midphalanx of fifth fingerTransverse palmer crease

Mental RetardationAlmost all DS babies have MR.Mildly to moderately retarded .Starts in the first year of life.Average age of sitting(11 mon), and walking (26 mon) is twice the typical age.First words at 18 months.IQ declines through the first 10 years of age, reaching a plateau in adolescence that continues into adulthood.

Heart Disease50 % of Down Syndrome pts have heart diseaseAtrioventricular septal defectVSDSecundum ASDPDATetrology of FallotMitral valve prolapseAR, MR

GI abnormalities5% of casesDuodenal atresia or stenosis, sometimes assoc with annular pancreas in 2.5 % of casesImperforate anusEsophageal atresia with TE fistula is less commonHirschsprungs diseaseStrong assoc with celiac disease b/w 5 16 % , 5 16 fold increase as compared to general population

GrowthBW, length and HC are less in DS Reduced growth ratePrevalence of obesity is greater in DSWeight is less than expected for length in infants with DS, and then increases disproportion ally so that they are obese by age 3-4 yrs

Eye problems Most common disorders are Refractory error 35 to 76 percent Strabismus 25 to 57 percent Nystagmus 18 to 22 percent Cataract occur in 5 % of newborns. Frequency increases with age.

Hearing lossUnilateral or bilateralConductive, sensorineural or mixedOtitis media is a frequent problem

Hematologic disordersThe risk of leukemia is 1 to 1.5 percent.65% of newborn have polycythemia resulting in hypoglycemia.Risk of AML and ALL is also much higher than the general population.Transient leukemia exclusively affects NB. - It is asymptomatic with spontaneous resolution in 2-3 months. - Vesiculopustular skin eruptions are common and resolve with disorder.

Endocrine disorderThyroid disease Hypothyroidism occurs more frequently than hyperthyroidism.Diabetes The risk of type 1 diabetes is three times greater than that of the general population.

ReproductionWomen with DS are fertile and may become pregnant.Nearly all males with DS are infertile. The mechanism is impairment of spermatogenesis

Atlantoaxial instabilityExcessive mobility of atlas (C1) and the axis (C2), may lead to subluxation of the cervical spine. Diagnosis made by lateral neck radiograph.Patients are advised to avoid contact sports.

Sleep apneaObstructive sleep apnea is more common.

Skin disorderPalmoplantar hyperkeratosisSeborreic dermatitisFissured tongueCutis marmorataGeographical tongueXerosis

DiagnosisPrenatal screeningIf no screening It is recognized from the characteristic phenotypic features.Confirmed by Karyotype.

Management1. Growth Measurements should be plotted on the appropriate growth chart for children with DS.This will help in prevention of obesity and early diagnosis of celiac disease and hypothyroidism.

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

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

Management (cont.)4. 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.

5. Thyroid Function Should be done in newborn period and should be repeated at six and 12 months , and then annually.

6. Celiac Disease Screening should begin at 2 yrs. Repeat screening if signs/Sx develop.

Management ( cont)Hematology CBC with differential at birth to evaluate for polycythemia as well as WBC.

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

Alzheimers disease Adult with a Down Syndrome has earlier onset of symptoms. When diagnosis is considered, thyroid disease and possible depression should be excluded.

MortalityMedian age of death has increased from 25 yrs in 1983 to 49 yrs in 1997, an average of 1.7 yrs increase per year.

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

Improved survival is because of increased placements of infants in homes andchanges in treatment for common causes of death.

Survival is better for males and blacks.

CounselingMay begin when a prenatal diagnosis is made.Discuss the wide range of variability in manifestation and prognosis.Medical and educational treatments and interventions should be discussed.Initial referrals for early intervention, informative publications, parent groups, and advocacy groups.