Down Syndrome

syndrome is a variable combination of congenital malformations caused by trisomy 21. It is the most commonly recognized genetic cause of mental retardation Because of the morbidity associated with Down syndrome, screening and diagnostic testing for this condition are offered as optional components of prenatal care. Prenatal diagnosis of trisomy 21 allows parents the choice of continuing or terminating an affected pregnancy.

Etiology and Clinical Manifestations

Down syndrome is usually identified soon after birth by a characteristic pattern of dysmorphic features The diagnosis is confirmed by karyotype analysis. Trisomy 21 is present in 95 percent of persons with Down syndrome. Mosaicism, a mixture of normal diploid and trisomy 21 cells, occurs in 2 percent. The remaining 3 percent have a Robertsonian translocation in which all or part of an extra chromosome 21 is fused with another chromosome. Most chromosome-21 translocations are sporadic. AGE RELATED RISK A 20 year-old woman has a 1 in 1,500 risk of having a baby with Down's syndrome. A 30 year-old woman has a 1 in 800 risk. A 35 year-old woman has a 1 in 270 risk. A 40 year-old woman has a 1 in 100 risk. A 45 year-old woman has a 1 in 50 risk or greater.

Ultrasound
Ultrasound imaging can be used to screen for Down syndrome. Increased fetal nuchal translucency (NT) is an indicator of increased risk of Down syndrome. A 2003 systematic review of 30 studies of NT in Down syndrome found an average sensitivity of 75-80% with a false positive rate of 5.8-6% (95% confidence intervals).Therefore, while the false positive rate is too high for NT to be used alone as a screening test, it is useful as part of a combined test. Ultrasound measurement of NT is usually performed between 11 and 14 weeks gestation.

First and second trimester Down syndrome screens

Screen

When False Detection performed positive rate (weeks rate

Description

Combined test (Nuchal translucency/free beta-hCG/PAPP-A screen)

1013.5

85%

5%

Quad screen

1520

81%

5%

This test measures the maternal serum alphafetoprotein, unconjugated estriol, beta-hCG, andAlpha (INHA).

Integrated test

15-20

95

5%

The integrated test uses measurements from both the 1st trimester combined test and the 2nd trimester quad test to yield a more accurate screening result. Because all of these tests are dependent on accurate calculation of the gestational age of the fetus, the real-world false-positive rate is >5% and may be closer to 7.5%.

Incidence of Some Associated Medical Complications in Persons with Down Syndrome

DISORDER Mental retardation Growth retardation Early Alzheimer's disease INCIDENCE (%) > 95 > 95 Affects 75% by age 60 40

Congenital heart defects (atrioventricular canal defect, ventricular septal defect, atrial septal defect, patent ductus arteriosus, tetralogy of Fallot) Hearing loss (related to otitis media with effusion or sensorineural) Ophthalmic disorders (congenital cataracts, glaucoma, strabismus) reased nuchal fold thickness Cystic hygromas Echogenic intracardiac foci Congenital heart defects Increased intestinal echogenicity

40 to 75

60

RECURRENCE RISK AND FAMILY HISTORY

If a patient has had a trisomy 21 pregnancy in the past, the risk of recurrence in a subsequent pregnancy increases to approximately 1 percent above the baseline risk determined by maternal age. Diagnosis of a chromosome-21 translocation in the fetus or newborn is an indication for karyotype analysis of

both parents. If both parents have normal karyotypes, the recurrence risk is 2 to 3 percent. If one parent carries a balanced translocation, the recurrence risk depends on the sex of the carrier parent and the specific chromosomes that are fused.

Recommended additional monitoring of children with Down syndrome by DSMIG and CGAAP.

Test

Age

Hearing test

6 months, 12 months, then 1/year

T4 and TSH

6 months, then 1/year

Ophthalmic evaluation

6 months, then 1/year

Dental examination

2 years, then every 6 months.

Coeliac disease screening

Between 2 and 3 years of age, or earlier if symptoms occur.

Baseline polysommography

3 to 4 years, or earlier if symptoms of obstuuctive sleep apnea occur.

Cervical neck x-rays

Between 3 and 5 years of age