Down Syndrome (Trisomy 21)

Last updated 03.11.12

 

Index

 

Definition

-  Abnormal genotype of (Aneuploidy) chromosome 21 with three copies (trisomy, triploid)

 

Features

-  Non-disjunction

-  Risk decreases with advancing gestation

-  Most M/C

-  10% 12-16/40

-  20% 16/40 to term

 

Risk Factors

-  Maternal age

-  1:1500 at 15-19yrs

-  1:890 at 30yrs

-  1:355 at 35yrs

-  1:90 at 40yrs

-  Risk 1/300 at 35 yrs

-  If previous fetus with Trisomy 21 risk = age +0.75%

-  Risk Calculation

-  (Age & gestation) x likelihood ratio by screening tests

 

Physical Appearance

-  Epicanthic folds

-  Single palmar crease

-  Wide nose

-  Low set ears

-  Curved 5th finger

-  Sandal gap

-  Brushfield spots (iris)

-  Large tongue

-  Hypospadius

-  Microdontia

-  Microcephaly

 

Associated Conditions

-  Congenital heart disease: VSD, ASD

-  Duodenal or oesophageal atresia

-  Atlanto-occipital/atlanto-axial instability

-  Hypotonia

-  Visual & hearing impairment

-  Mental retardation

-  Hypothyroidism

-  Leukaemia

-  10-20x risk

-  Typically <6 yrs (newborn or 3-6yrs)

-  Transient myeloproliferative disorder

-  Acute megakaryocytic leukaemia (AML)

-  Prematures senescence

-  Alzhiemers Disease: Dementia

-  Cataracts

-  OSA

 

Antenatal Screen

-  Offered to all pregnant women in Australia

-  To provide opportunity for TOP if high risk

-  Maternal Serum Screening (MSS)

-  Combined First Trimester Screening: blood test + US

-  Second Trimester Screening (Quad Test): blood test

-  Detection rates

-  70-80% with Age + NT

-  Increases to 85-90% with PAPP-A + free Beta hCG (Combined First Trimester Screening)

-  90% with Age + NT + NB

-  95% with Age + NT + NB + PAPP-A + free Beta hCG

-  Morphology Scan

-  No nasal bone 60-70%

-  No nuchal fold LR 10 (should be >6mm at 20/40)

-  Echogenic bowel LR 3

-  Short humerus LR 4.1

-  Short femur LR 1.6

-  Hydronephrosis LR 1.1

-  Echogenic focus in ventricle LR 1.1

 

Ix

-  High risk = >1:300 on Maternal Serum Screening

-  CVS = placental Bx

-  Performed at 11-13/40

-  1% M/C rate

-  Amniocentesis = fluid sample

-  Performed after 14/40

-  0.5% M/C rate

-  Karyotype takes 2-3 weeks

-  FISH takes 24hrs

 

Mx

-  Antenatal Dx: offer TOP

-  Dependant on gestation: suction D&C, D&E, misoprostol & labour

 

 

 

References

 

www.fetalmedicine.com/fmf/FMF-English.pdf