Ultrasound Detection of the Chromosomal Abnormalities DR. NABEEL BONDAGJI FRCSC, FACOG Associate Prof. Consultant King Abdulaziz University Hospital Consultant Perinatologist King Faisal Specialist Hospital & Research Center - Jeddah

Introduction  Spontaneous abortions  50% 50% trisomy 25% monosomy 10-15% mosaic Others  Stillbirths/neonatal deaths  6-11%  Live births  0.56% 1/3 autosomal, 1/3 sex xm, 1/3 other  In AMA patients undergoing amnio (2.26%) 64% trisomy, 17% sex xm, 19% other

Current Screening Methods  Advanced maternal age (AMA) ( 35 yrs)  Maternal serum screening (MSS, triple test. Free BHCG & Alpha HCG and the PAPPA  Family/personal history  Ultrasound

Diagnostic Methods 1. Amniocentesis  Early  Mid trimester 2. CVS 3. Cordocentesis 4. Fetal cells in the maternal circulation (experimental)

Frequency of aneuploidies vs the number of anomalies Number of anomalies PERCENTAGE

How Good is Ultrasound in Detecting Anomalies?  Chity et al BMJ nd trimester U/S 74% detection rate 87% severe anomalies  Lucle et al BMJ nd trimester U/S 87.5% detection 92.9% severe anomalies

Accuracy of Ultrasound in Detection of Chromosomal Abnormalities Variables: Trisomy %detection Trisomy 1385%detection Trisomy 2160%detection

Specific Chromosomal Abnormalities 1. Triploidy 2. Trisomy13 3. Trisomy18 4. Trisomy21 5. Monosomy 45 x 0 Turner S.

Trisomy 21 (Down Syndrome) ULTRASOUND ABNORMALITIES ASSOCIATED WITH DOWN SYNDROME 1. Nuchal translucency (nuchal edema) 40% of D.S. at 13 weeks 2. Thickened nucal fold 2 nd trimester 5-33% down 3. Ventriculomegally 4. Flattened facial profile 1:660 M:F1:1

5. Isolated pleural effusion 6. Congenital heart disease 50% of D.S. comment is endocardial cushion effect 7. Duodenal atresia 25% of Down (double bubble) 8.Ecogenic focus in the heart

9. Dilatation of the renal pelvis 10. Short femure : 0.91 of the expected femur length increase the rate of detection sensitivity 68%, specificity 98%. (Benacerraf)

11. Short humorous 12. Short fifth finger 13. The big toe separated from the rest (sandal sign) 14. Echogenic bowels  12.5% of Down babies +ve  5% folds increase in Down Syndrome

Prognosis  CHD – shorten the life span  GI Defect  I.Q. is limited  Hypotonia

First Trimester Nuchal Edema  Nicolaides et al (BMJ ’92)  827 women undergoing 1 st TM karyotyping  Nuchal edema: Subcutaneous translucency between skin and overlying tissue  3mm  51/827 (6%) cases had nuchal edema (3mm- 8mm)  Abnormal chromosomes 18/51 (35%) mainly T21)  Only 10/776 (1%) with no nuchal edema were chromosomally abnormal

First TM Nuchal Edema  Nuchal edema  3mm assoc with 10x risk for Xm abn  Mainly trisomies (T21) as in 2 nd TM NF  Sensitivity for T21 is approx 75%  Incidence of nuchal edema in normal is approx 4%

Pondya and Nicalaides Ultrasound in OB/GYN Amnio for Increasing Nuchal Translucency Thickness 3 mm3 times higher than expected on basis of age 4 mm18 times 5 mm28 times 6 mm36 times

Echogenic Bowel  Nyberg et al (Obstet Gynecol’91)  7% of T21 fetuses had echogenic bowel (2 nd TM)  Scioscia et al (Am J ’92)  6/19 (32%) of fetuses with echogenic bowel had Xm abn  5 T21, 1 T18 HOWEVER, 4/6 had other abnormalities  Crane et al  1/30 (3.3%) cases with echogenic bowel had T18

Fetal Cerebral Ventriculomegaly  Filly et al (’91): Posterior horns of lateral ventricles  GA independent (15-40 weeks)  Normal < 10mm (mean 6-7 mm)  Borderline mm (or mm)  Abnormal  15mm  Should be routinely measured at 18 week scan

Isolated Mild Ventriculomegaly  Summary of published cases (Achiron ’89-92)  Incidence of fetal trisomy: 11/92 (12%)  Spontaneous resolution in utero: 17 (18%)

Benacerraf and Group Scoring System Nucal Fold =2 Major structural defect =2 e.g. endocardial cushion, ompholocele, etc. Short femur & S = 1 Echogenic focus = 1 Pylactasis = 1 Echogenic Bowel = 1 Assoc with 2 or more will detect 81% of Down fetuses

TRISOMY 18 Incidence:1:3000 1:5000 M:F 1:3

Ultrasound Abnormalities  Limb abnormalities clenched hand and overlapping of the fingers Rocker-Bottom feet  Micrognethia  Congenital Heart Disease in 80% – VSD comment – TGV Fallot Tetralogy

choroid plexus cyst 25%  2-9% of CPC associated with trisomy 18 Omphalocele 25% Enlarged cisterna magna 15% Echogenic chordae tendaneai 35% Diaphragmatic hernia 30% associated of aneuploidy and the majority are 18%

The Posterior Fossa  Includes cerebellum and cisterna magna  Measures 1-10 mm (>10mm abnormal)  Abnormalities:  Dandy Walker malformation  Dandy Walker variant  Large cisterna magna (“Mega-cisterna magna”)

Large Cisterna Magna  Cisterna magna  10mm  Vermis intact, hydrocephalus usually absent  Nyberg et al (Obstet Gynecol\91)  33 fetuses cisterna magna > 10mm  Assoc anomalies 30/33 (90%)  Chromosome abnormalities 8/33 (55%)  T18 (12), T13 (3), other (3)  Correlated with absence of ventriculomegaly and presence of other anomalies

Prognosis: lethal poor prognosis 70% antenatal still birth 85% die in 1 st year all senses profound mental retardation - failure to thrive - hearing defect - visual difficulties - seizures

Ultrasound Abnormalities Associated with Trisomy 13  Single umbilical artery  Midline cleft, Cyclops(45%)  Microcephaly(12%) Incidence 1:50001:10000 Births

 Holoprosencephaly(40%)  polydactly and syndactaly  Scalp defect  A S D, VSD and hypoplastic left heart .agenesis of the corpus collosum

Holoprosencephaly  Failure of cleavage of pros encephalon  Alobar, semilobar and lobar  Assoc with facial defects (cyclope, proboscis, clefts)  Incidence of chromosome abnormalities: 40-60%  Usually Trisomy 13  Also trisomy 18, triploidy, 5p+, 13 q-,18p-.

Agenesis of Corpus Callosum  Associated with variety of Xm abnormalities  Trisomy 13, 18, 8, triploidy and translocations  Bertino et al (J U/S Med’87)  1/8 (14%) with fetus with agenesis CC: Trisomy 8

Prognosis Lethal Poor Prognosis  50% dies 1 st two months  90% dies 1 st year  Survivors will develop profound mental retardation

Ultrasound Abnormalities Associated with Triploidy  Severe IUGR (early onset)  Oligohydramnios  Molar degeneration of the placenta  Holoprosencephaly & agenesis CC Prognosis:lethal antenatally mosaicM.R.

Turner Syndrome Ultrasound Abnormalities  Cystic hygroma 90% of Turner  CHD aortic coarctation  Renal agenesis & pelvic kidney and horse shoe kidney  Hydrops fetalis 1:50001:1000

Prognosis: With hydrops mortality approaches 100% survivor:  Degree of CHD  Hearing defect 50%  Absence of 2 nd sexual character and infertility  Skeletal growth retardation  Normal intelligence

Nuchal Cystic Hygroma  Azar et al (Fetal Diag Ther ’91)  Abnormal chromosomes: 75%  Turner’s syndrome (45 x0): 94%  Assoc CHD 48%, renal 20%, abn biometry 90%  Normal chromosomes: 25%  Associated abnormalities: 75%  Live born healthy: 2-3%

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