At our institution chorionic villus sampling and foetal echocardiogram are provided when a nuchal translucency greater than the 95th percentile is found. On confirmation of major genetic or structural anomalies, termination of pregnancy is offered and foetal autopsy performed. A foetal radiography is also included before pathological examination.

In a five-year period, two hundred and nineteen cases where nuchal translucency was greater than the 95th percentile were reviewed and radiological-pathological correlation performed on pregnancy termination cases.

From this research we selected a series of cases and individual anomalies, which are described in the next section. The cases accompany a summary of the most common pathologic changes encontered in specific syndromes encountered.

Down syndrome

Incidence: 1/500

Etiology : trisomy of chromosome 21 or Robertsonian translocation (5%)

Associated ecographic anomalies:

First trimester:

- increased NT / cystic hygroma

- absent / short nasal bone

- altered ductus venosus Doppler spectrum

- bowel atresias (e.g. esophageal atresia, duodenal atresia)

- exomphalos

Second trimester:

- nuchal fold (>5mm)

- small or dysplastic ears

- heart defects (e.g. ventricular septum defect, ventriculomegaly)

- intracardiac ecogenic foci

- aberrant right sub-clavian artery

- short femur

- short humerus

- echogenic bowel

- pyelectasis

- hypoplasia of the middle phalanx of the fifth digit

- “sandal gap”

Fig. 6: Down syndrome case terminated at 15 weeks. Ultrasound, radiographic and pathologic examinations revealed a lange cystic higroma (arrows) associated with diffuse subcutaneous thickening and pulmonary edema (long arrow). This exquisite appearance was believed to be secondary to congenital cardiac anomalies, notice an absent a wave at ductus venosus flow spectrum (spaced Doppler complexes). Other findings can be appreciated: "sandal gap" sign (left foot) and calcified/echogenic bowel loops (arrow heads). Flexed limbs suggesting arthrogryposis.
References: CGC Genetics and Centro Hospitalar de Vila Nova de Gaia e Espinho

Fig. 7: Foetal radiography (lateral view) of a 13 week fetus with Down syndrome. Note de thickened nuchal soft tissues (short arrows) and the absent nasal bones (asterisk). One can also apreciate a right sided club foot deformity (long arrow).

Fig. 8: A case of Down syndrome, terminated at 15 weeks. Lateral radiography where serpiginous calcified meconium is highlighted. Nuchal soft tissue prominence (asterisk).

Edwards syndrome

Incidence: 1/6000

Etiology: trisomy of chromosome 18 and rare cases of mosaicism or chromosome 18 anomalies

Associated ecographic anomalies:

- Nervous system anomalies (neural tube defects, agenesis of corpus callosum, posterior fossa, choroid plexus cysts)

- Cystic hygroma

- Micrognathia

- Foetal growth restriction

- Kidney anomalies (e.g. renal dysplasia, horseshoe kidney)

- Clenched hands

- Rocker bottom foot

- Radius aplasia

- Strawberry-shaped skull

Fig. 9: Edwards syndrome at 14 weeks. The main anomalies identified were growth restriction (biometric evaluated as 12 weeks), omphalocele (long arrows), iliac bone dysplasia (arrow head) and absent nasal bone (short arrow).

Fig. 10: Edwards syndrome - frontal and lateral foetal radiography, aplasia radii of the left limb (arrow), bilateral club feet and clenched hands.

Patau syndrome

Incidence: 1/12000

Etiology: trisomy of chromosome 13 and robertsonian translocations (25%)

Associated ecographic anomalies:

- Cystic hygroma

- Microcephaly

- Holoprosencephaly

- Ocular malformations

- Facial clefts

- Neural tube defects

- Congenital heart disease (septa defects, pulmonary venous return, intracardiac foci…)

- Polydactyly

- Exomphalos

- Renal dysplasia

- Foetal growth restriction

Fig. 12: Patau syndrome terminated at 18 weeks - growth retardation, facial cleftings (arrows) and cystic hygroma (arrow heads) can be appreciated.
References: CGC Genetics and Centro Hospitalar de Vila Nova de Gaia e Espinho

Turner syndrome

Incidence: 1/2000 to 1/5000

Etiology: monossomy of chromosome X due to loss of paternal X chromosome and mosaic forms

Associated ecographic anomalies:

- Large volume cystic hygroma (larger than other karyotypic anomalies)

- Extensive and early foetal hydrops due to diffuse malformations of the lymphatic system
- Hypoplastic left heart 
- Aortic coarctation
- Horseshoe kidney

Fig. 11: Turner syndrome at 12 weeks of pregnancy - note the large cystic hygroma at the cranium base plane (long arrows), extending caudally as diffuse subcutaneous thickening (arrow heads). Also notice the bilateral pulmonary edema.

Beckwith-Wiedemann syndrome

Incidence:  1/13000 to 1/37000

Etiology: Genetic anomalies related to 11p15.5 regulation of gene transcription, with 15% having family history.

Associated ecographic anomalies:

- Abdominal wall defects 

- Macroglossia 

- Micrognathia

- Macrossomia 

- Hemihyperplasia 

- Visceromegaly (one of the few cases of in-utero hepatomegaly) 

- Renal anomalies

- Cardiac anomalies 

- Polyhydramnios and increased placental thickness

- Embryonal tumors (usually after birth, Wilms tumor most commonly)

Fig. 13: Beckwith-Wiedemann syndrome - large protruding tong (arrows); hepatomegaly seen at different levels (asterisks) and macrossomic aspect of the fetus, notice the overdeveloped muscles of the upper limb (arrow heads).
References: CGC Genetics and Centro Hospitalar de Vila Nova de Gaia e Espinho

Cat-Eye syndrome 

Incidence: 1/50000 to 1/150000

Etiology: partial tetrasomy trisomy of the 22pter-22q11 chromosomic regions.

Associated ecographic anomalies:

- Coronary anomalies (++pulmonary return)

- Pre-auricular tags

- Anorectal atresia

- Urologic and genital anomalies

- Ear deformities

Fig. 14: Cat-Eye syndrome - termination of pregnancy at 24 weeks. Pre-auricular tags and anal atresia with intestinal malrotation were found. At ultrasound examinations (transverse plane at the pelvis level), dilated bowel loops were observed (arrows). Normal sized urinary bladder (asterisk). At the fetal radiography 13 ribs can be counted bilaterally.
References: CGC Genetics and Centro Hospitalar de Vila Nova de Gaia e Espinho

 Unkown syndromes 

During our research we found four cases where the genetic study (karyotype and array CGH) and the sum of ecographic and pathologic anomalies were not sufficient to conclude a specific diagnosis.

In these cases, further investigation is possible thru exome sequencing. This technique was suggested but not followed.

The last case we present was referenced to our center due to increased nuchal translucency (7mm), detected on the first trimester ultrasound. Chorionic villus sampling didn’t reveal any chromosomic anomalies (46, XY) and CGH array was normal.

On follow up examinations (second trimester ultrasound), foetal echocardiography  (20weeks) was performed, which revealed a complex cardiac malformation, bilateral pielectasis and dilated bowel loops.

The cardiac examination diagnosed double outlet from the right ventricle (pulmonary e aorta arteries) associated with markedly pulmonary hypoplasia and atrial septal defect (described as a coronary sinus type at autopsy) e sub-valvular ventricular septal defect.

Pregnancy termination was performed at 22 weeks, based on the gathered malformations.

The foetal radiograph and pathologic examination confirmed the sonographic findings and allowed to identify additional anomalies, such as imperforated anus with associated megacolon and rectum stenosis or atresia, micropenis with hypospadias, rocker-bottom feet and clinodactyly (fingers 3, 4 and 5) of both hands.

Fig. 15: Undetermined syndrome - lateral radiographic view and macroscopy photography. Arrow heads indicate the presence of "rocker-bottom" feet.
References: CGC Genetics and Centro Hospitalar de Vila Nova de Gaia e Espinho

Fig. 16: Cardiac malformation - foetal ecocardiography (A to D) A - auriculo-ventricular concordance and a large sub-valvular ventricular septum defect (arrow); B - hypoplastic pulmonary artery (arrow); C and D aorta (ao) originating from de right ventricle (vd)(ve - left ventricle); E and F autopsy specimens confirming the ultrasound findings.
References: CGC Genetics and Centro Hospitalar de Vila Nova de Gaia e Espinho

Fig. 17: Undetermined syndrome 22 weeks - bilateral pyelectasis (ultrasound image - transverse plane at the abdomen). Dilated urethers (arrow heads), lobulated asymmetric kidneys, micropenis with hypospadias and anal atresia (small arrow) with dilated bowel loops (large arrow) were visualised at autopsy.
References: CGC Genetics and Centro Hospitalar de Vila Nova de Gaia e Espinho