18.1 Chromosomal & Genetic Abnormalities

Aneuploidy is an abnormal chromosome number, and most clinically recognized aneuploidies are trisomies — three copies of a chromosome instead of two. Second- and third-trimester sonography does not diagnose aneuploidy, but recognizable constellations of findings raise or lower the a priori risk and guide the offer of diagnostic testing.

Trisomy 21 (Down Syndrome)

Trisomy 21 is the most common autosomal trisomy in live-born infants, and its prevalence rises steeply with maternal age. Because roughly half of affected fetuses have no major structural defect, detection leans heavily on soft markers:

• Nuchal translucency (NT) >= 3 mm (or above the 95th percentile) at 11-14 weeks
• Nuchal fold >= 6 mm measured in the second trimester at the level of the cerebellum
• Absent or hypoplastic nasal bone on the midsagittal facial profile
• Echogenic bowel — bowel as bright as adjacent bone
• Echogenic intracardiac focus (EIF) — a bright dot in a cardiac ventricle, usually the left
• Short femur and short humerus relative to the biparietal diameter
• Mild ventriculomegaly (atrial diameter 10-12 mm) and renal pyelectasis

Structural associations include duodenal atresia (the double-bubble sign, present in about 30% of fetuses with trisomy 21) and atrioventricular septal (endocardial cushion) defects.

Trisomy 18 (Edwards Syndrome)

Trisomy 18 produces a long list of findings, and most fetuses show multiple anomalies plus early, symmetric intrauterine growth restriction (IUGR):

• Clenched hands with overlapping digits — the index finger overrides the third and the fifth overrides the fourth, and the hands rarely open
• Rocker-bottom feet with a prominent heel
• Choroid plexus cysts (also seen in normal fetuses, but persistent or multiple cysts in combination with other findings raise concern)
• Strawberry-shaped head — flattening of the occiput with frontal narrowing in the transverse axial view
• Omphalocele, congenital heart defects, and a single umbilical artery (SUA)

Trisomy 13 (Patau Syndrome)

Trisomy 13 is dominated by midline defects: holoprosencephaly (failure of forebrain cleavage), midline facial clefts with hypotelorism or a proboscis, and postaxial polydactyly. Echogenic, enlarged kidneys and cardiac defects are common.

Triploidy and Turner Syndrome

Triploidy (a 69,XXY or similar karyotype, usually from a double sperm contribution) causes severe, early asymmetric IUGR with marked head-to-body disproportion, syndactyly of the third and fourth digits, and partial molar changes in a large, cystic placenta when the extra set is paternal.

Turner syndrome (45,X) presents with a large, septated cystic hygroma in the posterior neck — often the largest neck mass seen in obstetric sonography — plus generalized non-immune hydrops. Associated findings include coarctation of the aorta and horseshoe kidney, and massive hygromas are usually lethal in utero.

Soft Markers Versus Structural Findings

A soft marker is a minor, often transient finding that is common in normal fetuses but statistically over-represented in aneuploidy. Soft markers — EIF, echogenic bowel, short femur, pyelectasis, choroid plexus cysts, thickened nuchal fold, absent nasal bone — do not damage the fetus; they only modify risk, each carrying a likelihood ratio that is multiplied into the patient's age- and serum-screen-based risk. An isolated soft marker in a low-risk patient usually requires no invasive testing. A structural anomaly is different: an omphalocele, holoprosencephaly, or major cardiac defect is itself abnormal and carries a substantial aneuploidy association, so counseling should include an offer of diagnostic testing — chorionic villus sampling (CVS) in the first trimester or amniocentesis after 15 weeks — with karyotype and chromosomal microarray.

Genetic (Non-Aneuploid) Conditions

Polycystic Kidney Disease

• Autosomal recessive polycystic kidney disease (ARPKD), also called infantile polycystic disease, produces bilaterally enlarged, diffusely echogenic kidneys from innumerable microscopic cysts, usually with oligohydramnios from poor urine output; severe cases progress to the Potter sequence with pulmonary hypoplasia.
• Autosomal dominant polycystic kidney disease (ADPKD) typically presents in adulthood, so the fetal kidneys often look normal; when visible prenatally, they are enlarged and echogenic but amniotic fluid usually remains normal because enough function is preserved. A family history is the key clue.

Skeletal Dysplasias

Skeletal dysplasias are evaluated with long-bone biometry — femur and humerus lengths plotted against gestational age — plus the chest circumference, because a small thorax predicts lethal pulmonary hypoplasia.

• Thanatophoric dysplasia is the most common lethal skeletal dysplasia: severe micromelia (all limb segments shortened), a narrow, bell-shaped thorax, platyspondyly (flattened vertebrae), bowed telephone-receiver femurs, and sometimes a cloverleaf skull.
• Achondroplasia is autosomal dominant (FGFR3 gene) and non-lethal: rhizomelic shortening (proximal segment, so the humerus and femur are shortest), frontal bossing, and a normal trunk length. Heterozygous cases may not show short limbs until the late second trimester.
• Osteogenesis imperfecta type II is the lethal perinatal form: multiple in utero fractures, bowed and angulated limbs, beaded ribs, and strikingly decreased skull mineralization, so the brain is seen unusually well and the skull compresses under transducer pressure.