Ultrasonography

Ultrasonography is generally performed in the antenatal setting and in pregnant women whose fetuses are at risk for achondroplasia. Serial ultrasonography enables prenatal distinction between homozygous and heterozygous disease. ^[16, 17]

Homozygous achondroplasia results in rhizomelic micromelia, normal trunk length, and cloverleaf skull; these cases are lethal. Lung hypoplasia is a major cause of mortality (associated with thoracic narrowing). ^[18] There is a noticeable disproportion between skull dimensions and/or biparietal diameter (BPD) and limb lengths. The discrepancy between femoral length and BPD is noted as early as 13 weeks' gestation. The femoral length decreases to below the third percentile at 14.0-16.5 weeks' BPD age (mean, 15.6 wks). Therefore, femoral growth curves are established in the second trimester.

Heterozygous disease may not be recognized until late in the second trimester (>24-28 wk); early in the course of disease, ultrasonograms are normal. The changes in heterozygous achondroplasia are relatively mild and include short limbs, narrow thorax and abdomen, increased fetal head circumference and BPD, a protuberant forehead, and a diminished interpediculate distance in the spine. Rhizomelic limb shortening that predominantly affects the proximal long bones is observed.

Krakow and associates found that 3-dimensional (3-D) imaging in the prenatal-onset diagnosis of skeletal dysplasia had advantages over 2-dimensional (2-D) imaging in the evaluation of facial dysmorphism, relative proportion of the appendicular skeletal elements, and the hands and feet. ^[19] Of most importance, the patient and referring physician appreciated the 3-D images of the abnormal findings more readily than other images; this advantage aided in patient counseling and in managing the pregnancy. ^[20]

Patel and Filly retrospectively reviewed serial sonograms of 15 fetuses at 25% risk of homozygous achondroplasia. ^[21] Femoral growth curves were established and were compared with published standards to determine the gestational age. They were calculated according to BPD, at which femoral length crossed below the third percentile. The presence and severity of achondroplasia were clinically determined after birth.

Their results showed that the femoral length crossed the third percentile at 14.0-16.5 weeks BPD age (mean, 15.6 wk) in the 4 homozygous fetuses and at 18.2-26.2 weeks BPD age (mean, 21.5 wk) in the 8 heterozygous fetuses. In the 3 unaffected fetuses, femoral length did not cross percentiles as gestational age increased. The authors concluded that the establishment of a femoral growth curve in the second trimester with serial sonograms enables prenatal distinction between homozygous, heterozygous, and unaffected fetuses, when both parents have heterozygous achondroplasia.

Parilla and associates reported that the use of serial ultrasonographic scans to establish a femoral growth curve in the second trimester enables prenatal distinction between homozygous, heterozygous, and unaffected fetuses when both parents have heterozygous achondroplasia. ^[22] The investigators reviewed 37 cases of skeletal dysplasia diagnosed antenatally over 8 years, in which complete follow-up was available in 31 cases. The mean gestational age at diagnosis was 22.7 weeks (range, 14-32.3 wk). In 21 cases, the diagnosis was made before the 24th week. A final diagnosis was obtained in 80% of cases. The antenatal diagnosis was correct in 20 (65%) of 31 cases. Two false-positive diagnoses occurred. ^[22]

Specific final diagnoses included thanatophoric dysplasia (n = 8), osteogenesis imperfecta (n = 6), Roberts syndrome (n = 2), achondroplasia (n = 3), Ellis-van Creveld syndrome (n = 1), metaphyseal dysplasia (n = 1), spondyloepiphyseal dysplasia (n = 1), distal arthrogryposis (n = 1), caudal regression (n = 1), and glycogen storage disorder (n = 1). ^[22] The condition was correctly thought to be lethal in 16 of the fetuses on the basis of early, severe long-bone shortening (n = 13), femur length–abdominal circumference ratio of less than 0.16 (n = 12), hypoplastic thorax (n = 10), marked bowing or fractures (n = 4), short ribs (n = 4), caudal regression (n = 1), and cloverleaf skull (n = 1). The ability to predict lethality was 100%. No false-positive findings with respect to lethality occurred. ^[22]