Achondroplasia is the most common form of short-limbed dwarfism. The condition has been recognized since ancient times. Dwarfs were accepted socially in ancient Egypt, and their daily activities, recorded through art, suggest not only assimilation into daily life, but also in some cases, a high-ranking position in society (Kozma, 2006). The term achondroplasia, meaning total absence of cartilage, was first used by Parrot in 1878 (Scott, 1976). Although this is not correct in a pathologic sense, the designation is commonly accepted.

The incidence of achondroplasia is 1 in 26,000 livebirths (Oberklaid et al., 1979). Earlier studies that indicated an incidence of as high as 1 in 10,000 births probably included other causes of short-limbed dwarfism. More than 80% of cases are due to newmutations (Shiang et al., 1994). Advanced paternal age was initially thought to be correlated with an increased incidence of new mutations resulting in achondroplasia (Murdoch et al., 1970). However, more recent observations have led to the alternative theory that sperms bearing the fibroblast growth factor receptor 3 (FGFR3) mutation that causes achondroplasia have a selective advantage over sperms without this mutation (Horton et al., 2007).

Virtually all of the bones in the body are affected by achondroplasia. Postnatal radiographic studies of the lumbar spine, pelvis, and cranial regions permit definitive diagnosis (Figure 89-1). Antenatally, diagnosis is complicated by a relatively normal appearance until the early second trimester. The most consistent sonographic finding is shortening of the long bones, particularly the femur, occurring between 21 and 27 weeks of gestation (Figure 89-2) (Kurtz et al., 1986). The overall shape of the femurs is within normal limits. Initially, a normal relationship of biparietal diameter to femur is present, but these measurements become progressively asynchronous over time (Filly et al., 1981). Additional findings that have been described during the second trimester include large head (macrocrania), abnormal facial profile due to frontal bossing (Figure 89-3), protuberant abdomen, and trident-shaped hand (Figure 89-4) (Cordone et al., 1993).

For prenatal diagnosis in the setting of one parent affected with achondroplasia, the fetus is considered to be affected if the length of the long bones is less than the third percentile or if polyhydramnios is present (Lattanzi and Harger, 1982; Elejalde et al., 1983). If both parents are affected by achondroplasia, the fetus is at 25% risk of inheriting both mutant alleles. In a retrospective review of 15 fetuses at 25% risk of homozygous achondroplasia, Patel and Filly (1995) demonstrated that fetal femoral length dropped below the third percentile at a mean of 15.6 weeks and 21.5 weeks in fetuses with homozygous and heterozygous achondroplasia, respectively.

If both parents are unaffected, prenatal diagnosis is more challenging. A fetus in which long bone growth is initially normal but then drops below the 10th percentile during the third trimester needs to be serially evaluated for the possibility of achondroplasia or hypochondroplasia. Hypochondroplasia is considered to be an allele of achondroplasia, with less severe clinical manifestations.

Krakow et al. (2003) compared 2D and 3D imaging in the diagnosis of skeletal anomalies. In a case of achondroplasia, 3D imaging captured the trident hands and more clearly delineated the disproportionate aspects of the limbs. For example, the left arm raised to the fetal forehead demonstrated that the level of the elbow was at the chin instead of the nose due to foreshortening of the proximal part of the arm (rhizomelia).

In one case report, an increased nuchal translucency measurement was noted in a fetus that was subsequently confirmed by molecular diagnosis to have achondroplasia. Rhizomelia, narrow thorax, and macrocrania were not observed until 18 weeks (Tonni et al., 2005).

The most likely diagnosis for a fetus with shortened long bones is that the fetus is normal or has intrauterine growth restriction that is not due to a skeletal dysplasia. However, the differential diagnosis includes chromosomal abnormalities as well as other types of dwarfism, some of which may be lethal at birth. An important prenatal finding that distinguishes heterozygous achondroplasia from some of the other skeletal dysplasias is the initially normal first and second trimester long bone measurements.

Other considerations in the differential diagnosis include diastrophic dysplasia, a recessively inherited form of short-limbed dwarfism, with the additional findings of thickening of the external ear and the characteristic “hitch-hiker” thumbs (see Chapter 93). In achondrogenesis, a lethal, recessively inherited condition, there is deficient ossification of the vertebral bodies. As compared with achondroplasia, a greater discrepancy between head size and trunk exists in achondrogenesis (see Chapter 97). In chondroectodermal dysplasia (Ellis–van Creveld syndrome), progressive distal shortening of the extremities and postaxial polydactyly are present (see Chapter 94). In addition, congenital heart malformations are present in 50% of cases. In hypochondroplasia, the major findings are short stature and an increased upper-to-lower body segment ratio. The facial features are within normal limits.

Achondroplasia is due to mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. FGFR3 is a negative regulator of chondrocyte proliferation and differentiation in the growth plate. Mutations in the gene therefore activate the receptor and cause a gain of function (Horton, 2006). They predominantly affect bones that develop by endochondral ossification (Kurtz et al., 1986; Horton, 2006). Membranous bone formation occurs at a normal rate (Murdoch et al., 1970). The abnormality in achondroplasia is confined to cartilage, and consists of a failure of interstitial cells to proliferate. Bones that are initially formed from cartilage, such as the long bones of the extremities, bones at the base of the skull, and vertebral bodies are affected by this condition.

In histologic studies of bone and cartilage from patients with achondroplasia, morphology is normal (Rimoin et al., 1976). The arrangement of rows and columns of cells is regular and well organized. The rate of endochondral ossification is reduced and this contrasts with the normal periosteal ossification. This disparity results in periosteal bone extending beyond the growth plate and gives the appearance of short squat bones with cupped ends. Ultrastructural studies are also generally normal. The only abnormalities demonstrated have been a relative increase in the number of dead cells surrounded by microscars that contain focal aggregations of collagen fibrils (Rimoin et al., 1976).

For an unaffected pregnant woman, the antenatal course for this condition is usually benign. When achondroplasia is suspected, serial sonography may be useful to determine if macrocrania is developing, which may necessitate cesarean delivery.

For the pregnant woman affected with achondroplasia, special problems include increased incidence of fetal loss, preeclampsia, and respiratory compromise in the third trimester (Trotter et al., 2005). Baseline pulmonary function studies should be performed. Cesarean delivery is mandatory for cephalopelvic disproportion secondary to marked pelvic contracture (Lattanzi and Harger, 1982; Allanson and Hall, 1986).