Prenatal Musculoskeletal Imaging

Etiology.

Dysplasias are often the result of genetic mutations that encode for proteins important to development of the growth plate. Current clinical application of “skeletal dysplasia testing panels” is, however, very limited. Both the range of included mutations and the sensitivities of their detection are expected to increase with time. Furthermore, the discovery of cell-free fetal DNA in maternal plasma may lead to noninvasive techniques such as capture sequencing for the prenatal diagnosis of some skeletal dysplasias. In utero testing in sporadic cases remains controversial.

Imaging.

More than 430 dysplasias have been described in the literature. Only a small percentage is considered diagnosable in utero with imaging. Because of the lack of specificity of many of the findings, efforts at ultrasonographic prenatal evaluation have focused on identification of cases in which the neonates are not expected to survive, typically because of an abnormally constricted chest ( Box 130.1 ). Most of these criteria correlate limb length with survival, but emphasis is also placed on measures predicting lethal pulmonary hypoplasia. Other findings that may be detected in association with lethality and that increase diagnostic certainty are polyhydramnios and nonimmune hydrops fetalis. It is important to avoid making a diagnosis of lethality in borderline cases and to use criteria in combination for the most accurate discrimination. The fetus with intrauterine growth retardation should not be assigned a diagnosis of generalized skeletal dysplasia on the basis of proportionate but short bones. Questionable cases in either category deserve follow-up ultrasonography for interval growth.

Three dysplasias constitute the vast majority of lethal cases: (1) thanatophoric dysplasia, (2) achondrogenesis, and (3) osteogenesis imperfecta type II. A familiarity with their ultrasonographic features is therefore essential ( Box 130.2 ).

Certain morphologic findings on ultrasonography suggest particular diagnoses in the setting of a suspected dysplasia. Multiple long bone fractures are very likely from osteogenesis imperfecta or hypophosphatasia, and rib fractures are rarely seen with other diagnoses ( Fig. 130.1 ). Kleeblattschädel, or cloverleaf skull, may be present in several of the acrocephalosyndactyly syndromes (Apert, Carpenter, Crouzon, and Pfeiffer syndromes), campomelic dysplasia, osteocraniostenosis, and thanatophoric dysplasia type II ( Fig. 130.2 ). Hypoplastic scapular bodies are a feature of campomelic dysplasia and Antley-Bixler syndrome. However, many findings (e.g., platyspondyly, short ribs) are not specific and must be considered in relation to other features (abnormal mineralization, solid organ malformations) to arrive at a more narrow differential diagnosis ( e-Fig. 130.3 and Fig. 130.4 ). Three-dimensional ultrasonography can be very helpful when an appropriate volume of fluid is present around the fetus to display the morphology of specific segments, including the face, hands, and feet.

Fetal MRI has not been pursued routinely in the evaluation of fetal dysplasia because of the difficulty in imaging the signal-poor ossified skeleton. However, it may have a role in quantification of fetal lung volumes in cases in which ultrasonography has limitations. It has also been used successfully to make the diagnosis of dysplasias that primarily involve the epiphyses, taking advantage of the high water content T2-weighted signal characteristics of cartilage ( e-Fig. 130.5 ). Finally, fetal magnetic resonance imaging (MRI) specifically for temporal lobe malformation evaluation has been used when an FGFR3 mutation expression (such as thanatophoric dysplasia) is suspected.

The use of ionizing radiation is generally avoided during pregnancy unless the need to make a diagnosis is critical to patient care, though low-dose CT techniques have been used effectively to reconstruct highly detailed three-dimensional models of the fetal skeleton ( Fig. 130.6 ). The features described are compared with an atlas of postmortem radiographs in identified syndromes to aid diagnosis. This strategy can be offered at radiation doses of 3 to 5 millisievert with superb resolution of individual skeletal components.

Treatment and Follow-up.

When a lethal skeletal dysplasia is detected using ultrasonography, the parents and fetal care team can make informed decisions about the continuation of the pregnancy and the circumstances of delivery. An opportunity exists for neonatal hospice care coordination, when appropriate. Even though ultrasonography is reliable at separating lethal dysplasias from nonlethal dysplasias, neonatal physical examination and radiographs, appropriate genetic testing, and autopsy, if relevant, are crucial in arriving at a specific diagnosis for accurate family counseling.