Prenatal diagnosis of skeletal dysplasia is typically based on sonographic and radiological findings, and 3D-CT may be a valuable imaging tool complementary to ultrasonography for the diagnosis of FSD. However, it is necessary to select the appropriate sonography settings to minimize the degree of fetal irradiation without compromising image quality . In this study, we showed that when 3D-CT was used along with fetal ultrasonography, the prenatal diagnosis and definitive postnatal diagnosis differed in only one infant. This infant was diagnosed prenatally with FSD and postnatally with trisomy 21. However, when sonography was used without 3D-CT, prenatal diagnoses differed from definitive postnatal diagnoses in three infants. In addition, the pre- and postnatal classifications of the specific form of FSD differed in one infant. In this infant, the prenatal 3D-CT findings were the same as the postnatal X-ray findings. We were unable to identify ambiguous genitalia in the infant (a characteristic finding of CD)  on the fetal ultrasound examination. CD was subsequently diagnosed on the postnatal physical findings.
Fetal bone 3D-CT (as an auxiliary test for ultrasound examinations) has high diagnostic accuracy when performed at 26 weeks’ gestation and onward. The detection of abnormal findings outside the skeletal system on sonography can greatly affect the diagnosis [7, 8]. For an accurate diagnosis of FSD, both sonography and 3D-CT appear to be useful methods. In some cases, it can be difficult to differentiate skeletal dysplasia from a chromosomal abnormality. Of the 16 infants that underwent 3D-CT in our study, only one was suspected to have a chromosomal abnormality. In this case, skeletal dysplasia was suspected based on ultrasonography findings, but the results of 3D-CT suggested trisomy 21. Postnatal chromosomal testing was performed, resulting in a final diagnosis of trisomy 21 and the exclusion of this infant from the study. Some cases can be complicated, with concomitant skeletal dysplasia and a chromosome aberration. In particular, cases with combined ACH and trisomy 21 have been reported [9, 10]. ACH is a mild type of dysplasia in the group of FGFR3 abnormalities, where growing parts become hypoplastic due to endochondral ossification. This can be difficult to differentiate from trisomy 21 [9, 10]. In 2001  and 2014 , it was reported that femoral shortening during the second trimester is associated with a high relative risk of chromosomal abnormalities, particularly trisomy 21. If fetal femoral shortening is observed, it is important to consider the possibility of conditions such as chromosomal abnormalities, fetal growth restriction, and various other anomalies. Attention should also be paid to the presence of abnormal findings outside of the skeletal system (e.g., abnormalities in cardiac structure, the nervous/gastrointestinal system, and facial features) to reach a differential diagnosis. When making a prenatal diagnosis, it is important to bear in mind that cases of concomitant skeletal dysplasia and chromosomal abnormalities are possible, albeit rare.
Desbuquois dysplasia is a severe autosomal recessive disorder that belongs to the multiple dislocation group . It is characterized by shortened long bones, joint laxity, pre- and postnatal growth retardation, and progressive scoliosis. In the case of infant 12, the mother’s first child also had skeletal dysplasia (congenital dislocation of the knees) which was identified after birth. Although this child had been diagnosed with Larsen syndrome, it had neither been identified prenatally by sonography/3D-CT nor confirmed via postnatal genetic testing. The mother’s second child (infant 12), in contrast, received a prenatal ultrasound examination and 3D-CT, and was diagnosed with Desbuquois dysplasia, rather than Larsen syndrome. Postnatal genetic testing led to a definitive diagnosis of Desbuquois dysplasia (type 1), which is due to a mutation in the CANT1 gene [14, 15]. It is difficult to be diagnosed whether that it is Desbuquois dysplasia for clinical manifestations is Larsen syndrome. In the case of infant 12, it was demonstrated that an accurate prenatal diagnosis using an ultrasound examination and 3D-CT imaging was important to achieve a definitive diagnosis via postnatal molecular evaluation.
HPP is a condition in which tissue non-specific ALP loss or decrease causes abnormal bone and tooth mineralization . Many cases of HPP are inherited in an autosomal recessive, rather than an autosomal dominant manner. HPP can be classified into the following six clinical forms, which vary based on severity : 1) perinatal severe, 2) perinatal benign, 3) infantile, 4) childhood, 5) adult, and 6) odontohypophosphatasia. If parents have a child with HPP, they should be given genetic counseling with respect to future pregnancies, and the couple can decide whether to undergo carrier detection testing. If both the mother and father are carriers, the child has a 25% probability of being homozygous. Our fatal perinatal case appeared to be a severe one. The symptoms of perinatal cases appear early, resulting in intrauterine fetal death , stillbirth, or neonatal death.
Compared to normal fetuses, those with FSD are more likely to be in an abnormal fetal position owing to differences in physique, restricted posture, limited joint range of motion, and fractures . In cases of OI, it can be difficult to prevent intrauterine fractures as they can be caused by fetal movement (Fig. 5). Studies have shown that, in cases of OI, performing a cesarean delivery does not increase the frequency of fetal bone fractures compared to vaginal delivery . Moreover, in cases of the lethal type of OI, fetal survival does not appear to be affected by delivery mode (cesarean vs. vaginal delivery). For other types of skeletal dysplasias, the mode of delivery is often selected based on whether the condition is lethal. When the disease is diagnosed as lethal, a vaginal delivery may be selected even if the fetus is breech. However, in cases with marked head enlargement, a cesarean section is required regardless of whether the case is fatal, owing to the potential difficulty in passing through the mother’s pelvis. Prior to delivery, it is important for the parents, obstetrician, and pediatrician to discuss the plan for the resuscitation of the infant after birth. Accurate prenatal diagnosis is required to determine whether the case is fatal, and its degree of severity.
When considering the risk of radiation exposure, CT examination has not historically been the preferred method for pregnant women. However, in recent years, high-quality images adequate for a diagnosis have been made by low-dose 3D-CT, reducing the level of radiation to which the mother and fetus are exposed. The strength of this study was the accuracy of the prenatal diagnosis by 3D-CT scan in combination with fetal sonography. The limitation of this study is the relatively small sample size. Future studies should include a larger sample size to improve the power of the results. Continuation of this study is important in order to improve the diagnostic accuracy of fetal skeletal dysplasias.