Prenatal Diagnosis Of Skeletal Dysplasias Research Articles

Skeletal Dysplasia: A Case Report.

This paper presents a rare case of fetal hydrops detected at just 23 weeks of gestation in a 22-year-old woman's first pregnancy. The fetal ultrasound revealed severe skeletal anomalies, craniofacial deformities, and thoracic abnormalities, suggesting a complex and severe skeletal dysplasia, potentially type IA Achondrogenesis-a lethal autosomal recessive condition marked by ossification delay. This case highlights the significance of advanced genetic testing, such as next-generation sequencing (NGS) and whole-genome sequencing (WGS), in diagnosing and understanding skeletal dysplasias. Skeletal dysplasias represent a group of genetic disorders that affect osteogenesis. The prevalence of this condition is 1 in 4000 births. Sadly, 25% of affected infants are stillborn, and around 30% do not survive the neonatal period. There is a wide range of rare skeletal dysplasias, each with its own specific recurrence risk, dysmorphic expression, and implications for neonatal survival and quality of life. When skeletal dysplasia is incidentally discovered during routine ultrasound screening in a pregnancy not known to be at risk of a specific syndrome, a systematic examination of the limbs, head, thorax, and spine is necessary to reach the correct diagnosis. Prenatal diagnosis of skeletal dysplasia is crucial for providing accurate counselling to future parents and facilitating the proper management of affected pregnancies. An accurate diagnosis can be a real challenge due to the wide spectrum of clinical presentations of skeletal dysplasia but advances in imaging technologies and molecular genetics have improved accuracy. Additionally, some of these skeletal dysplasias may present clinical overlap, making it especially difficult to distinguish. After the 11th revision of genetic skeletal disorder nosology, there are 771 entities associated with 552 gene mutations. The most common types of skeletal dysplasia are thanatophoric dysplasia, osteogenesis imperfect, achondroplasia, achondrogenesis, and asphyxiating thoracic dystrophy.

Structured Reporting of Skeletal Survey in Skeletal Dysplasia

Skeletal dysplasia represents a big group of disorders with molecularly based skeletal abnormalities. These occur as a result of errors in skeletal development in utero, and the clinical spectrum of disease evolves and affects individual's life based on the lethality of the disorder. There are reported to be at least 400 different types of skeletal dysplasia in the scientific literature, most of which (owing to their rarity), we as radiologist may never come across our careers.[1] The naming and grouping of these disorders are ever changing, posing a further challenge to remember the details of each entity, often required for making a correct diagnosis. Diagnosis is often achieved through a combination of antenatal ultrasonography (where available), postnatal clinical examination, skeletal surveys, and genetic analysis. A multidisciplinary care forms the foundation for the management of an affected child.[2] Prenatal diagnosis of skeletal dysplasia remains challenging; however, in recent times, this certainly has seen an upswing. Some dysplasias display the same physical characteristics, yet are molecularly different, and vice-versa. Although no single unifying features exist, an evaluation of the various sonographic parameters can be performed that are helpful toward making a precise diagnosis.[3]

Prenatal diagnosis of recurrent moderate skeletal dysplasias in lamin B receptors.

The lamin B receptor (LBR) gene is located in chromosome 1q42.12 and encodes the lamin B receptor, an intracellular protein that binds to lamin B. LBR mutations are associated with a broad phenotypic spectrum ranging from non-lethal to lethal skeletal dysplasias. The typical phenotypes include the Pelger-Huet anomaly (PHA) and embryonic lethal Greenberg dysplasia (GRBGD). With the further study of this gene, other phenotypes have been found in different individuals. This retrospective study analyzed recurrent prenatal moderate skeletal dysplasias in Chinese fetuses. Nothing malformed was detected in the fetal karyotype and microarray, while the whole-exome sequencing identified a homozygous variant (NM_002296.4:c.1757G>A, NP_002287.2:p.Arg586His) in exon 14 of the LBR gene in both fetuses. Mutation analysis in the parents confirmed that the c.1757G>A variation is heterozygous by Sanger sequencing. Intensive analysis on bioinformatics and familial co-segregation suggest that the homozygous variation in the LBR gene is responsible for this recurrent prenatal moderate skeletal dysplasia. Moreover, moderate skeletal dysplasias differ from typical GRBGD phenotypes. Our findings are based on the DNA base test and the prenatal diagnosis of skeletal dysplasia, which can be helpful in proper phenotyping and contribute to a better understanding of the correlation between the phenotype and genotype.

Prenatal diagnosis of a novel pathogenic variation in the ACAN gene presenting with isolated shortening of fetal long bones in the second trimester of gestation: a case report

BackgroundHeterozygous mutations of the ACAN gene are a major cause of different evolutive growth defects in the pediatric population, but were never described as a cause of fetal skeletal dysplasia.Case presentationA G1 at 21w + 3d came to our institution for the second-trimester ultrasound and a skeletal dysplasia with prevalent involvement of limb’s rhizomelic tracts was suspected. Amniocentesis followed by CGH-array was performed, with normal results. An examination by NGS of some genes associated with skeletal dysplasias showed a novel pathogenic variant of the ACAN gene: c.2677delG.ConclusionSequence variations of ACAN were never described as a possible cause of fetal skeletal anomalies to date. In this case report, we describe the first prenatal diagnosis of skeletal dysplasia associated with a pathogenic variant of ACAN.

Diagnosing Fetal Skeletal Dysplasia Using Three-Dimensional Computed Tomography: A Study Protocol for an Interventional Study

Background: Fetal skeletal dysplasias are a group of skeletal dysplasias occurring during the fetal stage. As the use of fetal ultrasonography has become widespread, the rate of prenatal diagnosis of skeletal dysplasias has increased. However, many fetal skeletal dysplasia phenotypes have indistinct definitions, making definitive prenatal diagnosis difficult. Fetal imaging methods that are the basis of diagnosing fetal skeletal dysplasias include ultrasonography and three-dimensional computed tomography. The use of three-dimensional computed tomography requires specific imaging techniques and cannot easily be performed at all facilities. In the present study, we propose to conduct a survey for the preparation of a protocol with a low risk, and a high diagnostic accuracy. Methods: In total, 50 pregnant women who undergo three-dimensional computed tomography for the diagnosis of fetal skeletal dysplasias will be included. The primary outcome is prenatal diagnostic accuracy for fetuses with skeletal dysplasias. The secondary outcome is the safety from radiation exposure. Results and conclusion: Three-dimensional computed tomography should be considered for the prenatal diagnosis of fetal skeletal dysplasias, as it is important to judge whether the prognosis is favorable or lethal. When considering the risk of radiation exposure, high quality images that are adequate for a diagnosis have been obtained using low-dose three-dimensional computed tomography scans. This approach reduces the level of radiation to which the pregnant woman and fetus are exposed. Trial registration: University hospital Medical Information Network (UMIN) Center: Trial registration number is UMIN000034744. Data of registration is October 01, 2018. (URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039610)

Prenatal diagnosis of skeletal dysplasias using whole exome sequencing in China

BackgroundSkeletal dysplasias account for nearly 10% of fetal structural malformations detected by ultrasonography. This clinically heterogeneous group of genetic anomaly includes at least 461 genetic skeletal disorders with extreme clinical, phenotypic, and genetic heterogeneities, thus, significantly complicates accurate diagnosis. Researches have used whole exome sequencing (WES) for prenatal molecular diagnoses of skeletal dysplasias, however, data are still limited. MethodsDNA extracted from umbilical cord blood or amniocytes from fetuses suspected of skeletal dysplasias based on ultrasound evaluations were analyzed by WES. Blood samples were taken from the parents of the positive fetuses for co-segregation analysis using Sanger sequencing. ResultDefinitive molecular diagnosis was made in 6/8 (75%) cases, comprised of 5 de novo disease-causing changes in 3 genes (FGFR3, COL2A1, and COL1A2) and one proband with a biallelic deficiency for Lamin B Receptor(LBR),and including 3 novel variants. All fetuses had no detectable copy number variation (CNV) from sequencing results. ConclusionsOur study suggests that WES is an efficient approach for prenatal diagnosis of fetuses suspected of skeletal abnormalities and contributes to parental genetics counseling and pregnancy management.

Rapid prenatal diagnosis of skeletal dysplasia using medical trio exome sequencing: Benefit for prenatal counseling and pregnancy management.

The aim of this study is to explore the utility of rapid medical trio exome sequencing (ES) for prenatal diagnosis using the skeletal dysplasia as an exemplar. Pregnant women who were referred for genetic testing because of ultrasound detection of fetal abnormalities suggestive of a skeletal dysplasia were identified prospectively. Fetal samples (amniocytes or cord blood), along with parental blood, were send for rapid copy number variations testing and medical trio ES in parallel. Definitive molecular diagnosis was made in 24/27 (88.9%) cases. Chromosomal abnormality (partial trisomy 18) was detected in one case. Sequencing results had explained the prenatal phenotype enabling definitive diagnoses to be made in 23 cases. There were 16 de novo dominant pathogenic variants, four dominant pathogenic variants inherited maternally or paternally, two recessive conditions with pathogenic variants inherited from unaffected parents, and one X-linked condition. The turnaround time from receipt of samples in the laboratory to reporting sequencing results was within 2 weeks. Medical trio ES can yield very timely and high diagnostic rates in fetuses presenting with suspected skeletal dysplasia. These definite diagnoses aided parental counseling and decision making in most of cases.

A sonographic approach to the prenatal diagnosis of skeletal dysplasias.

Skeletal dysplasias are a heterogeneous group of conditions, many of which present unexpectedly in the prenatal period with a variety of ultrasound findings. Accurate prenatal diagnosis can now be facilitated using exome sequencing approaches, but in order to interpret results, accurate and detailed phenotyping is required. Here, we describe the sonographic approach to the prenatal diagnosis of skeletal abnormalities and illustrate how taking a systematic approach can facilitate diagnosis.

EP06.05: A retrospective study on prenatal diagnosis of skeletal dysplasias in Chinese

EP06.05: A retrospective study on prenatal diagnosis of skeletal dysplasias in Chinese

Prenatal diagnosis of skeletal dysplasias using a targeted skeletal gene panel.

This study aimed to perform an accurate and precise diagnosis for fetuses with suspected skeletal anomalies based on an incomplete and limited ultrasound phenotype. Proband-only targeted skeletal gene panel sequencing was performed on 12 families who had fetuses with suspected skeletal anomalies based on ultrasound evaluations at a mean gestational age of 24weeks and 3days. The fetuses all had normal standard genetic testing yield (karyotyping and microarray). In 10 of 12 fetuses, panel sequencing provided a diagnosis or possible diagnosis with identification of variants in the following genes: FGFR3, COL1A2, IHH, COL2A1, and DYNC2H1. Two cases revealed novel variants in COL2A1 and DYNC2H1. Our study suggests that targeted skeletal gene panel sequencing is highly sensitive for prenatal diagnosis of fetuses presenting with unexpected ultrasound findings suggestive of a skeletal dysplasia.

78: Multi-gene NGS panel yields high diagnostic rate of skeletal dysplasias detected by fetal ultrasound

Using a multi-gene panel designed for detection of 29 skeletal dysplasias known to manifest in the prenatal period, we aimed to determine (1) the diagnostic rate of the panel and (2) the ultrasound abnormalities that were associated with the highest diagnostic rate. Fetal specimens from 180 pregnancies referred for prenatal diagnosis for suspected skeletal dysplasia following abnormal ultrasound were tested. A custom designed NextGen sequencing panel interrogating the complete coding regions of 22 genes and 1 known pathogenic variant in IFITM5 was used. Of these tested genes, 7 are associated with autosomal dominant inheritance (AD), 12 with autosomal recessive (AR), 2 with AD/AR, 1 X-linked dominant and 1 X-linked recessive. Identification of pathogenic or likely pathogenic variant(s) (P/LP) consistent with gene and disease mechanisms was considered diagnostic. Physician-provided clinical indications were retrospectively reviewed and compared to the outcome of genetic testing. Prenatal testing provided diagnostic results in over half of fetuses (96/180; 53%) with causative variants identified in 10 genes associated with fetal skeletal dysplasias (FGFR3: n=43, COL1A1: n=15, COL1A2: n=11, COL2A1: n=10, SOX9: n=5, SLC26A2: n=4, DYNC2H1: n=3, FGFR2: n=3, EVC2: n=1, LEPRE1: n=1). The most common clinical test indications include short limbs, abnormal ribs/small chest circumference, bowed/fractured bones, and upper limb abnormalities. Of the negative or uncertain cases, 8% (7/84) were positive for concurrent or subsequent diagnostic testing (cytogenomic or whole exome sequencing). The diagnostic yield of our prenatal skeletal dysplasia panel was 53%. Among fetuses with a positive test outcome, 87 of 96 (91%) had an autosomal dominant disorder with 45% (43/96) of these in FGFR3 alone, and 9 of 96 (9%) an autosomal recessive disorder. Although these findings demonstrate genetic heterogeneity, four major ultrasound findings highly correlate with positive results for these distinct disorders. Our findings underscore the clinical utility of a comprehensive, multi-gene sequencing approach in the prenatal diagnosis of skeletal dysplasias.

Ultra-Low-Dose Fetal CT With Model-Based Iterative Reconstruction: A Prospective Pilot Study.

Prenatal diagnosis of skeletal dysplasia by means of 3D skeletal CT examination is highly accurate. However, it carries a risk of fetal exposure to radiation. Model-based iterative reconstruction (MBIR) technology can reduce radiation exposure; however, to our knowledge, the lower limit of an optimal dose is currently unknown. The objectives of this study are to establish ultra-low-dose fetal CT as a method for prenatal diagnosis of skeletal dysplasia and to evaluate the appropriate radiation dose for ultra-low-dose fetal CT. Relationships between tube current and image noise in adaptive statistical iterative reconstruction and MBIR were examined using a 32-cm CT dose index (CTDI) phantom. On the basis of the results of this examination and the recommended methods for the MBIR option and the known relationship between noise and tube current for filtered back projection, as represented by the expression SD = (milliamperes)-0.5, the lower limit of the optimal dose in ultra-low-dose fetal CT with MBIR was set. The diagnostic power of the CT images obtained using the aforementioned scanning conditions was evaluated, and the radiation exposure associated with ultra-low-dose fetal CT was compared with that noted in previous reports. Noise increased in nearly inverse proportion to the square root of the dose in adaptive statistical iterative reconstruction and in inverse proportion to the fourth root of the dose in MBIR. Ultra-low-dose fetal CT was found to have a volume CTDI of 0.5 mGy. Prenatal diagnosis was accurately performed on the basis of ultra-low-dose fetal CT images that were obtained using this protocol. The level of fetal exposure to radiation was 0.7 mSv. The use of ultra-low-dose fetal CT with MBIR led to a substantial reduction in radiation exposure, compared with the CT imaging method currently used at our institution, but it still enabled diagnosis of skeletal dysplasia without reducing diagnostic power.

Metatropic dysplasia in third trimester of pregnancy and a novel causative variant in the TRPV4 gene

Prenatal diagnosis of skeletal dysplasias is particularly difficult for many reasons and differentiating these disorders in the prenatal period can be challenging because they are rare and many of the ultrasound findings are not necessarily pathognomonic for a specific disorder. The diagnosis is often made just after birth or exitus. The prenatal diagnosis of osteochondrodysplasias is based predominantly upon fetal ultrasound findings and it focuses substantially on the possible lethality of the disorder, without always being able to find a specific name for the disorder.Metatropic dysplasia is a rare osteochondrodysplasia due to mutations in the TRPV4 gene: TRPV4 is a cation channel, non-selectively permeable to calcium, encoded by a gene on chromosome 12q24.11; it is widely expressed and involved in many different physiological processes through responses to several different stimuli (physical, chemical, and hormonal) in ciliated epithelial cells. The exact incidence of this disorder is not known, however less than a hundred cases have been reported at present, with only two prenatal reports but without any reference to the molecular test.We describe the first report of molecular diagnosis of metatropic dysplasia carried out in prenatal diagnosis: the molecular testing of the TRPV4 (transient receptor potential cation channel, subfamily V, member 4, MIM *605427) gene in our case, in fact, detected a causative variant, confirming the diagnostic suspicion, which was made possible thanks also to the utilization of MRI and CT scan. In our case different imaging methods together with the close cooperation of a multidisciplinary team and test availability, allowed an accurate diagnosis.

Non-Invasive Prenatal Diagnosis of Lethal Skeletal Dysplasia by Targeted Capture Sequencing of Maternal Plasma.

BackgroundSince the discovery of cell-free foetal DNA in the plasma of pregnant women, many non-invasive prenatal testing assays have been developed. In the area of skeletal dysplasia diagnosis, some PCR-based non-invasive prenatal testing assays have been developed to facilitate the ultrasound diagnosis of skeletal dysplasias that are caused by de novo mutations. However, skeletal dysplasias are a group of heterogeneous genetic diseases, the PCR-based method is hard to detect multiple gene or loci simultaneously, and the diagnosis rate is highly dependent on the accuracy of the ultrasound diagnosis. In this study, we investigated the feasibility of using targeted capture sequencing to detect foetal de novo pathogenic mutations responsible for skeletal dysplasia.Methodology/Principal FindingsThree families whose foetuses were affected by skeletal dysplasia and two control families whose foetuses were affected by other single gene diseases were included in this study. Sixteen genes related to some common lethal skeletal dysplasias were selected for analysis, and probes were designed to capture the coding regions of these genes. Targeted capture sequencing was performed on the maternal plasma DNA, the maternal genomic DNA, and the paternal genomic DNA. The de novo pathogenic variants in the plasma DNA data were identified using a bioinformatical process developed for low frequency mutation detection and a strict variant interpretation strategy. The causal variants could be specifically identified in the plasma, and the results were identical to those obtained by sequencing amniotic fluid samples. Furthermore, a mean of 97% foetal specific alleles, which are alleles that are not shared by maternal genomic DNA and amniotic fluid DNA, were identified successfully in plasma samples.Conclusions/SignificanceOur study shows that capture sequencing of maternal plasma DNA can be used to non-invasive detection of de novo pathogenic variants. This method has the potential to be used to facilitate the prenatal diagnosis of skeletal dysplasia.

Perinatal Diagnostic Approach to Fetal Skeletal Dysplasias: Six Years Experience of a Tertiary Center

Skeletal dysplasias (SDs) constitute a group of heterogeneous disorders affecting growth morphology of the chondro-osseous tissues. Prenatal diagnosis of SD is a considerable clinical challenge due to phenotypic variability. We performed a retrospective analysis of the fetal autopsies series conducted between January 2006 and December 2012 at our center. SD was detected in 54 (10%) out of 542 fetal autopsy cases which included; 11.1% thanatophoric dysplasia (n = 6), 7.4% achondroplasia (n = 4), 3.7% osteogenesis imperfect (n = 2), 1.9% Jarcho-Levin Syndrome (n = 1), 1.9% arthrogryposis (n = 1), 1.9% Dyggve-Melchior-Clausen syndrome (n = 1), 72.1% of dysostosis cases (n = 39). All SD cases were diagnosed by ultrasonography. In 20 of the cases, amniocentesis was performed, 4 cases underwent molecular genetic analyses. Antenatal identification of dysplasia is important in the management of pregnancy and in genetic counseling. Our data analysis showed that SD is usually detected clinically after the 20th gestational week. Genetic analyses for SD may provide early diagnosis and management.

Radiation dose reduction at MDCT with iterative reconstruction for prenatal diagnosis of skeletal dysplasia: preliminary study using normal fetal specimens.

The purpose of this study was to investigate to what degree the radiation dose can be reduced without affecting the ability to evaluate normal fetal bones at MDCT with iterative reconstruction. Fifteen normal fetal specimens immersed in containers (30- and 35-cm diameter) were scanned with a 64-MDCT scanner, with tube voltage of 100 kVp and tube current of 600, 300, 150, 100, and 50 mA. Images were subjected to adaptive statistical iterative reconstruction (ASIR). The fetal dose was measured using glass dosimeters. We calculated the relative ratio of the dose at 600 mA. Image quality was evaluated on maximum-intensity-projection and volume-rendering images. Two radiologists recorded the visualization scores of five regions. Images at 600 mA were considered to be standard. With the 30-cm-diameter container, the fetal dose was 10.15 mGy (relative ratio, 100%) at a tube current of 600, 51% at 300, 25% at 150, 17% at 100, and 9% at 50 mA. With the 35-cm-diameter container the fetal dose was 10.01 mGy (relative ratio, 100%) at 600, 47% at 300, 24% at 150, 17% at 100, and 8% at 50 mA. Visual evaluation showed that in both containers, with ASIR 90%, there was a statistically significant difference between 50-and 600-mA images (p<0.01) but not between 600-mA images and those acquired at 100, 150, and 300 mA (p=0.08-1.00). The fetal radiation dose for the evaluation of normal fetal bones can be reduced by 83% with ASIR 90%.

Novel c.358C&gt;T mutation of SOX9 gene in prenatal diagnosis of campomelic dysplasia

Novel c.358<scp>C</scp>&gt;<scp>T</scp> mutation of <i><scp>SOX</scp>9</i> gene in prenatal diagnosis of campomelic dysplasia

Low-Dose Fetal CT in the Prenatal Evaluation of Skeletal Dysplasias and Other Severe Skeletal Abnormalities

Prenatal diagnosis of skeletal dysplasia is often difficult and based on findings with ultrasound, a technique with 40-60% sensitivity. The purpose of this study was to evaluate a preliminary experience in assessing severe prenatal osseous abnormalities with low-dose fetal CT. The hypothesis was that use of CT may improve the prenatal diagnosis of skeletal dysplasia beyond the available capabilities of ultrasound. Retrospective search of a radiology database (July 2008-February 2011) yielded the records of unenhanced CT examinations of patients referred because of abnormal fetal bones. The original ultrasound and CT reports as interpreted at image acquisition were independently analyzed by two radiologists blinded to the final diagnosis and to the findings of the opposing imaging modality. Blinded review of the images was also performed. Correlation was made with the postmortem and postnatal findings. According to the reports of the studies, 5 of 21 cases were interpreted correctly with CT and incorrectly with ultrasound. In 17 cases, CT revealed additional osseous findings not in the ultrasound report. There were no cases in which ultrasound findings were correct and CT findings were incorrect. Blinded review of the images revealed that CT outperformed ultrasound (p < 0.001). There were a total of four CT errors among 218 total measures recorded and a total of 19 ultrasound errors among 218 total measures. Although low-dose fetal CT should never be used as the initial diagnostic modality in cases of suspected skeletal dysplasia, it is a powerful imaging adjunct that depicts the fetal bones in exquisite detail. Use of CT of fetuses at risk of skeletal dysplasia may provide clinicians with more accurate information for counseling of families regarding neonatal morbidity and mortality.

Early prenatal diagnosis of skeletal anomalies

To review experience of early prenatal diagnosis of skeletal dysplasias, and to explore diagnostic accuracy and improve management. A retrospective review of fetal medicine unit (FMU) records was performed to identify cases where a skeletal dysplasia was suspected by 14 weeks' gestation. A literature review was undertaken to ascertain cases with a diagnosis of a skeletal dysplasia in the late first or early second trimester. Fifteen cases were identified from review of FMU records, including ten different dysplasias with a variety of inheritance patterns. Accurate prenatal diagnosis was made only in cases with a positive family history, and in one case each of thanatophoric dysplasia and Roberts syndrome. Review of the literature identified further cases. Increased nuchal translucency was reported in other cases subsequently diagnosed as having a skeletal dysplasia. In early pregnancy, common presenting features included short femora, abnormal skull shape and mineralisation, profile or chest. Increasing use of first-trimester combined screening for Down's syndrome, with or without detailed anomaly scanning, will result in early detection of more skeletal dysplasias. Parents must be made aware that detailed postnatal pathological and radiological examination is usually required for accurate diagnosis and prediction of recurrence risks.

Prenatal diagnosis of short-rib polydactyly syndrome type 3 (Verma-Naumoff type) by three-dimensional helical computed tomography

We present a case of short-rib polydactyly syndrome (SRPs) type 3 in which accurate prenatal diagnosis was feasible using both ultrasonography and 3D-CT. SRP encompass a heterogeneous group of lethal skeletal dysplasias. However, the phenotypes overlap with those of nonlethal skeletal dysplasias (i.e. Ellis-van Creveld syndrome and Jeune syndrome). As accurate prenatal diagnosis of SRP is helpful for parents, we used 3D-CT in the early third trimester to examine a fetus suggested to have phenotypes of 'short-rib dysplasia group' on ultrasonography. 3D-CT showed mild modification of the vertebral bodies, small ilia with horizontal acetabula and triangular partial ossification defects, and subtle metaphyseal irregularities of the femora. These CT findings and an extensive literature search regarding the phenotypes of various diseases categorized as short-rib dysplasia group led to a correct prenatal diagnosis of SRP type 3. This case exemplified the usefulness of 3D-CT for the precise prenatal diagnosis of skeletal dysplasias.