Prenatal Assessment of the Position of Fetal Conus Medullaris as a Predictor of Fetal Spinal Lesions.

OBJECTIVES: The aim of this study is to compare two different methods in assessment of the position of fetal conus medullaris (CM) and to explore the significance for assessment of CM. METHODS: This study included both normal fetuses and those with the diagnosis of fetal spinal lesions. The position of fetal CM was performed sonographically using two methods: location of CM in relation to the vertebral body (CM level) and measurement of the conus sacrum (CS) distance. RESULTS: The results showed that intra-observer and interobserver concordance was high for the two methods, both in the normal and abnormal groups. There was significant association between femur length and CS distance (R2 = 0.917) and between gestational age and CS distance (R2 = 0.892). CONCLUSIONS: We propose the combined use of CM level location and CS distance measurement for the prenatal diagnosis of fetal spinal lesions for complementary needs.

Vertebral cross-sectional area: an orphan phenotype with potential implications for female spinal health.

A high priority in imaging-based research is the identification of the structural basis that confers greater risk for spinal disorders. New evidence indicates that factors related to sex influence the fetal development of the axial skeleton. Girls are born with smaller vertebral cross-sectional area compared to boys-a sexual dimorphism that is present throughout life and independent of body size. The smaller female vertebra is associated with greater flexibility of the spine that could represent the human adaptation to fetal load. It also likely contributes to the higher prevalence of spinal deformities, such as exaggerated lordosis and progressive scoliosis in adolescent girls when compared to boys, and to the greater susceptibility for spinal osteoporosis and vertebral fractures in elderly women than men.

Cervical spine synostosis: an anatomical study with emphasis on embryological and clinical aspects.

PURPOSE: The objectives were to study the anatomical features of fused vertebra in the cervical region. MATERIALS AND METHODS: The study included 363 cervical vertebras which were macroscopically observed for the fusion and their morphology was studied. RESULTS: Among our specimens, one fusion was observed between the C1 and C2 and the other was between C2 and C3. The mean anteroposterior diameter of normal atlas and axis were 42.1 +/- 0.9 mm and 46 +/- 0.5 mm respectively. The fused C1-C2 had 39 +/- 0.6 mm anteroposterior diameter. The mean lengths of anterior arch of normal atlas and body of axis were 16 +/- 0.9 mm and 23 +/- 0.7 mm respectively and the fused C1-C2 body length was 30 +/- 0.3 mm. The mean anteroposterior diameter of normal C2 and C3 vertebra were 46 +/- 0.5 mm and 47 +/- 0.8 mm respectively and of fused C2-C3 was 44 +/- 0.2 mm. The body length of C2 was 23 +/- 0.7 mm and C3 was 33 +/- 0.1 mm. The body length of fused C2-C3 was 36 +/- 0.8 mm. CONCLUSION: The present study has provided additional information on the anatomy, morphology of cervical spine synostosis with their embryological basis and clinical implications.

The mouse notches up another success: understanding the causes of human vertebral malformation.

The defining characteristic of all vertebrates is a spine composed of a regular sequence of vertebrae. In humans, congenital spinal defects occur with an incidence of 0.5-1 per 1,000 live births and arise when the formation of vertebral precursors in the embryo is disrupted. These precursors (somites) form in a process (somitogenesis) in which each somite is progressively separated from an unsegmented precursor tissue. In the past decade the underlying genetic mechanisms driving this complex process have been dissected using animal models, revealing that it requires the coordinated action of at least 300 genes. Deletion of many of these genes in the mouse produces phenotypes with similar vertebral defects to those observed in human congenital abnormalities. This review highlights the role that such mouse models have played in the identification of the genetic causes of the malsegmentation syndrome spondylocostal dysostosis.

Fetal spinal anomalies in a first-trimester sonographic screening program for aneuploidy.

OBJECTIVES: To review the sonographic features of spinal anomalies in first-trimester fetuses presenting for screening for chromosomal abnormalities. METHODS: Fetuses with a spinal abnormality diagnosed prenatally or postnatally that underwent first-trimester sonographic evaluation at our institution had their clinical information retrieved and their sonograms reviewed. RESULTS: A total of 21 fetuses complied with the entry criteria including eight with body stalk anomaly, seven with spina bifida, two with Vertebral, Anal, Cardiac, Tracheal, Esophageal, Renal, and Limb (VACTERL) association, and one case each of isolated kyphoscoliosis, tethered cord, iniencephaly, and sacrococcygeal teratoma. One fetus with body stalk anomaly and another with VACTERL association also had a myelomeningocele, making a total of nine cases of spina bifida in our series. Five of the nine (56%) cases with spina bifida, one of the two cases with VACTERL association, and the cases with tethered cord and sacrococcygeal teratoma were undiagnosed in the first trimester. Although increased nuchal translucency was found in seven (33%) cases, chromosomal analysis revealed only one case of aneuploidy in this series. CONCLUSIONS: Fetal spinal abnormalities diagnosed in the first trimester are usually severe and frequently associated with other major defects. The diagnosis of small defects is difficult and a second-trimester scan is still necessary to detect most cases of spina bifida.

Transgenic over-expression of growth differentiation factor 11 propeptide in skeleton results in transformation of the seventh cervical vertebra into a thoracic vertebra.

Growth differentiation factor 11 (GDF11) is one of the significant genes that control skeletal formation. Knockout of GDF11 function causes abnormal patterning of the anterior/posterior axial skeleton. The mRNA of GDF11 is initially translated to a precursor protein that undergoes a proteolytic cleavage to generate the C-terminal peptide or mature GDF11, and the N-terminal peptide named GDF11 propeptide. The propeptide can antagonize GDF11 activity in vitro. To investigate the effects of GDF11 propeptide on GDF11 function in vivo, we generated transgenic mice that over-express the propeptide cDNA in skeletal tissue. The transgenic mice showed formation of extra ribs on the seventh cervical vertebra (C7) as a result of transformation of the C7 vertebra into a thoracic vertebra. The GDF11 propeptide transgene mRNA was detected in tail tissue in embryos and was highly expressed in tail and calvaria bones after birth. A high frequency of C7 rib formation was noticed in the transgenic mouse line with a high level of transgene expression. The anterior boundaries of Hoxa-4 and Hoxa-5 mRNA in situ expressions showed cranial shifts from their normal prevertebra locations in transgenic embryos. These results demonstrated significant effects of GDF11 propeptide transgene on vertebral formation, which are likely occurring through depressing GDF11 function and altered locations of Hoxa-4 and Hoxa-5 expression.

Using color Doppler sonography to identify the perivesical umbilical arteries: a useful method in the prenatal diagnosis of omphalocele-exstrophy-imperforate anus-spinal defects complex.

OBJECTIVE: To describe the different prenatal sonographic findings in 3 cases of omphalocele-exstrophy-imperforate anus-spinal defects (OEIS) complex, or cloacal exstrophy. METHODS: Three patients with OEIS complex were examined by sonography. In 2 (cases 2 and 3) of the 3 cases, color Doppler sonography was applied to the area of cord insertion and the abdominal mass to determine the origin of the abdominal mass. RESULTS: Three cases of OEIS complex with different sonographic appearances are included in this series. An absent bladder without an abdominal mass but with bowel floating in the amniotic cavity was revealed in case 1; an absent bladder with a lower anterior abdominal mass was found in the second trimester in case 2; and a large cystlike mass located in the anterior abdominal wall was found in case 3. Color Doppler imaging showed that the abdominal mass originated from the urinary bladder in cases 2 and 3; therefore, OEIS complex was presumptively diagnosed antenatally in these cases. In all cases, OEIS complex was confirmed postnatally. CONCLUSIONS: Omphalocele-exstrophy-imperforate anus-spinal defects complex should be considered in patients with an absent bladder combined with either an anterior abdominal wall mass or defects. Special attention should be given to search for other combined anomalies. We suggest that color Doppler sonography for identifying the perivesical umbilical arteries is a very useful method in establishing of the diagnosis of OEIS complex.

The embryogenesis of congenital vertebral dislocation: early embryonic buckling?

Congenital vertebral dislocation (CVD) is a rare congenital spinal malformation characterized by a translatory or rotatory vertebral displacement, or both, at a single level, that results in an abrupt angulation of the neural canal. The more caudal vertebra is dysplastic and appears at first glance to be posteriorly dislocated into the vertebral canal as a posterior hemivertebra, but is actually well aligned with the more caudal vertebral column. Unfortunately, the present classification of complex congenital vertebral anomalies is confusing, and CVD has been grouped together with other congenital vertebral malformations under the terms 'segmental spinal dysgenesis', 'medial spinal aplasia', and others. Moreover, a putative embryonic mechanism has never been proposed for CVD. Based upon our experience with 6 children and a critical review of the literature, we identify CVD as a distinct entity having characteristic anatomical features. We propose a novel putative embryonic mechanism - early embryonic 'buckling' - which likely occurs by the 6th embryonic week, prior to the period of axonal outgrowth and the beginning of vertebral chondrification.

Congenital heart disease in spondylothoracic dysostosis: two familial cases.

Two familial cases of spondylothoracic dysostosis are reported. Both cases had severe congenital heart disease in addition to the skeletal malformations which are characteristic of the condition.