Prenatal diagnosis of caudal regression with heterotaxy syndrome: "A mermaid with a broken heart".

Caudal regression syndrome (CRS) is a rare congenital malformation with varying degrees of early gestational developmental failure. It is characterized by agenesis of the sacrum and lumbar spine, with lower limb neurological deficit and accompanying deformities of the pelvis, lower extremities, genitourinary, and gastrointestinal systems. We report a case of CRS associated with rare complex congenital heart defect, that is, heterotaxy syndrome, diagnosed prenatally.

Normal development of sacrococcygeal centrum ossification centers in the fetal spine: a postmortem magnetic resonance imaging study.

PURPOSE: To describe the temporal pattern of the appearance of the S1-Co1 centrum ossification centers (COCs) and provide reference data for the S1-S5 COCs and sacral length at various gestational ages (GAs). METHODS: Postmortem magnetic resonance imaging (MRI) was performed on 71 fetuses (GA, 17-42 weeks) using the 3D dual-echo steady-state with water excitation T2 sequence in the sagittal plane. To confirm the reliability of this sequence, the MRI data were compared with the CT and histologic data obtained from two fetuses (GAs, 21 and 30 weeks). The presence or absence of each sacrococcygeal COC was recorded. Sacral length and S1-S5 COC height, sagittal diameter, transverse diameter, cross-sectional area, and volume were measured. RESULTS: All fetuses showed S1-S3 COCs by 17 weeks, S4 COCs by 19 weeks, and S5 COCs by 28 weeks. The S4, S5, and Co-1 COCs were visualized in 70 (98.59%), 51 (71.83%), and 21 (29.58%) fetuses, respectively. Sacral length, height, sagittal, and transverse diameters increased linearly, while cross-sectional area and volume increased exponentially with advancing GA. Mean growth rates of the sagittal and transverse diameters, cross-sectional area, and volume, but not of height, significantly differed among the S1-S5 vertebrae. CONCLUSION: We have presented the timing of appearance of individual sacrococcygeal COCs and the age-specific, normative MRI reference values for sacral length and the morphometric parameters of the sacral COCs, which are of clinical importance in the diagnosis of congenital sacral abnormalities and skeletal dysplasia.

How to Explore Fetal Sacral Agenesis Without Open Dysraphism: Key Prenatal Imaging and Clinical Implications.

The estimated prevalence of fetal caudal dysgenesis is 1 per 100,000 births. The functional prognosis of sacral agenesis is dominated by the large spectrum of associated caudal malformations. Except for cases associated with hydrocephalus secondary to open spinal dysraphism or chromosomal anomalies, association with mental deficiency is rare. We propose a systematic prenatal approach to cases of fetal sacral agenesis based on 9 etiologic items: clinical context, type of sacral dysgenesis, associated spinal cord malformations, mobility of lower limbs, investigation of the presacral region, analysis of the gastrointestinal tract, analysis of the genitourinary tract, associated vertebral defects, and cytogenetic analysis.

Enigmatic human tails: A review of their history, embryology, classification, and clinical manifestations.

The presence of a human tail is a rare and intriguing phenomenon. While cases have been reported in the literature, confusion remains with respect to the proper classification, definition, and treatment methods. We review the literature concerning this anatomical derailment. We also consider the importance of excluding underlying congenital anomalies in these patients to prevent neurological deficits and other abnormal manifestations.

Fetal development of the mesonephric artery in humans with reference to replacement by the adrenal and renal arteries.

According to the classical ladder theory, the mesonephric arteries (MAs) have a segmental arrangement and persist after regression of the mesonephros, with some of these vessels becoming definitive renal arteries. To avoid interruption of blood flow, such a vascular switching would require an intermediate stage in which two or more segmental MAs are connected to a definitive renal artery. To examine developmental changes, especially changes in the segmental distribution of MAs, we studied serial paraffin sections of 26 human embryos (approximately 5-7 weeks). At 5-6 weeks, 1-2 pairs of MAs ran anterolaterally or laterally within each of the lower thoracic vertebral segments, while 2-5 pairs of MAs were present in each of the lumbar vertebral segments, but they were usually asymmetrical. The initial metanephros, extending along the aorta from the first lumbar to first sacral vertebra, had no arterial supply despite the presence of multiple MAs running immediately anterior to it. Depending on increased sizes of the adrenal and metanephros, the MAs were reduced in number and restricted in levels from the twelfth thoracic to the second lumbar vertebra. The elimination of MAs first became evident at a level of the major, inferior parts of the metanephros. Therefore, a hypothetical arterial ladder was lost before development of glomeruli in the metanephros. At 7 weeks, after complete elimination of MAs, a pair of symmetrical renal arteries appeared near the superior end of the metanephros. In conclusion, the MAs appear not to persist to become a definitive renal artery.

Traffic jam in the primitive streak: the role of defective mesoderm migration in birth defects.

Gastrulation is the process in which the three germ layers are formed that contribute to the formation of all major tissues in the developing embryo. We here review mouse genetic models in which defective gastrulation leads to mesoderm insufficiencies in the embryo. Depending on severity of the abnormalities, the outcomes range from incompatible with embryonic survival to structural birth defects, such as heart defects, spina bifida, or caudal dysgenesis. The combined evidence from the mutant models supports the notion that these congenital anomalies can originate from perturbations of mesoderm specification, epithelial-mesenchymal transition, and mesodermal cell migration. Knowledge about the molecular pathways involved may help to improve strategies for the prevention of major structural birth defects.

Going out on a limb for a difficult diagnosis: a case report.

Sacral tumors with fetiform features are rare and pose a diagnostic challenge to the ultrasonologist. Sacrococcygeal teratomas (SCT) and parasitic twins can have very similar sonographic features but have different implications to an affected pregnancy. While postnatal histopathology is ultimately necessary to distinguish between a SCT and a heteropagus twin, certain characteristics, such as the presence of a vertebral column and the pattern and rate of tumor growth, may be useful to guide counseling and management decisions.

Human fetal anatomy of the coccygeal attachments of the levator ani muscle.

In contrast to the attachments to the pubis and rectum, there is little information on fetal development of the coccygeal attachment of the levator ani muscles. We find that at 9 weeks, the coccygeus muscle is a large muscle facing the piriformis or gluteus maximus and inserting onto the ischial spine, whereas the levator ani is restricted to the area near the pubis. By 12 weeks, the levator ani also obtains attachment to the ischial spine immediately ventral to the coccygeus muscle. The most superior part of the coccygeus muscle occupies a space at an angle between the pelvic splanchnic and pudendal nerves. Notably, medial to the coccygeus muscle, a third parasagittal muscle (previously termed the sacrococcygeus anterior) appears by 12 weeks, increases in mass by 18 weeks, and connects and mixes with the dorsal end of the levator ani by 18-20 weeks. Thus, the coccygeal attachment of the levator ani appears not to depend on the dorsal extension of the muscle itself but on fusion with the sacrococcygeus anterior. Therefore, the final levator sheet is formed medial (internal) to the coccygeus muscle and originates from two distinct anlage.

Sacrococcygeal teratoma over two decades: birth prevalence, prenatal diagnosis and clinical outcomes.

OBJECTIVE: The birth prevalence and malignant tumour recurrence of sacrococcygeal teratoma (SCT) have not been clearly defined. We conducted this study to determine the birth prevalence, prenatal detection rate, frequency of tumour recurrence and outcome of SCT in a population-based cohort. METHODS: Cases were identified from a population-based, regional database of congenital anomalies for the years 1985-2006. Prenatal diagnosis, management details, tumour recurrence and outcome were obtained from case records and cross linked with a regional oncology database. RESULTS: There were 754,172 live births and 28 live born infants with SCT giving a birth prevalence of 1 per 27 000 live births. There was a prenatal diagnosis in 50% of cases. No cases presenting in the neonatal period had malignant tumour present at diagnosis or subsequent tumour recurrence. Nine (37.5%) of the survivors had chronic morbidities. CONCLUSIONS: The birth prevalence of SCT was higher than that of previously reported. Infants who were live born and survived definitive surgical management had a good prognosis.

Terminal myelocystocele and sacrococcygeal teratoma: a comparison of fetal ultrasound presentation and perinatal risk.

This case exemplifies the difficulty in differentiating cystic sacrococcygeal teratoma and terminal myelocystocele. Fetal sonography presentation and perinatal risks of sacrococcygeal teratoma and terminal myelocystocele are compared, and we emphasize the importance of obtaining fetal MR imaging to establish an accurate diagnosis.

[Sacrococcygeal teratoma--a case report and literature review].

Sacrococcygeal teratoma (SCT) is the most frequent solid congenital tumor in the fetus and newborn. We present a case report of prenatally detected SCT with a favorable outcome after vaginal birth complicated by mechanic dystocia.

Sirenomelia sequence according to the distance between the first sacral vertebra and the ilia.

The development of the iliac bones and lower limbs are parallel processes depending on the normal ontogeny of the caudal blastema [O'Rahilly and Müller, 1989; Opitz, 1993; Opitz et al., 2000]. We hypothesized that the pathogenetic mechanisms leading to fused lower limbs would in parallel displace the ilia caudally and medially and that the degree of this displacement might correlate with the severity of the iliac and lower limb defects. Thus the purpose of the study was to test this hypothesis in a sample of 12 sirenomelic fetuses. The fetuses GA 16-39 weeks, spontaneously or therapeutically aborted, were radiographed in the frontal projection as part of a requested autopsy. From each radiograph, a line was drawn connecting the most cranial part or the two ilia. After that the distance was measured vertically between this line and the most cranial part of the first sacral vertebral body (iliac-sacral distance (ISD)). A second distance was measured horizontally between the most lateral part of the two iliae (bi-iliac distance (BD)). As a result, ISD correlates with the iliac/femur phenotype. Separate ilia and femora occur only in cases with normal ISD. Fused ilia or femora or both are seen only in fetuses with mildly increased ISD, whereas a single iliac bone and femur occur only in cases with greatly increased ISD. The increase of the ISD does not correlate with the severity of more distal limb involvement. There was a correlation between the ISD and the BD values; the higher the ISD, the shorter the BD. Based on these findings, we propose an extended classification of Sirenomelia to be tested by other researchers.

Somites, spinal Ganglia, and centra. Enumeration and interrelationships in staged human embryos, and implications for neural tube defects.

Serial sections of 99 human embryos from Carnegie stages 8-23 were investigated and 38 graphic reconstructions were evaluated. At stage 9 somite 1 is of appreciable size and is separated from the otic disc, as also in the next several stages by rhombomeres and pharyngeal arches 3 and 4, thereby differing from the chick. At stage 10 somite 1 begins to differentiate into sclerotome and dermatomyotome. At stage 11 spinal neural crest begins to develop. At stage 12 parts of somites 1-4 are being transformed into the hypoglossal cell cord. It is stressed that the numbers of somites present at stages 9-12 are part of the definition of those stages. At stage 13 dense and loose zones begin to be detectable rostrally in the sclerotomes and also, although out of phase, in the perinotochord. Spinal ganglia begin to develop in phase with the somites. At stages 14-16 the maximum number of somites observed was 38-39 rather than 42-44, as usually given. Moreover, they did not extend to the tapered end of the trunk, which is not a (vertebrated) 'tail'. At stages 17-23 the maximum number of centra was 38-39, including coccygeal vertebrae 4-5. Although most of the somites appear during primary development, all of the spinal ganglia develop during secondary development (stages 13-18). The number of ganglia was at a maximum of 35 at stage 18, but was reduced to 32 already by stage 23. Important points confirmed in this study are that the number of occipital somites in the human is four, and that the level of final closure of the caudal neuropore is future somite 31, which represents approximately future sacral vertebra 2. The interpretation of relevant neural tube defects is discussed in the light of the findings. The ascensus of the conus medullaris during the fetal period is well established, but a concomitant ascent of the situs neuroporicus is proposed here, and has implications for defects that involve tethering of the spinal cord. The main results are integrated in comprehensive graphic representations of the levels and the interrelationships of (a) somites and centra, and (b) somites, neural crest, and spinal ganglia. These may aid in the elucidation of some frequently occurring anomalous conditions.

Newborn with an open posterior hip dislocation and sciatic nerve injury after intrauterine radiofrequency ablation of a sacrococcygeal teratoma.

Advanced prenatal ultrasonography techniques have allowed for better understanding of the natural history, treatment, and prognosis of sacrococcygeal teratomas. Several intrauterine surgical techniques to debulk the tumor when fetal and maternal life are in jeopardy have been described. Orthopaedic impairment, such as lower extremity weakness and swelling, also has been described in association with sacrococcygeal teratomas. The authors report on a newborn in whom a large soft tissue defect overlying the posterior hip region with direct exposure of the disarticulated hip joint existed at the time of birth, which resulted from intrauterine radiofrequency ablation of a sacrococcygeal teratoma. This unexpected complication has resulted in a loss of sciatic nerve function, malformation of the acetabulum and femoral head, and loss of the left ischium, coccyx, inferior sacrum, gluteal, adductor and piriformis muscles, and posterior hip capsule. At 16 months of age, the patient has a flaccid left lower extremity with a hypoplastic hip joint.

Developmental expression of glycine immunoreactivity and its colocalization with GABA in the embryonic chick lumbosacral spinal cord.

The development of immunoreactivity for the putative inhibitory amino acid neurotransmitter glycine was investigated in the embryonic and posthatched chick lumbosacral spinal cord by using postembedding immunocytochemical methods. Glycine immunoreactive perikarya were first observed at embryonic day 8 (E8) both in the dorsal and ventral gray matters. The number of immunostained neurons sharply increased by E10 and was gradually augmented further at later developmental stages. The general pattern of glycine immunoreactivity characteristic of mature animals had been achieved by E12 and was only slightly altered afterward. Most of the immunostained neurons were located in the presumptive deep dorsal horn (laminae IV-VI) and lamina VII, although glycine-immunoreactive neurons were scattered throughout the entire extent of the spinal gray matter. By using some of our previously obtained and published data concerning the development of gamma-aminobutyric acid (GABA)-ergic neurons in the embryonic chick lumbosacral spinal cord, we have compared the numbers, sizes, and distribution of glycine- and GABA-immunoreactive spinal neurons at various developmental stages and found the following marked differences in the developmental characteristics of these two populations of putative inhibitory interneurons. (i) GABA immunoreactivity was expressed very early (E4), whereas immunoreactivity for glycine appeared relatively late (E8) in embryonic development. (ii) In the ventral horn, GABA immunoreactivity declined, whereas immunoreactivity for glycine gradually increased from E8 onward in such a manner that the sum of glycinergic and GABAergic perikarya remained constant during the second half of embryonic development. (iii) Glycinergic and GABAergic neurons showed different distribution patterns in the spinal gray matter throughout the entire course of embryogenesis as well as in the posthatched animal. When investigating the colocalization of glycine and GABA immunoreactivities, perikarya immunostained for both amino acids were revealed at all developmental stages from E8 onward, and the proportions of glycine- and GABA-immunoreactive neurons that were also immunostained for the other amino acid were remarkably constant during development. The characteristic features of the development of the investigated putative inhibitory spinal interneurons are discussed and correlated with previous neuroanatomical and physiological studies.

Presacral tumors: case report, review of the literature.

A case report involving a 42-year-old female is presented. The symptoms and objective physical findings manifest a diagnostic problem. The anatomical site of the tumor depends on the consideration of the numerous possible etiological factors, and one of which is the embryologic knowledge of the region involved. The clinical, pathological, and embryologic features of a case of presacral tumor is presented.

Colonization of the bowel by neural crest-derived cells re-migrating from foregut backtransplanted to vagal or sacral regions of host embryos.

The enteric nervous system (ENS) in avian embryos is formed by cells that migrate to the bowel from vagal and sacral regions of the neural crest. Experiments were carried out to evaluate the developmental potential of crest-derived cells at the time they colonize the gut. Backtransplantation of E4 quail foregut (or control aneuronal hindgut) was used to determine whether crest-derived cells that have previously colonized the bowel are capable of following defined neural crest migration pathways in host embryos. Vagal and sacral, but not truncal, backgrafts provided donor cells for the host's bowel. These cells were immunostained by the neural crest marker, NC-1, restricted to the ENS, and appeared only when foregut was backgrafted; therefore, they were crest-derived. In order for cells to migrate to the host's bowel, backgrafts evidently had to be located in the vicinity of the neuraxis at the time crest-derived cells exited from them. When vagal grafts moved away from the neuraxis, crest-derived donor cells colonized cephalic ganglia and the vagus nerves near the grafts; however, such cells did not migrate down the vagi to the host's gut. Sacral backgrafts provided crest-derived cells for the bowel only if the donor gut was transplanted prior to the formation of somite 28, at the level of the disappearing primitive streak. Cells from vagal backgrafts were capable of reaching the host's cloaca, but backgrafts placed at a sacral level colonized only the post-umbilical bowel. In addition, donor cells proliferated extensively within the host's gut. Whenever the host's gut was colonized, donor crest-derived cells were also found in non-enteric targets including nerves, cephalic (vagal backgrafts), or sympathetic (sacral backgrafts) ganglia; however, donor cells did not form ectomesenchyme or melanocytes. These data suggest that (i) crest-derived cells that have colonized the bowel remain capable of re-migrating and following defined neural crest migration pathways in host embryos; (ii) remigrating cells must enter these pathways at their start; (iii) the gut stimulates the proliferation of enteric crest-derived cells; (iv) vagal crest-derived cells can follow sacral pathways to reach enteric, Remak's, or sympathetic ganglia; and (v) the migration of crest-derived cells within the gut is determined more by the route they follow to reach the bowel than by their level of origin in the neural crest.

Sacrococcygeal dysgenesis association.

In the malformation analysis of 445 patients ascertained only for a sacrococcygeal malformation, a new phenotype, the sacrococcygeal dysgenesis association (SDA), was delineated in 34%. In addition, sirenomelia patients were found in 12%, the VATER association in 27%, and 27% could not be classified. Heterogeneity in the patients with sacrococcygeal malformations was identified by the differences found in their associated malformations. SDA patients have a relatively small average number (3.3) of anomalies per patient as compared with 9.3 in sirenomelia and 6.2 in VATER patients. SDA abnormalities occurred to a significant degree only in 6 of 20 designated malformation categories (vertebral, rib, pelvic, lower limb, central nervous system [CNS], renal) in contrast to 17 in VATER and 18 in sirenomelia patients. The SDA vertebral malformation pattern also differed from that of VATER/sirenomelia patients as did the high sacrococcygeal agenesis:dysgenesis ratio and low thoracolumbar vertebrae and/or rib hypersegmentations. Most significantly, SDA patients had a large number of CNS anomalies and CNS-related dysfunctions of the urinary and distal intestinal tracts but no anatomic urinary or intestinal tract malformations. This contrasted sharply with the markedly increased occurrences of anatomic abnormalities in these body regions of the sirenomelia and VATER patients. Demographic data such as patient survival, twinning and, particularly, the high (28%) incidence of maternal diabetes in the SDA further support its differentiation from VATER/sirenomelia patients.

The human tail and spinal dysraphism.

Recent publications have endeavoured to differentiate between the true, or vestigial tail, and the pseudotail by clinical and pathological examination, and have indicated the benign nature of the true tail. The true tail arises from the most distal remnant of the embryonic tail, contains adipose, connective, muscle, and nerve tissue, and is covered by skin. Pseudotails represent a variety of lesions having in common a lumbosacral protrusion and a superficial resemblance to vestigial tails. A review of the case reports indicates spina bifida to be the most frequent coexisting anomaly with both. A review of occult spinal dysraphism shows it to be associated with cutaneous signs in more than 50% of instances. Three cases of spinal dysraphism with tail-like cutaneous structures are described and their radiological, operative, and pathological findings presented. The classification of each of the appendages into true tail or pseudotail remains obscure. Although the finding of these three tails was the subject of much curiosity, surgical treatment was clearly designed to adequately deal with the associated dysraphic state. The presence of a tail-like appendage in the lumbosacral region should alert the clinician to the possibility of underlying spinal dysraphism. Preoperative assessment must include a complete neurological history and examination as well as computed tomographic or magnetic resonance imaging.