Evaluation of fibular muscles and prevalence of accessory fibular muscles on fetal cadavers.

PURPOSE: The purpose of this study was to determine clinical importance and morphology of the fibularis longus, brevis, tertius muscles (presented as fibular muscles in this study), and prevalence of accessory fibular muscles (AFM) on fetal cadavers. MATERIALS AND METHODS: In this study, 200 limbs from 100 embalmed fetuses (54 male and 46 female) were studied. Morphology of fibular muscles and the presence of AFM were observed through dissection on fetal legs bilaterally. The absence of fibularis tertius muscle (FT) and the presence of AFM were identified. Length and length of the tendon of AFM were measured. Insertion of AFM was also identified. RESULTS: Mean values and standard deviations of all parameters according to trimesters were calculated. All parameters were increased with age during the fetal period. We determined the absence of FT; no FT was observed in 40 legs of 200 extremities (20%). The AFM was present in 7 of 200 specimens (3.5%). AFM muscles were classified into two types according to their site of origin. CONCLUSION: The present study has revealed the morphology of the fibular muscles and prevalence of the presence of AFM on fetal cadavers. In addition, it has revealed the morphometric development and prevalence of the absence of FT in a large series, and their clinical importance was discussed.

Can Fetal Limb Soft Tissue Measurements in the Third Trimester Predict Neonatal Adiposity?

OBJECTIVES: Neonatal adiposity is associated with chronic metabolic sequelae such as diabetes and obesity. Identifying fetuses at risk for excess neonatal body fat may lead to research aimed at limiting nutritional excess in the prenatal period. We sought to determine whether fetal arm and leg soft tissue measurements at 28 weeks' gestation were predictive of neonatal percent body fat METHODS : In this prospective observational cohort study of singleton term pregnancies, we performed sonography at 28 and 36 weeks' gestation, including soft tissue measurements of the fetal arm and thigh (fractional limb volume and cross-sectional area). We estimated the neonatal body composition (percent body fat) using anthropometric measurements and air displacement plethysmography. We estimated Spearman correlations between sonographic findings and percent body fat and performed modeling to predict neonatal percent body fat using maternal characteristics and sonographic findings. RESULTS: Our analysis of 44 women yielded a mean maternal age of 30 years, body mass index of 26 kg/m(2), and birth weight of 3382 g. Mean neonatal percent body fat was 8.1% by skin folds at birth and 12.2% by air displacement plethysmography 2 weeks after birth. Fractional thigh volume measurements at 28 weeks yielded the most accurate model for predicting neonatal percent body fat (R(2) = 0.697; P = .001), outperforming models that used abdominal circumference (R(2)= 0.516) and estimated fetal weight (R(2)= 0.489). CONCLUSIONS: Soft tissue measurements of the fetal thigh at 28 weeks correlated better with neonatal percent body fat than currently used sonographic measurements. After validation in a larger cohort, our models may be useful for prenatal intervention strategies aimed at the prevention of excess fetal fat accretion and, potentially, optimization of long-term metabolic health.

The long arms of anencephaly: A refutation.

A paper published in 1925 reported that human fetuses with anencephaly have arms that are longer than normal. This finding was accepted as true through the early 1990s. An analysis of body dimensions done in 1996 and enlarged and updated here shows that the arms of human fetuses with anencephaly are appropriate for gestational age and normal in proportion to their leg lengths. A subtle difference in measurement technique was found to explain the discordant findings.

Fetal leg posture in uncomplicated breech and cephalic pregnancies.

BACKGROUND: The objective of our study was to determine differences in prenatal leg posture development between breech and cephalic-born babies. MATERIALS AND METHODS: Ten healthy fetuses in breech and ten healthy fetuses in cephalic presentation were observed by means of weekly ultrasounds from 33 weeks gestational age until birth to assess leg posture. RESULTS: The breech fetuses showed a clear preference for an extended leg position; they spent significantly more time with their knees in extension than the cephalic fetuses (p<0.001). The cephalic fetuses showed significantly more leg-crossing than the breech fetuses (p<0.01). For both findings, no significant change over time could be observed in either group. CONCLUSION: These findings show that the intra-uterine position does influence the fetal postural and motor development. However, it seems unlikely that intra-uterine movement restriction can solely be held accountable for the observed differences in leg position between breech and cephalic fetuses.

Sonographic nomogram of the fetal calf between 15 and 42 weeks' gestation using 3-dimensional sonography.

OBJECTIVE: The purpose of this study was to establish a new reference growth chart of calf muscle biometric measurements throughout gestation in normal singleton pregnancies. METHODS: A prospective cohort study was designed. One hundred pregnant women were included in the study and assessed by 3-dimensional sonography. Excluded were those with multiple pregnancies, congenital anomalies, abnormal karyotypes, and polyhydramnios or oligohydramnios. Three-dimensional multiplanar sonographic images were used to measure the calf muscles: soleus, gastrocnemius, popliteal, peroneus longus, and tibialis posterior. RESULTS: Calf muscle widths increased with increasing gestational age (R(2) = 0.857; P < .0001), and the ratio between calf muscles and the tibia increased as well (R(2) = 0.356; P = .001). CONCLUSIONS: The data provide a nomogram of calf width with a direct correlation between muscle growth and gestational age. This nomogram can offer a basis for normal calf development and may assist in distinguishing between different etiologies leading to clubfoot and other joint contractures associated with calf atrophy.

Prenatal diagnosis of Dandy-Walker malformation associated with distal limb deficiencies.

We report the perinatal findings of a 23 gestational-week fetus with Dandy-Walker malformation (DWM), ventriculomegaly, symmetrical transverse limb deficiencies, hypertelorism, frontal bossing, low-set ears, and a depressed nasal bridge. The karyotype was 46,XX. We believe that this combination is significant. Concomitant DWM and symmetrical distal limb deficiencies may represent a new entity that awaits more new cases for further delineation.

Endoscopic release of limb constriction rings in utero.

Amniotic band syndrome is a sporadic condition that may result in constriction bands, amputation and multiple craniofacial, visceral and body wall defects. It occurs in 1/1,200 to 1/15,000 live births. Most cases present with multiple congenital anomalies that are incompatible with life. A small group of fetuses shows isolated limb constrictions that may cause severe limb dysfunction or limb amputation if left untreated. Successful in utero surgical lyses of constriction rings have been reported. We report a case of constriction amniotic bands involving both legs and compromising blood flow to the distal extremity. The constriction ring was successfully released by a minimally invasive endoscopic surgical technique avoiding severe limb dysfunction or foot amputation.

Cartilage oligomeric matrix protein is involved in human limb development and in the pathogenesis of osteoarthritis.

As a member of the thrombospondin gene family, cartilage oligomeric protein (COMP) is found mainly in the extracellular matrix often associated with cartilage tissue. COMP exhibits a wide binding repertoire and has been shown to be involved in the regulation of chondrogenesis in vitro. Not much is known about the role of COMP in human cartilage tissue in vivo. With the help of immunohistochemistry, Western blot, in situ hybridization, and real-time reverse transcription-polymerase chain reaction, we aimed to elucidate the role of COMP in human embryonic, adult healthy, and osteoarthritis (OA) cartilage tissue. COMP is present during the earliest stages of human limb maturation and is later found in regions where the joints develop. In healthy and diseased cartilage tissue, COMP is secreted by the chondrocytes and is often associated with the collagen fibers. In late stages of OA, five times the COMP mRNA is produced by chondrocytes found in an area adjacent to the main defect than in an area with macroscopically normal appearance. The results indicate that COMP might be involved in human limb development, is upregulated in OA, and due to its wide binding repertoire, could play a role in the pathogenesis of OA as a factor secreted by chondrocytes to ameliorate the matrix breakdown.

Human syndromes with congenital patellar anomalies and the underlying gene defects.

Genetic disorders characterized by congenital patellar aplasia or hypoplasia belong to a clinically diverse and genetically heterogeneous group of lower limb malformations. Patella development involves different molecular and cellular mechanisms regulating dorso-ventral patterning, cartilage and bone formation along endochondral ossification pathways, and growth. Several human genes that are important for patella development have been uncovered by the study of human limb malformation syndromes, yet causative genes for many more such disorders await to be identified and their complex interactions in the developmental pathways deciphered. Mutant animal models of congenital patellar aplasia or hypoplasia are certainly instrumental to create more insight into this aspect of limb development. Moreover, investigation of the complete phenotype of human syndromes and animal models may reveal novel insights into the pleiotropic roles of the responsible genes in the normal developmental of other organ systems. In this review, the phenotype and gene defects of syndromes with congenital patellar aplasia or hypoplasia will be discussed, including the nail patella syndrome, small patella syndrome, isolated patella aplasia hypoplasia, Meier-Gorlin syndrome, RAPADILINO syndrome, and genitopatellar syndrome.

Anomalies of the forebrain with radial limb defects: Garcia-Lurie-Steinfeld syndrome?

BACKGROUND: Severe anomalies of the forebrain together with radial limb anomalies have been reported in Steinfeld syndrome, XK aprosencephaly, and partial monosomy 13q. Steinfeld syndrome is an extremely variable autosomal dominant condition that, in severe cases, is characterized by holoprosencephaly, radial limb defects, and renal and/or cardiac defects. In mild cases there may be only thumb hypoplasia, ocular coloboma, or oral clefts. XK aprosencephaly, also called Garcia-Lurie syndrome (GLS), is a usually sporadic disorder with radial limb defects and aprosencephaly/atelencephaly. Based on two atypical sibships, autosomal recessive inheritance has been suggested. Two patients with variations of monosomy 13q have been described with atelencephaly but, generally, Steinfeld and XK aprosencephaly patients are chromosomally normal. Holoprosencephaly in 13q deletion patients appears to be due to ZIC2 mutations, but ZIC2 has not been previously tested in Steinfeld syndrome or GLS patients. CASES: We report three sporadic cases with clinical features intermediate between Steinfeld and GLS, including severe forebrain malformations and radial limb defects. All had normal karyotypes, and mutations in ZIC2 were absent in the two cases tested. CONCLUSIONS: In our cases and in the literature there is significant clinical overlap between Steinfeld syndrome and GLS. We propose these conditions may not be nosologically or etiologically distinct. The spectrum of severe forebrain anomalies in these conditions is broader than previously thought and may include some neural tube defects. Mild cases are difficult to identify and the full range of expression remains unknown. Autosomal dominant inheritance with incomplete penetrance and frequent new mutations is postulated. Thorough clinical evaluation is recommended for children with severe forebrain and radial limb defects.

Perforating veins of the shin in human foetuses.

There are 3 groups of perforating veins of the shin: the medial, the lateral and the internal sural perforating veins. Dysfunction of these veins is one of the main factors in venous hypertension. There is a lack of data in the literature concerning perforating veins of the shin in human foetuses. The aim of this study was identification of the perforating veins of the shin in human prenatal development. The material examined included 88 human lower limbs of foetuses (21 males and 23 females) aged from 16 to 38 weeks of intra-uterine life. The perforating veins were dissected under a steromicroscope. The number of perforating veins was analysed in relation to the sex of the foetus and the side of a body. In our study perforating veins of the shin did not show sexual or syntopic dimorphism. Between 2 and 6 Cockett's perforating veins were constantly present. Of these veins 80% divided into ascending and descending branches. Fibular perforating veins were found more often (90.9%) than Boyd's perforating veins (21.6%). Between 1 and 3 fibular perforating veins were observed but in 9% of cases they were entirely absent.

Multiple arterial thrombi and in utero leg gangrene in an infant of a diabetic mother.

This case report is of an infant of a diabetic mother who presented with lower extremity gangrene occurring in utero that necessitated a below the knee amputation at 3 hours of age. The association of venous thrombi in infants of diabetic mothers (IDMs) has been firmly established. However, in this case the thrombi were arterial and resulted in gangrene during the second trimester of gestation. The reason for the increased tendency to develop thrombi in infant of diabetic mothers has not been elucidated. We did an extensive workup of this infant to look for a cause of the arterial thrombus. The only abnormality found was in the plasminogen activity, which was significantly lower than the reference values for infants of the same gestational and chronological age. The significance of this finding on the propensity of IDMs to develop thrombi is discussed.

Prenatal diagnosis of arthrogryposis multiplex congenita with increased nuchal translucency but without any underlying fetal neurogenic or myogenic pathology.

Arthrogryposis multiplex congenita is a general term for congenital multiple joint contractures, the aetiology of which is variable. Prenatal diagnosis is usually based on the detection of diminished fetal movements and joint contractures on ultrasound. There are also reports of early diagnosis of arthrogryposis in the first and early second trimester by detection of subcutaneous oedema. We report another case of arthrogryposis multiplex congenita with increased nuchal translucency and scoliosis diagnosed by ultrasonography at 15 weeks of gestation. The pregnancy was terminated at the request of the parents. Post-mortem examination revealed that it was not associated with fetal myopathy or neuropathy. Multiple joint contractures with increased nuchal translucency without any underlying fetal neurogenic and myogenic pathology may be a distinct form of arthrogryposis multiplex congenita.

[Aneurysm of a persistent sciatic artery: five case reports]. / Anévrisme sur artère sciatique persistante.

We report five cases of a persistent sciatic artery. The lesion was unilateral in all cases. Four patients were treated by exclusion of the aneurysm with ligature of the internal iliac artery with an associated femoropopliteal bypass in two. Surgical treatment was declined by one patient. We discuss the embryology, pathology, clinical aspects and surgical procedures involved.

Bart syndrome: the congenital localized absence of skin may follow the lines of Blaschko. Report of six cases.

Three cutaneous manifestations are characteristic of Bart syndrome: congenital localized absence of skin (CLAS), mucocutaneous blistering, and nail abnormalities. Six cases of Bart syndrome are herein reported. Localized absence of skin is present at birth, particularly on the anterior aspects of the lower extremities and dorsa of the feet. Physical trauma in utero has been proposed as a mechanism to explain the denuded areas on the limbs. The recurrent, highly similar pattern of the congenital defect in regard to location and clinical appearance in our patients and in most of the reported cases strongly suggests that trauma is too simplistic an explanation. Because of the observed bilateral and symmetric distribution of denuded areas in an S-shaped broad band, their sharply demarcated borders, the involvement of the toe webs, and the frequent similar involvement of the soles, we suggest that congenital localized absence of skin in Bart syndrome may follow the lines of Blaschko.

Mouse homolog of the Drosophila Pc-G gene esc exerts a dominant negative effect in Drosophila.

The Polycomb group genes are involved in maintaining long term transcriptional repression of the homeotic genes in both Drosophila and mammals. The mouse eed locus encodes the highly conserved ortholog of the Drosophila ESC protein. To test the functional conservation between the two genes, eed was introduced into the fly to determine whether it could rescue the esc mutant phenotype. eed exerted a dominant negative effect on the leg transformation phenotype associated with the esc mutation. This result is interpreted in light of in vitro protein-protein binding data and in vivo polytene chromosome staining indicating the lack of significant interaction between Eed and fly E(Z), a molecular partner of ESC. genesis 26:67-76, 2000