Spondylothoracic dysplasia in two siblings

The spondylothoracic dysplasia syndrome is characterized by congenital malformations of vertebrae and ribs. As a consequence of the anomalous development of the vertebral column, the neck and thorax are short, and the normal head looks as if emerging from the shoulders. The thorax is short and asymmetric with an increased anteroposterior diameter. Dorsolumbar lordosis and a protuberant abdomen are present. The extremities though normal in length appear long relative to the shortened trunk. Short stature results from the vertebral abnormalities. The syndrome was seen in 2 siblings of nonconsanguineous parents.

SED-brachydactyly and distinctive speech: Report of a new familial case

Background: Spondyloepiphyseal dysplasia-brachydactyly and distinctive speech (SED-BDS) is a syndrome characterized by short stature, disproportionately short limbs, peculiar face, thick and abundant hair, high-pitched and coarse voice, small epiphyses, brachymetacarpalia, brachymetatarsalia and brachy-phalangia of fingers and toes, small pelvis and delayed carpal bone age, among other features. Case Report: We report a Brazilian patient with father, brother and sister presenting with the same typical features of the syndrome. Clinically, he showed disproportionately short stature, rhizo-meso-acromelic shortness of the extremities, short hands and feet, a peculiar distinctive high-pitched voice, peculiar facies, and other features already reported as characteristic of this syndrome. Radiographic fndings included shape anomalies of the vertebral bodies such as cuboid-shaped vertebral bodies, mild scoliosis, short and broad tubular bones, brachymetacarpalia, brachymetatarsalia, and brachy-dactyly, lumbar hyperlordosis, generalized osteopenia, and hypoplastic iliac wings. Conclusions: Few cases have been described, as this is a rare skeletal dysplasia. This paper describes a new familial case of SED-BDS. © The American Journal of Case Reports.

Development of a multi-scale finite element model of the osteoporotic lumbar vertebral body for the investigation of apparent level vertebra mechanics and micro-level trabecular mechanics.

Osteoporotic spinal fractures are a major concern in ageing Western societies. This study develops a multi-scale finite element (FE) model of the osteoporotic lumbar vertebral body to study the mechanics of vertebral compression fracture at both the apparent (whole vertebral body) and micro-structural (internal trabecular bone core)levels. Model predictions were verified against experimental data, and found to provide a reasonably good representation of the mechanics of the osteoporotic vertebral body. This novel modelling methodology will allow detailed investigation of how trabecular bone loss in osteoporosis affects vertebral stiffness and strength in the lumbar spine.

Investigating the change in three dimensional deformity for idiopathic scoliosis using axially loaded MRI

Background: Adolescent idiopathic scoliosis is a complex three-dimensional deformity, involving a lateral deformity in the coronal plane and axial rotation of the vertebrae in the transverse plane. Gravitational loading plays an important biomechanical role in governing the coronal deformity, however, less is known about how they influence the axial deformity. This study investigates the change in three-dimensional deformity of a series of scoliosis patients due to compressive axial loading. Methods: Magnetic resonance imaging scans were obtained and coronal deformity (measured using the coronal Cobb angle) and axial rotations measured for a group of 18 scoliosis patients (Mean major Cobb angle was 43.4 o). Each patient was scanned in an unloaded and loaded condition while compressive loads equivalent to 50% body mass were applied using a custom developed compressive device. Findings: The mean increase in major Cobb angle due to compressive loading was 7.4 o (SD 3.5 o). The most axially rotated vertebra was observed at the apex of the structural curve and the largest average intravertebral rotations were observed toward the limits of the coronal deformity. A level-wise comparison showed no significant difference between the average loaded and unloaded vertebral axial rotations (intra-observer error = 2.56 o) or intravertebral rotations at each spinal level. Interpretation: This study suggests that the biomechanical effects of axial loading primarily influence the coronal deformity, with no significant change in vertebral axial rotation or intravertebral rotation observed between the unloaded and loaded condition. However, the magnitude of changes in vertebral rotation with compressive loading may have been too small to detect given the resolution of the current technique.

Isolation of human lymphatic malformation endothelial cells, their in vitro characterization and in vivo survival in a mouse xenograft model

Human lymphatic vascular malformations (LMs), also known as cystic hygromas or lymphangioma, consist of multiple lymphatic endothelial cell-lined lymph-containing cysts. No animal model of this disease exists. To develop a mouse xenograft model of human LM, CD34NegCD31Pos LM lymphatic endothelial cells (LM-LEC) were isolated from surgical specimens and compared to foreskin CD34NegCD31Pos lymphatic endothelial cells (LECs). Cells were implanted into a mouse tissue engineering model for 1, 2 and 4 weeks. In vitro LM-LECs showed increased proliferation and survival under starvation conditions (P < 0.0005 at 48 h, two-way ANOVA), increased migration (P < 0.001, two-way ANOVA) and formed fewer (P = 0.029, independent samples t test), shorter tubes (P = 0.029, independent samples t test) than foreskin LECs. In vivo LM-LECs implanted into a Matrigel™-containing mouse chamber model assembled to develop vessels with dilated cystic lumens lined with flat endothelium, morphology similar to that of clinical LMs. Human foreskin LECs failed to survive implantation. In LM-LEC implanted chambers the percent volume of podoplaninPos vessels was 1.18 ± 2.24 % at 1 week, 6.34 ± 2.68 % at 2 weeks and increasing to 7.67 ± 3.60 % at 4 weeks. In conclusion, the significantly increased proliferation, migration, resistance to apoptosis and decreased tubulogenesis of LM-LECs observed in vitro is likely to account for their survival and assembly into stable LM-like structures when implanted into a mouse vascularised chamber model. This in vivo xenograft model will provide the basis of future studies of LM biology and testing of potential pharmacological interventions for patients with lymphatic malformations.

Synthesis of GaN nanorods with vertebra-like morphology

GaN nanorods with vertebra-like morphology were synthesized by nitriding Ga2O3/ZnO films at 1000 degrees C for 20min. Ga2O3 thin films and ZnO middle layers were pre-deposited in turn on Si(111) substrates by r.f. magnetron sputtering system. In the flowing ammonia ambient, ZnO was reducted to Zn and Zu sublimated at 1000 degrees C. Ga2O3 was reducted to Ga2O and Ga2O reacted with NH3 to synthesize GaN nanorods in the help of the sublimation of Zn. The structure and morphology of the nanorods were studied by X-ray diffraction (XRD) and scanning electron microscopy (SEM), The composition of GaN nanorods was studied by energy dispersive spectroscopy (EDS) and fourier transform infrared (FTIR) system.

Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register

Objective: To assess the relative risk of major congenital malformation (MCM) from in utero exposure to antiepileptic drug (AEDs).

Malformation Chiari-Like : l’investigation d’une maladie complexe par l’utilisation d’un modèle canin

La malformation de Chiari type 1 (MCI) est une anomalie congénitale de la jonction cranio-cérébrale fréquente avec une incidence de 1:1280. MCI est caractérisée par la descente des amygdales cérébelleuses à travers le foramen magnum et est souvent associée à la syringomyélie. Les causes de cette maladie semblent être multifactorielles incluant des facteurs génétiques. La MCI est similaire à une malformation fréquente chez la race des Griffon Bruxellois (GB) connue sous le nom de Malformation Chiari-like (MCL). Le modèle canin offre l’avantage d’une forte homogénéité génétique réduisant ainsi la complexité de la maladie et facilitant l’identification d’un locus causatif. Une étude d’association du génome entier sur une cohorte de 56 GB suivie d’une cartographie fine sur une cohorte de 217 GB a identifié un locus fortement associé à la MCL sur le chromosome 2 (22 SNPs, valeur P= 7 x 10-8) avec un haplotype de 1.9 Mb plus fréquent chez les non affectés. Une seconde étude d’association du génome entier sur une cohorte de 113 GB a permis d’identifier un 2 ème locus fortement associé à la MCL sur le chromosome 13 (25 SNPs , valeur P= 3 x 10 -7) avec un haplotype de 4 Mb surreprésenté chez les non affectés. Ces régions candidates constituent la première étape vers l’identification de gènes causatifs pour la MCL. Notre étude offre un point d’entrée vers une meilleure compréhension des mécanismes moléculaires sous-tendant la pathogénèse de la MCI humaine.

A novel locus for split-hand/foot malformation associated with tibial hemimelia (SHFLD syndrome) maps to chromosome region 17p13.1-17p13.3

Split-hand/foot malformation (SHFM) associated with aplasia of long bones, SHFLD syndrome or Tibial hemimelia-ectrodactyly syndrome is a rare condition with autosomal dominant inheritance, reduced penetrance and an incidence estimated to be about 1 in 1,000,000 liveborns. To date, three chromosomal regions have been reported as strong candidates for harboring SHFLD syndrome genes: 1q42.2-q43, 6q14.1 and 2q14.2. We characterized the phenotype of nine affected individuals from a large family with the aim of mapping the causative gene. Among the nine affected patients, four had only SHFM of the hands and no tibial defects, three had both defects and two had only unilateral tibial hemimelia. In keeping with previous publications of this and other families, there was clear evidence of both variable expression and incomplete penetrance, the latter bearing hallmarks of anticipation. Segregation analysis and multipoint Lod scores calculations (maximum Lod score of 5.03 using the LINKMAP software) using all potentially informative family members, both affected and unaffected, identified the chromosomal region 17p13.1-17p13.3 as the best and only candidate for harboring a novel mutated gene responsible for the syndrome in this family. The candidate gene CRK located within this region was sequenced but no pathogenic mutation was detected.

Significance of extruded nuclear chromatin (regional nuclear shape malformation) in human spermatozoa: implications for ICSI

The aim of this study was to determine the extent of DNA fragmentation and the presence of denatured single-strand or normal double-strand DNA in spermatozoa with extruded nuclear chromatin (ENC) selected by high magnification. Fresh semen samples from 55 patients were prepared by discontinuous isolate concentration gradient. Spermatozoa with normal nucleus (NN) and ENC were selected at 8400x magnification and placed on different slides. DNA fragmentation was determined by TUNEL assay. Denatured and double-stranded DNA was identified by the acridine orange fluorescence method. DNA fragmentation was not significantly different (p = 0.86) between spermatozoa with ENC (19.6%) and those with NN (20%). However, the percentage of spermatozoa with detectable denatured-stranded DNA in the ENC spermatozoon group (59.1%) was significantly higher (p < 0.0001) than in the NN group (44.9%). The high level of denatured DNA in spermatozoa with ENC suggests premature decondensation and disaggregation of sperm chromatin fibres. The results show an association between ENC and DNA damage in spermatozoa, and support the routine morphological selection and injection of motile spermatozoa at high-magnification intracytoplasmic sperm injection.