Minor sternum and vertebral column congenital defects in Lisbon Identified Skeletal Collection.

This study has mainly a descriptive aim, in which crude prevalence of minor skeletal congenital defects is calculated and sex differences are tested. Prevalence is compared with other studies to recognize regional patterns. Association with age-at-death and year-of-birth is tested to identify impact of environmental stress on minor congenital defects presence. Testing association between defects will identify defects with a probable identical etiology. Chi-square was used to identify sex differences, between studies differences, and to test relationships between defects and Spearman correlation to verify correlation intensity. T-test was used to test age-at-death and year-of-birth differences in defects prevalence. There were no statistically significant differences in prevalence of minor skeletal defects for sex and age-at-death. There were statistically significant differences in year-of-birth for sternal aperture and pectus excavatum (crude prevalence was higher for those who were born earlier). There was a statistical significant association between pectus excavatum and manubrium mesosternal joint and atlas posterior/lateral bridging and notochord defects. For most defects, this study has lower prevalence than other studies. From 18 minor axial skeletal congenital defects analyzed, prevalence ranges from absent to 26.3 (notochord defects). Pectus excavatum and manubrium mesosternal joint might have a similar etiology as well as atlas posterior/lateral bridging and notochord defects. This study has lower prevalence, for almost all defects, than other studies. None of the minor congenital defects tested might, at this time, be considered useful stress markers.

Utility of follow-up standard sonography for fetal anomaly detection.

BACKGROUND: In 2014, the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Imaging Workshop consensus recommended that sonograms be offered routinely to all pregnant women. In the absence of another indication, this examination is recommended at 18-22 weeks of gestation. Studies of anomaly detection often focus on pregnancies at risk for anomalies and on the yield of detailed sonography, topics less applicable to counseling low-risk pregnancies about the benefits and limitations of standard sonography. The clinical utility of follow-up sonogram in low-risk pregnancies for the purpose of fetal anomaly detection has not been established. OBJECTIVE: The objective of the study was to evaluate the utility of follow-up standard sonography for anomaly detection among low-risk pregnancies in a nonreferred population. STUDY DESIGN: We performed a retrospective cohort study of singleton pregnancies that underwent standard sonography at 18-21 6/7 weeks of gestation from October 2011 through March 2018 with subsequent delivery of a live-born infant at our hospital. Pregnancies with indications for detailed sonography in our system were excluded to evaluate fetal anomalies first identified with standard sonography. Anomalies were categorized according to the European Registration of Congenital Anomalies and Twins (EUROCAT) system, with confirmation based on neonatal evaluation. Among those with no anomaly detected initially, we evaluated the rate of subsequent detection according to number of follow-up sonograms, gestational age at sonography, organ system(s) affected, and anomaly severity. Statistical analyses were performed using χ2 and a Mantel-Haenszel test. RESULTS: Standard sonography was performed in 40,335 pregnancies at 18-21 6/7 weeks, and 11,770 (29%) had at least 1 follow-up sonogram, with a second follow-up sonogram in 3520 (9%). Major abnormalities were confirmed in 387 infants (1%), with 248 (64%) detected initially and 28 (7%) and 5 (1%) detected on the first and second follow-up sonograms. Detection of residual anomalies on follow-up sonograms was significantly lower than detection on the initial standard examination: 64% on initial examination, 45% for first follow-up, and 45% for second follow-up (P < .01). A larger number of follow-up examinations were required per anomalous fetus detected: 163 examinations per anomalous fetus detected initially, 420 per fetus detected at the first follow-up examination, and 705 per fetus detected at the second follow-up sonogram (P < .01). The number of follow-up examinations to detect each additional anomalous fetus was not affected by gestational age (P = .7). Survival to hospital discharge was significantly lower for fetuses with anomalies detected on initial (88%) than for fetuses with anomalies undetected until delivery (90 of 91, 99%; P < .002). CONCLUSION: In a low-risk, nonreferred cohort with fetal anomaly prevalence of 1%, follow-up sonography resulted in detection of 45% of fetal anomalies that had not been identified during the initial standard sonogram. Significantly more follow-up sonograms were required to detect each additional anomalous fetus.

One-stage posterior excision of lumbosacral hemivertebrae: Retrospective study of case series and literature review.

Lumbosacral hemivertebrae causes unique problems as early trunk decompensation and long compensatory curve above. There are only a few reports on it. This case series is a fair supplement in the literatures.To evaluate the clinical and radiological outcomes of lumbosacral hemivertebrae resection through 1-stage posterior approach.Between 2005 and 2014, a consecutive series of congenital scoliosis due to lumbosacral hemivertebrae underwent hemivertebrae excision through 1-stage posterior only approach. Demographic, operative, radiological, and quality of life data were reviewed.The mean lumbosacral curve was 29 ±â€Š7° preoperatively, 10 ±â€Š3° postoperatively, and 13 ±â€Š5° at the final follow up. The final correction rate was 55 ±â€Š9%. The gravity trunk shift was 11 ±â€Š3 mm preoperatively, 37 ±â€Š12 mm (range, 6-49 mm) postoperatively, 14 ±â€Š9 mm at final follow up. The rib cage shift was 36 ±â€Š12 mm preoperatively, 19 ±â€Š5 mm postoperatively, and 15 ±â€Š4 mm at the final follow up. The mean blood loss was 527 ±â€Š125 mL and the mean surgery time was 336 ±â€Š98 minutes. The mean follow up period was 41 ±â€Š6 months. Two patients underwent transient neurological complications, 2 had wound bad healing, and 1 got wound infection. No pseudoarthrosis and instrumentation failure was observed.One-stage posterior hemivertebrae excision could gain reasonable outcome. It is crucial to completely resect the hemivertebrae and the Y-shaped disc. Bending the rod to appropriate lordosis is helpful to close the convex side. Early surgical intervene is a preferred choice to restore the trunk balance and avoid extensive fusion. The neurological complication rate is high. Convex radiculopathy is often caused by retraction, it could recover at follow up.

Vascular endothelial growth factor control mechanisms in skeletal growth and repair.

Vascular endothelial growth factor A (VEGF) is a critical regulator of vascular development and postnatal angiogenesis and homeostasis, and it is essential for bone development and repair. Blood vessels serve both as structural templates for bone formation and they provide essential cells, growth factors and minerals needed for synthesis and mineralization, as well as turnover, of the extracellular matrix in bone. Through its regulation of angiogenesis, VEGF contributes to coupling of osteogenesis to angiogenesis, and it directly controls the differentiation and function of osteoblasts and osteoclasts. In this review, we summarize the properties of VEGF and its receptors that are relevant to bone formation and repair; the roles of VEGF during development of endochondral and membranous bones; and the contributions of VEGF to bone healing during different phases of bone repair. Finally, we discuss contributions of altered VEGF function in inherited disorders with bone defects as part of their phenotypes, and we speculate on what will be required before therapeutic strategies based on VEGF modulation can be developed for clinical use to treat patients with bone growth disorders and/or compromised bone repair. Developmental Dynamics 246:227-234, 2017. © 2016 Wiley Periodicals, Inc.

Skeletal Dysplasias That Cause Thoracic Insufficiency in Neonates: Illustrative Case Reports.

Skeletal dysplasias are a heterogeneous group of conditions associated with various abnormalities of the skeleton. Some of them are perinatally lethal and can be diagnosed at birth. Lethality is usually due to thoracic underdevelopment and lung hypoplasia. A correct diagnosis and typing of the skeletal disorder is essential for the prognosis as is genetic counseling of the family. A retrospective review of 12 cases of clinico-radiologic diagnosis of skeletal dysplasia, leading to thoracic insufficiency, was conducted.We aimed to make differential diagnosis with special emphasis on radiological findings, and to emphasize the importance of parental counseling.

Síndrome de GAPO. Un nuevo caso con trombopatía funcional y síndrome de apnea-hipopnea del sueño / GAPO syndrome. A new case with functional thrombopathy and sleep apnea-hypopnea syndrome

Se presenta un nuevo caso de Síndrome de GAPO con otros antecedentes personales no descritos hasta ahora, su motivo de ingreso y evolución. El Síndrome de GAPO es una entidad prácticamente desconocida con sólo 35 casos en el mundo. Gracias a los casos comentados por los distintos autores está aumentando el conocimiento sobre posibles asociaciones con otras entidades o enfermedades, lo que apoya el estudio completo ante cada nuevo diagnóstico de Síndrome de GAPO

We report one case of GAPO syndrome with other personal history not described so far, its reason for admission and evolution. GAPO syndrome is an unknown entity with only 35 cases worldwide. Thanks to the cases discussed by other authors is increasing awareness of potential partnerships with other entities or diseases, supporting the full study on each new diagnosis of GAPO síndrome

Overexpression of Indian hedgehog partially rescues short stature homeobox 2-overexpression-associated congenital dysplasia of the temporomandibular joint in mice.

The role of short stature homeobox 2 (shox2) in the development and homeostasis of the temporomandibular joint (TMJ) has been well documented. Shox2 is known to be expressed in the progenitor cells and perichondrium of the developing condyle. A previous study by our group reported that overexpression of shox2 leads to congenital dysplasia of the TMJ via downregulation of the Indian hedgehog (Ihh) signaling pathway, which is essential for embryonic disc primordium formation and mandibular condylar growth. To determine whether overexpression of Ihh may rescue the overexpression of shox2 leading to congenital dysplasia of the TMJ, a mouse model in which Ihh and shox2 were overexpressed (Wnt1-Cre; pMes-stop shox2; pMes-stop Ihh mice) was utilized to assess the consequences of this overexpression on TMJ development during post-natal life. The results showed that the developmental process and expression levels of runt-related transcription factor 2 and sex determining region Y-box 9 in the TMJ of the Wnt1-Cre; pMes-stop shox2; pMes-stop Ihh mice were similar to those in wild­type mice. Overexpression of Ihh rescued shox2 overexpression-associated reduction of extracellular matrix components. However, overexpression of Ihh did not inhibit the shox2 overexpression-associated increase of matrix metalloproteinases (MMPs) MMP9, MMP13 and apoptosis in the TMJ. These combinatory cellular and molecular defects appeared to account for the observed congenital dysplasia of TMJ, suggesting that overexpression of Ihh partially rescued shox2 overexpression­associated congenital dysplasia of the TMJ in mice.

[The characteristics of regulation of bone remodeling under inherent pathology of locomotive system in children].

The article presents the results of evaluation of clinical pathogenic value of hormones, markers of metabolism and indicators of mineral metabolism information of inherent pathology of locomotive system in children. The sampling included 29 children with dysplasia and deformation of lower extremities and 35 children without pathology of locomotive system. All children aged from 6 to 12 years. The serum levels of parathormone, calcitonin and 25(OH)-D3 were established using analytic module platform "Cobas 6000 SWA" (Roche Diagnostics, Switzerland). The content of somatotropic hormone in blood serum was evaluated using analyzer "Immulite One" (USA). The single examination of serum concentrations of total and ionized calcium, phosphorus, magnesium and activity of alkaline phosphatase was implemented using automatic analyzer "Cobas 6000 SWA" (Roche Diagnostics, Switzerland) and "HITACHI-912" (Roche Diagnostics corporation, Indianapolis, IN, USA). The activity of process of formation of and resorption of bone tissue was evaluated according content of PINP (N-terminal propeptid of type I collagen), osteocalcin and beta-CrossLaps (beta-isomerized carboxy-terminal cross-linking region of collagen type I) in blood serum. The module platform "Cobas 6000 SWA" (Roche Diagnostics, Switzerland) was used. The analysis of correlation interrelationships between qualitative indicators of bone metabolism and levels of regulative hormones in children with inherent pathology of locomotive system made it possible to clarify possible aspects of pathogenesis of disorders of bone remodeling as a result of induction of synthesis of somatotropic hormone and parathormone. The complex multi directional impact of these hormones results in uncoupling of synthesis processes and bone tissue resorption against the background of total slowing-down of bone remodeling. These occurrences apparently promote formation of dysplasia and deformation of bone skeleton.

Ischiovertebral dysplasia: a retrospective analysis of 30 consecutive cases pointing out the specifics and risks of the spine management.

STUDY DESIGN: A review of clinical publications, current knowledge, and recent developments regarding the etiology of ischiovertebral dysplasia was combined with a clinical review of the condition. OBJECTIVE: To acquaint orthopedic spine surgeons with identification patterns of ischiovertebral dysplasia in order to provide them with guidelines about spine management and which complications to expect. SUMMARY OF BACKGROUND DATA: Ischiovertebral dysplasia is a rare skeletal dysplasia that may appear in a sporadic fashion or be inherited with an autosomal dominant inheritance pattern. It is defined by the association of an ischiopubic ramus hypoplasia and a vertebral dysplasia. It leads to a specific spine deformity whose management and complications should be clarified. METHODS: Thirty consecutive patients from 0 to 31 years of age with ischiovertebral dysplasia were included from 5 centers specialized in congenital spinal deformities. Frontal and sagittal Cobb angles before treatment, natural history of the curves, therapeutic options, and their complications were systematically analyzed. RESULTS: All the patients had a vertebral dysplasia and 28 of them developed a spinal deformity. This deformity was an extremely severe thoracic kyphoscoliosis in 25 cases. The other deformities were a thoracolumbar scoliosis in 1 case and a thoracolumbar kyphosis in 2 cases. The management of the thoracic kyphoscoliosis was always challenging and complications included death by respiratory failure (3 cases) and neurological impairment (9 cases). CONCLUSION: Recognizing the occurrence of ischioverterbral dysplasia is very important to allow for dedicated treatment. The authors advocate preoperative distraction and circumferential fusion to prevent progression of the curve and to avoid the potentially fatal sequelae associated with this disorder. LEVEL OF EVIDENCE: 4.

Congenital osteofibrous dysplasia Campanacci: spontaneous postbioptic regression.

Osteofibrous dysplasia Campanacci is a rare benign bone tumor most frequently observed in young childhood. The exclusive localization in the tibia is very characteristic. The incidence of congenital primary bone tumors is an absolute rarity. We report a case of a newborn with a histologically proven osteofibrous dysplasia Campanacci at the tibia presenting a regular radiographic follow-up. After a small open biopsy and spontaneous minor fracture, the lesion rapidly remodeled within 1½ months and almost completely regressed with restutio ad integrum. Surgical intervention in this tumor entity at childhood age has been shown to have a high recurrence rate but due to lack of experience with newborns, guidelines do not exist. We analyze the radiologic and histologic differential diagnosis of juvenile adamantinoma and emphasize that congenital peripheral bone tumors should be treated conservatively when malignancy is excluded.

Embryonic ablation of osteoblast Smad4 interrupts matrix synthesis in response to canonical Wnt signaling and causes an osteogenesis-imperfecta-like phenotype.

To examine interactions between bone morphogenic protein (BMP) and canonical Wnt signaling during skeletal growth, we ablated Smad4, a key component of the TGF-ß-BMP pathway, in Osx1(+) cells in mice. We show that loss of Smad4 causes stunted growth, spontaneous fractures and a combination of features seen in osteogenesis imperfecta, cleidocranial dysplasia and Wnt-deficiency syndromes. Bones of Smad4 mutant mice exhibited markers of fully differentiated osteoblasts but lacked multiple collagen-processing enzymes, including lysyl oxidase (Lox), a BMP2-responsive gene regulated by Smad4 and Runx2. Accordingly, the collagen matrix in Smad4 mutants was disorganized, but also hypomineralized. Primary osteoblasts from these mutants did not mineralize in vitro in the presence of BMP2 or Wnt3a, and Smad4 mutant mice failed to accrue new bone following systemic inhibition of the Dickkopf homolog Dkk1. Consistent with impaired biological responses to canonical Wnt, ablation of Smad4 causes cleavage of ß-catenin and depletion of the low density lipoprotein receptor Lrp5, subsequent to increased caspase-3 activity and apoptosis. In summary, Smad4 regulates maturation of skeletal collagen and osteoblast survival, and is required for matrix-forming responses to both BMP2 and canonical Wnt.

The isolated mandibular ramus - a hitherto rarely described anomaly of the mandible. Pathogenesis and treatment.

INTRODUCTION: A very famous paper by Sam Pruzansky, published in 1969, was entitled "Not all dwarfed mandibles are alike". This is the topic of this paper: to describe the shape and discuss the possible pathogenesis of an extremely rare congenital dysplasia found in a unilaterally hypoplastic mandible, namely the isolated mandibular ramus. MATERIAL AND METHODS: A unique malformation of the lower jaw was found in more than 75 patients with developmental abnormalities of the mandible diagnosed and treated by the two authors in two different university hospitals over the last 40 years. We performed the following teratological experiments with laboratory rodents in order to try to understand the pathogenesis of this special dysplasia (and others): at first the normal development of the lower jaw was studied in rat and mouse foetuses. Then a variety of teratogenic drugs were applied to pregnant females and then the foetuses of these pregnancies were studied following Caesarian section. RESULTS: One rat foetus was identified which presented the identical dysplasia that had been noted in the patient described here. The dam pregnant with this foetus had been given 25 mg/kg bodyweight of 6-mercaptopurine on day 12 of pregnancy. The explanation found for the pathogenesis of this anomaly was deducted from the scientific literature regarding normal development of the mandibular condyle. CONCLUSION: The nucleus of the so-called secondary cartilage that will produce the ascending ramus (plus condyle and coronoid) is a separate growth centre which fuses a short time later with the dental bone which becomes the mandible proper by this fusion.

[Retrospective analysis on total hip arthroplasty for the treatment of developmental dysplasia of the hip in 29 adults].

OBJECTIVE: To study the results of the total hip arthroplasty (THA) in the treatment of developmental dysplasia of the hip (DDH) with severe osteoarthritis in adults. METHODS: From March 2004 to February 2011, 29 patients (32 hips) with DDH were treated by THA with an cementless cup. There were 11 males and 18 females,with an average age of 52.6 years (ranging from 37 to 73 years). Unilateral DDH occurred in 26 patients and bilateral DDH occurred in 3 patients. Based on the Crowe classification, there were 18 hips in 17 patients of type I ,7 hips in 6 patients of type II, 4 hips in 3 patients of type III, 3 hips in 3 patients of type IV. Except for 3 patients with bilateral DDH, the other patients' ill lower limbs were 1 to 6 cm shorter than the healthy lower ones. RESULTS: All the patients were followed up,and the duration ranged from 8 months to 5.3 years(averaged 3.7 years) without infection, dislocation, and sciatic nerves injury after the operation. One patient with proximal femoral fracture, intraoperation used wire binding, after 4 years of follow-up, fracture healed without evidence of prosthesis loosening. All grafts and subtrochanteric osteotomy healing were achieved. In 21 patients, the pain was completely relieved and the function of the hip joints was good. Five patients still had mild limping, but reduced significantly than preoperation. In 3 patients, the ill lower limbs were more than 1 cm shorter than the healthy lower ones and the other patients' ill lower limbs were less than 1 cm shorter than the healthy lower ones. Two patients' lower limbs were lengthened 4 to 5 cm. The Harris scores were 43.6 +/- 7.1 preoperatively and 86.7 +/- 5.3 postoperatively (P < 0.05). CONCLUSION: THA with deepening the medial wall of the acetabulum at the true acetabulum, according to different characteristics of Crowe classification, using different operation program, cementless cup in adult could obtain favorable results.

Congenital chondrodystrophy of unknown origin in beef herds.

Congenital chondrodystrophy of unknown origin (CCUO), often referred to as 'acorn calf disease' or congenital joint laxity and dwarfism (CJLD), has been reported in beef cattle in Canada, the United States, Europe, South Africa, New Zealand and Australia. An association of CCUO with grazing drought-affected pastures, feeding hay-only or silage-only diets or supplementation with apple pulp suggests a nutritional cause such as a mineral deficiency. This review compares published reports on CCUO in order to identify common features among outbreaks and to provide a basis for future research into the condition. A protocol for investigation of outbreaks is provided to improve the outcome of future comparisons.

Discoid meniscus associated with agenesis of the anterior cruciate ligament in an 8-year-old child.

Among the congenital anomalies involving the lateral compartment of the knee, the combination of both a discoid meniscus and agenesis of the anterior cruciate ligament (ACL) is extremely rare and probably underestimated due to the presence of a meniscofemoral ligament often mistaken for an intact ACL. The therapeutic management of such abnormalities is not univocal and highly depends on their clinical impact. We report on the observations of an 8-year-old boy presenting with a cystic formation on a lateral discoid meniscus associated with agenesis of the ACL and the presence of an anterior lateral meniscofemoral ligament.

Preimplantation genetic diagnosis (PGD)--prevention of the birth of children affected with endocrine diseases.

OBJECTIVE: To develop a reliable and accurate preimplantation genetic diagnosis (PGD) method in six families with endocrine diseases: persistent hyperinsulinemic hypoglycemia of infancy (PHHI), congenital adrenal hyperplasia (CAH) salt-wasting form, Sanjat-Sakati syndrome and multiple endocrine neoplasia 2A (MEN 2A). METHODS: For each disease a battery of at least four informative markers surrounding the tested gene were identified and for each family a protocol of multiplex fluorescent markers was developed and performed on single cells. RESULTS: PGD for PHHI was performed in three families. In family 1 two healthy children were born from different cycles, in family 2 three healthy children were born from two cycles, and in family 3 a healthy boy was born. For CAH in one family a healthy girl was born. One PGD cycle for Sanjat-Sakati resulted in a clinical pregnancy that was terminated due to high nuccal translucency (46X0). For one family with MEN 2A disease, the eighth PGD cycle resulted in birth of healthy twins. In all children genetic confirmation of the healthy status was performed. CONCLUSIONS: PGD is an effective method for preventing birth of affected children with endocrine disorders. Increasing the awareness of clinicians to the availability of these methods is most important.

Orthopaedic manifestations in a case of Lenz microphthalmia syndrome.

BACKGROUND: Lenz microphthalmia syndrome is an X-linked recessive disorder characterized by microphthalmia and dental, urogenital, and skeletal anomalies. This case report represents the first detailed account of congenital kyphoscoliosis in the Lenz microphthalmia literature. METHODS: We present a case of Lenz microphthalmia syndrome with progressive kyphosis, spinal stenosis, and late-onset tibia vara along with many of the typical features of the disorder. In addition, we provide insight into the syndrome by reviewing the existing Lenz microphthalmia literature. RESULTS: Congenital kyphoscoliosis that is prone to reoccurrence after posterior spinal fusion is an unusual entity that may be associated with Lenz microphthalmia. CONCLUSIONS: We recommend close monitoring and early surgical intervention with posterior spinal fusion for congenital kyphosis in patients diagnosed with Lenz microphthalmia syndrome. However, more data on similar patients are necessary to define the optimal treatment strategy. LEVEL OF EVIDENCE (FOR CLINICAL ARTICLES): Level V.