Rib Abnormalities Research Articles

Osteomyelitis of the ribs in children: a rare and potentially challenging diagnosis.

Rib osteomyelitis is rare in children and can mimic other pathologies. Imaging has a major role in the diagnosing rib osteomyelitis. To evaluate clinical presentation and imaging findings in children with rib osteomyelitis. We performed a retrospective (2009-2018) study on children with rib osteomyelitis verified by either positive culture or pathology. We excluded children with multifocal osteomyelitis or empyema necessitans. We reviewed medical charts for clinical, laboratory and pathology data, and treatment. All imaging modalities for rib abnormalities were evaluated for presence and location of osteomyelitis and abscess. We calculated descriptive statistics to compare patient demographics, clinical presentation and imaging findings. The study group included 10 children (6 boys, 4 girls), with an average age of 7.3years (range, 3months to 15.9years). The most common clinical presentations were fever (n=8) and pain (n=5). Eight children had elevated inflammatory indices (leukocytosis, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]). Localized chest wall swelling was found initially in six children and later in two more children. Rib osteomyelitis was suspected on presentation in only two children. All children had chest radiographs. Rib lytic changes were found on only one chest radiograph, in two of the four ultrasound studies, and in four of eight CTs. Bone marrow signal abnormalities were seen in all eight MRIs. In nine children the osteomyelitis involved the costochondral junction. Six children had an associated abscess. Staphylococcus aureus was cultured in eight children. Osteomyelitis was diagnosed based on pathology in one child with negative cultures. While rib osteomyelitis is rare, imaging findings of lytic changes at the costochondral junction combined with a history of fever, elevated inflammatory markers or localized soft-tissue swelling in the chest should raise suspicion for this disease.

Effects of egg exposure to atrazine and/or glyphosate on bone development in Podocnemis unifilis (Testudines, Podocnemididae)

This study was designed to investigate skeletal changes in Podocnemis unifilis embryos derived from artificially incubated eggs exposed to different concentrations of atrazine, glyphosate or atrazine and glyphosate mixture. Forty-two eggs were randomly allocated to one of seven trays containing vermiculite treated distilled water (control group) or the following solutions: 2 or 200 μg L-1 of atrazine (groups A1 and A2 respectively); 65 or 6500 μg L-1 of glyphosate (groups G1 and G2 respectively); 2 μg L-1 and 65 μg L-1 or 200 μg L-1 and 6500 μg L-1 of atrazine and glyphosate mixture (groups AG1 and AG2 respectively). Three eggs per tray were randomly collected on days 30 and 50 of the incubation period. Embryos were submitted to soft tissue diaphanization and stained with Alizarin red S or Alcian blue for morphological analysis of bone and cartilage tissues; histological analysis was performed to confirm ossification changes. Findings were compared between groups. Morphological changes were limited to sclerotic ring features and number of ribs. Malformations rates differed significantly (p < 0.05) between embryos in the control and treated groups A2, AG1 and AG2. Concurrent exposure to atrazine and glyphosate did not affect the presence or severity of embryonic malformations and was not associated with appendicular skeleton changes in P. unifilis embryos. However, further studies focusing on the axial skeleton with particular emphasis on rib abnormalities are warranted.

Short-term foetal immobility temporally and progressively affects chick spinal curvature and anatomy and rib development.

Congenital spine deformities may be influenced by movements in utero, but the effects of foetal immobility on spine and rib development remain unclear. The purpose of the present study was to determine (1) critical time-periods when rigid paralysis caused the most severe disruption in spine and rib development and (2) how the effects of an early, short-term immobilisation were propagated to the different features of spine and rib development. Chick embryos were immobilised once per single embryonic day (E) between E3 and E6 and harvested at E9. To assess the ontogenetic effects following single-day immobilisation, other embryos were immobilised at E4 and harvested daily between E5 and E9. Spinal curvature, vertebral shape and segmentation and rib development were analysed by optical projection tomography and histology. The results demonstrated that periods critical for movement varied for different aspects of spine and rib development. Single-day immobilisation at E3 or E4 resulted in the most pronounced spinal curvature abnormalities, multiple wedged vertebrae and segmentation defects, while single-day immobilisation at E5 led to the most severe rib abnormalities. Assessment of ontogenetic effects following single-day immobilisation at E4 revealed that vertebral segmentation defects were subsequent to earlier vertebral body shape and spinal curvature abnormalities, while rib formation (although delayed) was independent from thoracic vertebral shape or curvature changes.A day-long immobilisation in chicks severely affected spine and rib development, highlighting the importance of abnormal foetal movements at specific time-points and motivating targeted prenatal monitoring for early diagnosis of congenital scoliosis.

Risk Factors for Surgical Site Infections Following Vertical Expandable Prosthetic Titanium Rib (VEPTR) Surgery in Children

Study DesignCase-control study. ObjectivesTo identify risk factors for surgical site infections (SSIs) following vertical expandable prosthetic titanium rib (VEPTR) surgery in children. Summary of Background DataVEPTR surgery is a growth-sparing approach for early-onset scoliosis and chest or rib abnormalities. SSIs are an important complication following VEPTR surgery. We aimed to identify modifiable risk factors for SSIs following VEPTR surgery. MethodsChildren who underwent VEPTR surgery at a tertiary-care children’s hospital from January 2010 through November 2014 were included. SSIs following VEPTR implant or revision surgeries were identified. For each case patient, three control subjects matched by procedure type were randomly selected among those without infection. Patient and surgery-related risk factors were analyzed using conditional logistic regression. ResultsTwenty-six infections occurred in 22 subjects following 326 VEPTR surgeries (SSI rate: 8.0%). The infection rate was greater among implant than revision surgeries (15.5% vs. 4.5%; p<.001). Methicillin-susceptible Staphylococcus aureus was the most common pathogen (50% of infections). On multivariate analysis, VEPTR SSI infections were associated with male gender (OR 3.5, 95% CI 0.9-13.2), assisted feeding (OR 4.5, 95% CI 1.0-20.3), administration of preoperative antibiotics more than 30 minutes before surgery (or >60 minutes for vancomycin) (OR 6.9, 95% CI 1.2-39.0), and an intraoperative temperature less than 35.0°C (OR 4.3, 95% CI 0.8-23.7). ConclusionsAdministration of preoperative antibiotics closer to the time of surgery may reduce the risk of SSI in children undergoing VEPTR surgery. Further study is needed to determine the optimal timing of antibiotic prophylaxis for children undergoing spinal surgery. Level of EvidenceLevel III.

Maternally inherited 133kb deletion of 14q32 causing Kagami–Ogata syndrome

We present a case of a newborn female with multiple anomalies demonstrating that the causes of imprinting disorders rely not only on the parent-of-origin of the chromosomal aberrations, but also the scope of genes contained in the imprinted region. The newborn female presented with prenatal polyhydramnios, neonatal respiratory distress, distal contractures, abdominal hernia, bell-shaped thorax, and abnormal ribs. The neonate required mechanical ventilation due to apnea, underwent surgery for laryngomalacia, and showed development delay by age 11 months. Chromosomal microarray analysis identified a single copy number loss in chromosome region 14q32.2q32.31, containing genes that are differentially expressed based on parent-of-origin. Microarray analysis also confirmed the identical deletion in the patient's mother, who was reported to be normal. Additional molecular analyses determined the exact size and breakpoints of the deletion as well as methylation states in both the patient and her mother. The maternally transmitted deletion was responsible for Kagami-Ogata syndrome in the patient.

Diagnosis and Management of Paget-Schroetter Syndrome in Children: An Institutional Experience

Background: Paget-Schroetter Syndrome (PSS), also known as venous thoracic outlet syndrome or effort-induced upper extremity deep vein thrombosis, is a rare condition that occurs secondary to impingement of the subclavian vein by the overlying cervical ribs, long transverse processes of the cervical spine, musculo-fascial bands, or clavicular or first rib abnormalities. PSS often affects otherwise healthy and athletic individuals with a history of repetitive overhead activities. Given the paucity of published pediatric data, making evidence-based recommendations on appropriate therapeutic strategies is challenging.Objective: The principal objective of this single-institution study was to review the presentation, management, and outcomes of pediatric patients treated for PSS at Nationwide Children's Hospital (NCH) over a six-year period (January 1, 2010 to December 31, 2016).Methods: The study was approved by the Institutional Review Board at NCH. The Electronic Data Warehouse was used to identify patients diagnosed with PSS during the 6-year study period using modified ICD-9-CM codes. Eligible subjects were defined as children under the age of 21 who presented with an unprovoked upper extremity deep vein thrombosis (DVT) and had evidence of compression of the subclavian vein at the level on the thoracic outlet on dynamic imaging. Baseline demographic data, diagnostic and therapeutic details, and available follow-up information was abstracted from patient charts. Eligible subjects were also mailed a previously validated pediatric post-thrombotic syndrome (PTS) self-report instrument and a self-report health-related quality of life (HRQoL) instrument (PedsQL 4.0). All data were summarized and presented using descriptive statistics. Comparisons were made using nonparametric statistical methods.Results: The study cohort consisted of 21 subjects (11 female). Median age at DVT diagnosis was 16.3 (range 13.7-18.2) years. Subjects presented to NCH a median of 2 (range 0-34) days after symptom onset. Eighteen subjects (86%) reported repetitive exercise or overuse activity prior to diagnosis. Twelve subjects (57%) had evidence of congenital/acquired thrombophilia (Table 1). All subjects were treated with anticoagulation for a median duration of 3.2 (range 1.4-8.6) months. Nine subjects (43%) were also treated with catheter-directed and/or pharmaco-mechanical thrombolysis, and six of these subjects additionally underwent balloon angioplasty. All 21 subjects underwent decompressive surgery (first or cervical rib resection) a median of 7.7 (range 2-63.2) weeks after symptom onset. Four subjects (19%) experienced surgical complications, including minor bleeding/hematoma formation (3), pneumothorax (3), and winged scapula (1). Only 2/14 subjects diagnosed before 2014 underwent thrombolytic therapy, whereas all (7/7) subjects diagnosed after 2014 underwent thrombolysis. The subjects who did not undergo thrombolysis were not significantly different from those who did, except for the presence of a thrombophilia (p=0.02). Of the twelve subjects who did not undergo thrombolysis, eleven (92%) had complete/partial resolution of their DVT and one (8%) had no resolution on most recent imaging. Of the nine subjects who received thrombolysis, 100% had complete/partial resolution of their DVT on most recent imaging. We are currently analyzing data on PTS and HRQoL.Discussion: Herein, we report one of the largest pediatric cohorts of PSS. All subjects received anticoagulation and underwent decompressive surgery. Additionally, 9/21 subjects underwent catheter-directed and/or pharmaco-mechanical thrombolysis. 20/21 subjects had complete/partial resolution of the DVT on most recent imaging. Our single-institution study suggests that high rates of thrombus resolution may be achieved in children with PSS with anticoagulation and decompressive surgery, with or without thrombolytic therapy. Larger, prospective studies are needed to confirm our findings and further examine the relationship between treatment and outcomes. [Display omitted] DisclosuresO'Brien:Bristol Myers Squibb: Other: study of direct oral anticoagulant in prevention of pediatric VTE, Research Funding; Glaxo Smith Kline: Other: DSMB for Arixtra Study in Pediatric VTE; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: advisory board - von Willebrand Disease diagnosis & management; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: advisory board - VWD diagnosis and management; Pfizer: Consultancy, Other: study of direct oral anticoagulant in treatment of pediatric VTE. Kumar:CSL Behring: Consultancy; Bayer: Consultancy.

VEPTR Implantation to Treat Children With Early-Onset Scoliosis Without Rib Abnormalities: Early Results From a Prospective Multicenter Study.

Thoracoplasty and insertion of vertical expandable prosthetic titanium rib (VEPTR) for thoracic and spine distraction has been found to be effective in the treatment of early-onset scoliosis (EOS) with ribs anomalies and congenital vertebral anomalies. The aim of this study was to evaluate the efficacy of VEPTR in preventing further progression of scoliosis without impeding spinal growth in children with progressive EOS without rib abnormalities. This is a prospective, multicenter, observational cohort study. Erect radiographs were analyzed for coronal and sagittal curve and height measurements at preimplant, immediate postoperative, and at 2-year follow-up. Sixty-three patients met inclusion: 35 males and 28 females. Mean age at time of implantation was 6.1±2.4 years. Etiologies included congenital (n=6), neuromuscular (n=36), syndromic (n=4), and idiopathic (n=17). The mean follow-up was 2.2±0.4 years. Scoliosis (72±18 degrees) decreased after implant surgery (47±17 degrees) followed by slight increase at 2-year follow-up (57±18 degrees), P<0.0001. Kyphosis (48±22 degrees) also showed significant decrease after implantation (40±14 degrees), but increased after 2 years (48±16 degrees), P<0.0001. Coronal spine height measurements including T1-T12 (15.7±3 cm) and T1-S1 (25±6 cm) showed significant increases after implantation surgery (17.7±4 cm and 28.6±6 cm, respectively) and at 2 years (18.4±4 cm and 29.1±5 cm, respectively), P<0.0001. The increase in coronal spine height represented 144% of expected age-matched T1-T12 growth and 193% of expected age-matched T1-S1 growth. Similarly, sagittal spine length of T1-T12 and T1-S1 increased from 16.9±2.7 cm and 27.1±3.9 cm, respectively preoperatively to 19.7±3.5 cm and 31.9±5.1 cm, respectively at 2-year follow-up, P<0.0001. The instrumented spine segment continued growth from 25.8±5.2 cm after implantation to 27.4±5.3 cm at 2-year follow-up, P<0.0001. Thirty-one patients (49%) had at least 1 complication with total of 58 complications. At 2-year follow-up, VEPTR was effective in treating EOS without rib abnormalities with 86% of patients having an improvement in scoliosis and 94% of patients having an increased spinal height as compared with preoperative values. This study proved that spine continues to grow after VEPTR instrumentation during the distraction phase. This amount of growth represents about 40% for T1-T12 and 31% for T1-S1 spine of the expected age-matched growth based on Dimeglio reference numbers. We find this growth important as it proves continuous spine growth with VEPTR treatment. Level II.

Oropharyngeal teratoma in association with a diaphragmatic hernia

Abstract Pediatric germ cell tumors (GCT) rarely occur in the head and neck region and they are rarely associated with congenital anomalies. A 17 month old girl presented with a history of cough and change in voice for one month. Her chest x-ray and cross sectional imaging was suggestive of a mediastinal mass, right diaphragmatic hernia, and rib abnormality. Serologic and biomarkers were all negative for tumors. Surgical resection occurred with clear margins revealing a mass arising from the left hypopharnx via a pedunculated stalk. Histopathology was consistent with a mature teratoma including significant amounts of parathyroid tissue. She remains tumor free at 18 months follow up. To the best of our knowledge our patient is the third case in which a diaphragmatic hernia was reported in association with hypopharyngeal teratoma and our patient is the first to survive; this provides an opportunity to counsel families when this association is encountered.

VEPTR Treatment of Early Onset Scoliosis (EOS) in Children without Rib Abnormalities: Long-Term Results of a Prospective, Multicenter Study

A prospective, multicenter study demonstrating the long-term efficacy of VEPTR treatment in EOS without rib abnormalities.

Short stature, unusual face, delta phalanx, and abnormal vertebrae and ribs in a girl born to half‐siblings

Delta phalanx is a rare abnormality typically associated with additional features. We describe a patient with a phenotype resembling Catel-Manzke syndrome, but with delta phalanx and abnormal vertebrae and ribs. The patient was the only child of half siblings born with a marked prenatal growth deficiency. At 10 years of age, she had a short stature, long face, long and tubular nose with small alae nasi, high palate, short and broad thorax, and short index fingers with radial deviation. There were hyperpigmentations following Blaschko's lines. Radiology showed a proximal delta phalanx in the index finger of hands, abnormal vertebrae, and fused and small ribs. GTG-Banding karyotype and microarray analysis yielded normal results. Exome sequencing identified 25 genes that harbored homozygous variants, but none of these is assumed to be a good candidate to explain (part of) the phenotype. The here described patient may have a new condition, possibly following an autosomal recessive pattern of inheritance, although due to the high degree of consanguinity a compound etiology of the phenotype by variants in various genes may be present as well.

Poland’s syndrome

Poland’s syndrome is a rare congenital condition classically characterized by partial or complete absence of chest muscles on one side of the body and usually webbing of the fingers of the hand on the same side. There may also be rib (aplasia or hypoplasia) and chest bone abnormalities, which may be noticeable due to less fat under the skin. Breast and nipple abnormalities may also occur, and underarm hair is sometimes sparse or abnormally placed. In most cases, the abnormalities in the chest area do not cause health problems or affect movement. Poland’s syndrome most often affects the right side of the body and occurs more frequently in males than in females. The etiology is unknown; however, interruption of the embryonic blood supply to the arteries that lie under the collarbone (subclavian arteries) is the prevailing theory. There are many methods of operative correction because of the polymorphic clinical features of this syndrome. We gathered data on the etiology, pathogenesis, and clinical presentation of Poland’s syndrome and reviewed the existing surgical treatment options.

Clinical presentation and management of arterial thoracic outlet syndrome

ObjectiveArterial thoracic outlet syndrome (TOS) is a rare condition characterized by subclavian artery pathology associated with a bony abnormality. This study assessed contemporary clinical management of arterial TOS at a high-volume referral center. MethodsA prospectively maintained database was used to conduct a retrospective review of patients undergoing primary or reoperative treatment for arterial TOS during an 8-year period (2008 to 2016). Presenting characteristics, operative findings, and clinical and functional outcomes were evaluated. ResultsForty patients underwent surgical treatment for arterial TOS, representing 3% of 1401 patients undergoing operations for all forms of TOS during the same interval. Patients were a mean age of 40.3 ± 2.2 years (range, 13-68 years), and 72% were women. More than half presented with upper extremity ischemia/emboli (n = 21) or posterior stroke (n = 2), including eight that had required urgent brachial artery thromboembolectomy. The presentation in 17 (42%) was nonvascular, with 11 having symptoms of neurogenic TOS and six having an asymptomatic neck mass or incidentally discovered subclavian artery dilatation. All patients underwent thoracic outlet decompression (25 supraclavicular, 15 paraclavicular), of which there were 30 (75%) with a cervical rib (24 complete, 6 partial), 5 with a first rib abnormality, 4 with a clavicle fracture, and 1 (reoperation) with no remaining bone abnormality. Subclavian artery reconstruction was performed in 70% (26 bypass grafts, 1 patch, 1 suture repair), and 30% had mild subclavian artery dilatation (<100%) requiring no arterial reconstruction. Mean postoperative length of stay was 5.4 ± 0.6 days. During a mean follow-up of 4.5 ± 0.4 years (range, 0.9-8.1 years), subclavian artery patency was 92%, none had further dilatation or embolism, and chronic symptoms were present in six (4 postischemic/vasospasm, 2 neurogenic). Functional outcomes measured by scores on the 11-item version of the Disability of the Arm, Shoulder and Hand Outcome Measure improved from 39.1 ± 3.8 to 19.2 ± 2.7 (P < .0001). ConclusionsThis relatively large single-institution series demonstrates the diverse clinical presentation of arterial TOS coincident with a spectrum of bony and arterial pathology. Current surgical protocols can achieve excellent outcomes for this rare and often complicated condition.

Sprengel Deformity and Omovertebral Bone

Abstract: Sprengel deformity is the most common congenital abnormality of the shoulder girdle, resulting from an elevated, dysplastic, and variably fixed scapula. It has cosmetic implications that make it readily identifiable, and may be also associated with functional impairment. It may associate with other structural abnormalities, such as the presence of an omovertebral bone, or bar. When present, it adds to the immobility of the scapula. We present the images relating to the case of a 8-year old boy, with previous history of spina bifida and hydrocephalus. He presented with scapular elevation and limitation of shoulder motion, and was diagnosed with a Cavendish 4 type Sprengel deformity of the scapula. An associated omovertebral bone connecting the superomedial angle of the scapula and cervical spine was detected on CT scan. 3D reconstruction of the images allowed accurate definition of the deformity and the relations of the abnormal bone. The deformity was afterwards surgically treated, by means of a clavicle osteotomy, omovertebral bone resection, and Woodward procedure. The patient had an eneventful recovery, and had satisfactory functional and cosmetic gains.Case Presentation An 8-year old boy, previously surgically treated for hydrocephalus and spina bifida, was referred to our Paediatric Hospital for evaluation of the fixed elevation and limited motion of the right shoulder (Figure 1). A clinical diagnosis of Sprengel Deformity was made, being a Cavendish 4 grade [1] in severity. In the investigations ordered scapular elevation was confirmed and the presence of an anomalous omovertebral bone was noted between the superomedial angle of the scapula and C6 spinous process (Figure 2). Surgery was proposed, and a clavicular osteotomy, omovertebral bone resection and Woodward procedure were performed (Figure 3). Sprengel Deformity is a complex congenital pectoral girdle deformity, with cosmetic and functional implications. It is associated with other deformities, such as spinal dysraphism (as spina bifida in this case), scoliosis, and rib and vertebral segmentation abnormalities, such as Klippel-Feil. [2] The omovertebral bone is an anomalous bone connecting the elevated scapula to the cervical spine, being called omovertebral bar should it be fused between them. It contributes to the immobility of the scapula and the functional impairment, and its resection should be performed if surgical treatment is pursued [1]. It may not be always visible on plain x-rays, and so more advanced imaging is recommended prior to surgery for assessment and planning, such as CT (ideally with 3D reconstruction) [3]. Clavicle osteotomy is advised either in the treatment of associated clavicle deformity, or as to lower the chances of brachial plexus injury [4] in higher grade corrections.The child in the case described had an uneventful postoperative course, and received rehabilitation treatment, having later satisfactory functional and cosmetic gains. Conclusion: Sprengel deformity is a complex shoulder girdle abnormality. If surgical treatment is considered, associated abnormalities such as the omovertebral bone should be sought - CT scan with 3D reconstruction is advised. When found, omovertebral bone should be excised during surgery

Bifid ribs: a comprehensive review

Bifid or bifurcated ribs are a rare anatomical anomaly that accounts for approximately 28% of known rib abnormalities. Bifurcation always occurs at the sternal end of the rib and its two extremities are joined to a bifid costal cartilage. The presence of bifid rib is frequently accompanied by other anomalies, although this does not necessarily imply that it cannot occur as an isolated anomaly. The clinical significance of the latter has not been established. There have not been many studies done to investigate bifid rib closely aside from individual case reports, presumably due to the condition’s extremely low incidence. However the detection of bifid ribs, though mostly incidental, has been proven advantageous for an early and wellrounded diagnosis It has also revealed significant preventive benefits especially in the pediatric patient population. This review is written to provide a comprehensive summary of what is known about bifid ribs and incorporate substantial findings from clinical cases that have been reported in past literature.

Prevalence and pattern of cervical rib, transversomegaly and other vertebral anomalies in normal adult cervical spine in Kumaon region of Uttarakhand, India

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; A supernumary rib from seventh cervical vertebra is called cervical rib and is a common anomaly. Its true prevalence is not validated as most of these are asymptomatic thus do not get diagnosed. Its incidence has been reported in several geographic regions and ethnic clusters. Most of the studies rely on radiological data collected from evaluation of chest or neck radiographs of defined numbers.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; A similar study to ascertain its presence and incidence, apart from sexual and morphological pattern is required for Kumaon region of Uttarakhand, India. The present study reports data extracted from study of 1500 radiographs and evaluating them for presence of cervical rib and other abnormalities. Demographic and other relevant details were noted.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Most of the cases were female and almost all cases of cervical rib or transversomegaly were bilateral. 0.8% and 1.4% cases were noted for cervical rib and transversomegaly respectively. Apart from it, 4 cases of vertebrae fusion and one case of hemi-vertebra leading to cervical scoliosis was also noted.&lt;/p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; The prevalence of cervical rib was comparable to other studies considering the sample size. The calculation of true incidence however will require multi-discipline collaboration and robust data. This study, however, is important for further work in this regard and adds value to existing literature.

Disordered vertebral and rib morphology in pudgy mice. Structural relationships to human scoliosis.

Normal and abnormal vertebral development have been studied over the past 200 years at increasing levels of resolution as techniques for biological investigation have improved. Disordered development of the axial skeleton from the early embryonic period on leads to structurally malformed vertebrae and intervertebral discs and ribs causing the severe deformities of scoliosis, kyphosis, and kyphoscoliosis. Developmental malformation of the axial skeleton therefore has led to considerable biological and clinical interest. This work will detail our studies on the structural deformities of the vertebral column and adjacent ribs in the pudgy mouse [1] caused by mutations in the delta-like 3 (Dll3) gene of the Notch family [2]. While gene abnormalities in the pudgy mouse have been outlined, there has been no in-depth assessment of the histopathology of the pudgy vertebral and rib abnormalities that this study will provide. In addition, although congenital scoliosis has been recognized as a clinical problem since the mid-nineteenth century (1800s) [3] and accurately defined by radiography since the early twentieth century (1900s) [4-6], there have been few detailed histopathologic studies of human cases. We will also relate our histopathologic findings in the pudgy mouse to the histopathology of human vertebral and rib malformations in clinical cases of congenital scoliosis, one of which we defined in detail previously [7].

Development of the bones and synovial joints in the rat model of the VATER association

The adriamycin-induced rat model of the Vertebral, Anorectal, Tracheo-Esophageal, Radial and Renal (VATER) association produces a variety of vertebral, rib, and limb abnormalities. This study was designed to document accurately the nature of these abnormalities and to determine whether synovial joints are affected. Fetuses from pregnant Sprague Dawley rats that had received intraperitoneal injections of 1.75mg/kg of adriamycin on days 6–9 or 10–13 of gestation were harvested. Double-stained skeletal preparations and histological sections were examined for vertebral, rib, and limb anomalies. The incidence of anomalies was high in the group treated on gestational days (GD) 6–9, while it was low in the GD 10–13 group. The length and thickness of the long bones were reduced, with bowing and reduction in their endochondral ossification. Sirenomelia occurred in the group treated on GD 6–9, and was often associated with a short tail and anal atresia. The joint cavities, and intr a-articular structures such as menisci and the cruciate ligaments developed normally from the mesenchymal interzone. These data indicate that adriamycin inhibits skeletal growth and differentiation without any interference in the differentiation of the mesenchymal interzone, thus producing normal synovial joints.

A relatively mild skeletal ciliopathy phenotype consistent with cranioectodermal dysplasia is associated with a homozygous nonsynonymous mutation in WDR35.

Ciliopathies are a class of clinically and genetically heterogeneous disorders characterized by deficits of the primary cilium, an important organelle for cellular signaling and development. Here we report on a patient from a consanguineous family presenting with renal cysts, short stature, distinctive facial features, missing teeth, brachydactyly, narrow chest, and abnormal ribs. His phenotype resembled a skeletal ciliopathy and the initial clinical differential diagnosis included Jeune thoracic dystrophy and cranioectodermal dysplasia. Due to the presence of parental consanguinity, a homozygous recessive mutation was the suspected cause and homozygosity mapping was used to direct candidate gene sequencing. WDR35, an intraflagellar transport protein previously associated with cranioectodermal dysplasia, the more severe short rib polydactyly syndrome type V and recently Ellis van Creveld syndrome, is present within a region of homozygosity and sequencing of all coding exons identified a novel homozygous nonsynonymous variant, p.Trp1153Cys. This variant affects a highly conserved tryptophan residue, is predicted to be deleterious, and is the most distal mutation yet reported in WDR35. This case expands the spectrum of phenotypes caused by WDR35 mutations, which we review herein.

Prenatal diagnosis of sirenomelia by two-dimensional and three-dimensional skeletal imaging ultrasound.

This study sought to evaluate the contribution of two-dimensional ultrasound (2D-US) and three-dimensional skeletal imaging ultrasound (3D-SUIS) in the prenatal diagnosis of sirenomelia. Between September 2010 and April 2014, a prospective study was conducted in a single referral center using 3D-SUIS performed after 2D-US in 10 cases of sirenomelia. Diagnostic accuracy and detailed findings were compared with postnatal three-dimensional helical computed tomography (3D-HCT), radiological findings and autopsy. Pregnancy was terminated in all 10 sirenomelia cases, including 9 singletons and 1 conjoined twin pregnancy, for a total of 5 males and 5 females. These cases of sirenomelia were determined by autopsy and/or chromosomal examination. Initial 2D-US showed that there were 10 cases of oligohydramnios, bilateral renal agenesis, bladder agenesis, single umbilical artery, fusion of the lower limbs and spinal abnormalities; 8 cases of dipus or monopus; 2 cases of apus; and 8 cases of cardiac abnormalities. Subsequent 3D-SUIS showed that there were 9 cases of scoliosis, 10 cases of sacrococcygeal vertebra dysplasia, 3 cases of hemivertebra, 1 case of vertebral fusion, 3 cases of spina bifida, and 5 cases of rib abnormalities. 3D-SUIS identified significantly more skeletal abnormalities than did 2D-US, and its accuracy was 79.5% (70/88) compared with 3D-HCT and radiography. 3D-SUIS seems to be a useful complementary method to 2D-US and may improve the accuracy of identifying prenatal skeletal abnormalities related to sirenomelia.

Risk of metastasis among rib abnormalities on bone scans in breast cancer patients.

Bone scan abnormalities, especially rib lesions, are often confusing for physicians due to a high number of false-positive lesions. This study investigated risk factors that are associated with bone metastasis in 613 breast cancer patients with bone scan abnormalities. Significantly increased rates of bone metastasis were observed in patients with multiple lesions, large tumor sizes, and lymph node involvement. In addition, patients with concurrent lesions of rib and other sites exhibited a significant higher rate of metastatic disease compared to those with other site lesions (P = 0.009). In the subset of 324 patients with rib abnormalities, the rate of metastasis was extremely low in patients with pure rib lesions (1.2%; 95% CI: 0.1%–4.1%). Concurrent lesions of rib and other sites were more likely to be rib metastasis compared to pure rib lesions (P < 0.001). Moreover, multiple rib lesions and lesions located on bilateral ribs were more likely to be rib metastasis (P < 0.001). Our data suggest that patients with pure rib abnormalities could be recommended for follow-up only. However, if concurrent lesions of rib and other sites were detected on bone scans, additional radiological examinations should be performed to patients.