Bone Hypertrophy Research Articles

Klippel-Trenaunay syndrome as a rare cause of chronic thromboemboembolic pulmonary hypertension

Klippel-Trenaunay syndrome (KTS) is a congenital disorder characterized by cutaneous capillary malformations, soft tissue and bone hypertrophy, and multiple capillary, venous or lymphatic malformations. KTS is associated with recurrent thromboembolic events. We reported herein five cases of chronic thromboembolic pulmonary hypertension (CTEPH) associated with KTS (age minimum–maximum 26–50 years old, 3 males/2 females). Hemodynamics showed severe pulmonary hypertension (PH) with pulmonary vascular resistance ranging from 5.6 to 18.3 Wood units (WU), associated with marked clinical impairment (NYHA functional class III or IV in 4 patients). Computed tomography (CT) of the chest and pulmonary angiography confirmed proximal CTEPH accessible to surgical intervention in one patient and distal forms of CTEPH in 4 patients. Evolution after pulmonary endarterectomy showed hemodynamic normalization, while the patients with distal CTEPH had severe outcomes with 2 early deaths after PH diagnosis (44 and 35 months respectively). One patient with distal CTEPH was still alive 16 years after diagnosis on specific PH therapy and one was transplanted after 15 years because of right heart failure (death after 12 months). Histological analysis of the lung explants showed typical chronic thromboembolic material specific for CTEPH. In conclusion, KTS may be complicated by severe CTEPH requiring careful anticoagulation and multidisciplinary follow-up in expert centers to screen for disease potentially accessible to endarterectomy. In the modern management era of CTEPH, balloon pulmonary angioplasty will certainly be an interesting option in patients with inoperable disease.

Venous malformation of lower limb with hypertrophy of limb, early terminalization of hair and hyperhidrosis

Vascular anomalies are the commonest developmental disorders. Venous malformations (VM) result due to dysmorphogenesis in the development of veins. Most commonly these disorders are localized to skin and subcutaneous tissue. Deeper venous malformation may affect the underlying muscle, bone and joints. Early terminalization of hair and increased sweating in VM plaque has been rarely reported. The present study deals with the case of a 15-year-old boy who had VM involving skin, subcutaneous tissue and bones with terminal hair and increased sweating over the plaque. Radiological examination showed bone hypertrophy with slow flow channels and phleboliths due to superficial and deep VM. He was treated with ethanol sclerotherapy.

Cancer Risk in Klippel-Trenaunay Syndrome.

Background: Klippel-Trenaunay syndrome (KTS) is an overgrowth syndrome defined by capillary/venous/lymphatic malformations (CVLM) with soft tissue and/or bone hypertrophy. Whether KTS predisposes to cancer is not clear. Methods and Results: We surveyed members of the K-T Support Group (KTSG) and reviewed PubMed for "Klippel Trenaunay Syndrome" or "CVLM" and "cancer." Individuals with cancer were reviewed for confirmation of KTS, tumor type, location, and age at presentation. Of 223 KTSG respondents, 24 (10.8%) reported 26 malignancies or benign brain tumors (diagnosed from 6 months to 68 years of age, median 41 years), including 3 who were younger than 18 years (2 with Wilms tumor). Nine of twenty-six cancers were basal cell carcinomas (4% of respondents). From 475 articles, we identified 11 cancers or brain tumors in 10 individuals with KTS. Four of these were in children (Wilms tumor n = 2; rhabdomyosarcoma n = 1; serous borderline tumor n = 1). Tumors in adults included basal cell carcinoma (n = 1), squamous cell carcinoma of skin (n = 2), and angiosarcoma, Hodgkin disease, glioblastoma, malignant hemangiopericytoma in one patient each. Ulceration or lymphedema associated with VLM or capillary malformations were associated with some basal cell or squamous cell carcinomas and angiosarcomas. Conclusions: The risk of embryonal cancer other than Wilms tumor in children with KTS does not appear to be higher than in the general population. Wilms tumor incidence is under 5%, and routine surveillance is not indicated. In adults, particular attention should be paid to skin in the area of malformations. These conclusions may not apply to all overgrowth syndromes with vascular malformations.

Correlation between the effect of increasing body weight with plantar pressure and ankle-knee radiographic angle parameters changes

Background: Understanding the biomechanical structure of the body is important to preventing and treating the musculoskeletal system problems. The increase in body mass index contributes to the elevated peak plantar pressure and decreased longitudinal arch of the foot. This condition, consequently, may cause mal-alignment of the lower extremity, leading to promote cartilage breakdown, osteophyte formation, subchondral bone hypertrophy, lead to progression of knee joint destruction and functional deficits. Objective: The aim of the study was to examine the correlation between body weight, plantar pressures, ankle and knee angle measurement parameters. Methods: The research study sample included 30 female who met inclusion and exclusion criteria. In order to evaluate the structural characteristic of plantar foot, we used the blueprint method on bare-foot and also when carrying 15 and 25 kilogram of load. Furthermore, to measure knee-angle parameters, we also performed a bilateral standing radiograph approach of lower extremity. Results: This study showed a significant correlation between BMI/Body mass index and HW/heel width (p = 0,00) with low positive correlation for both sides. Furthermore, BMI and PAW/plantar arch width (p = 0,00) showed a moderate positive correlation for both sides. In contrast to that, BMI and MFA/mid-foot area (p = 0,00) showed a moderate positive correlation for the right side but low positive correlation for the left side. Another measurement such as BMI and AI/arch index (p = 0,00) had a strong positive correlation on the right side and moderate positive correlation on the left side. Moreover, BMI and AAL/Ankle angle alignment (p = 0,00) revealed a strong positive correlation for both sides, BMI and XCTP/trans-condylar tibial plateau angle (p < 0,05) had a low positive correlation for both sides, meanwhile BMI and AA/ankle angle (p = 0,00) showed a low positive correlation for both sides. Conclusion: Increasing axial load was statistically significant correlated with increasing plantar pressure and ankle-knee radiographic angle parameter. The results also revealed that increasing axial load was found to have strong correlation to the arch index (AI) and ankle angle alignment (AAL). It was a compensatory phenomenon, which can cause structural disturbances and function of the lower limb.

Kyphoscoliosis with Klippel-Trenaunay syndrome: a case report and literature review

BackgroundKlippel-Trenaunay syndrome (KTS) is a rare congenital syndrome characterized by the triad of venous varicosities, capillary malformations and limb hypertrophy. However, KTS may rarely occur in combination with kyphoscoliosis.Case presentationWe presented an 18-year-old female with KTS and kyphoscoliosis. Hypertrophy of bone and soft tissue affected her left face, trunk and lower limb. Moreover, the patient is associated with subacute thyroiditis, vitamin D deficiency and iron deficiency anemia, high level of D-dimer, swollen tonsil, kyphoscoliosis and Chiari-I-malformation without syringomyelia. A posterior correction and spinal fusion from T10 to L5 levels were performed for this patient. The lumbar curve was corrected from 105° to 60° and the kyphosis improved from 58° to 26°. The distance of trunk shift decreased from 10 cm to 1.4 cm. There were no thrombotic events occurred. At the 8th month follow-up, there was no significantly change of the curve in the coronal and sagittal radiographs. During the 31-month follow-up, the patient did not experience any discomfort. And her general appearance did not have any change until the last follow-up. However, she refused to take radiograph for worrying about radiation.ConclusionsKTS is a rare disease with classic clinical triad. However, it can also have other different features, including kyphoscoliosis, elevated D-Dimer, vitamin D deficiency and iron-deficiency anemia. These issues should be taken into consideration when planning treatment for kyphoscoliosis in KTS patients.

Increased subchondral bone thickness in hips with cam-type femoroacetabular impingement.

Increased thickness of subchondral acetabular bone with associated articular cartilage thinning in hips with femoroacetabular (FAI) cam impingement has been observed on magnetic resonance imaging (MRI). Dynamic attrition by the cam deformity moving into the acetabulum may potentiate trans-articular shear stresses thus causing these subchondral bone changes. We aimed to quantify the hypertrophic changes of subchondral acetabular bone in patients with cam-type FAI. MRI studies were performed on an asymptomatic population of young Swiss army recruits. Subjects underwent clinical examination and completed questionnaires before undergoing an MRI of the hip. Cam deformities were graded and the dimensions of the acetabular subchondral bone quantified. Univariate linear regression was used to determine the association between the presence of cam deformities and the degree of subchondral acetabular sclerosis. There was a strong association between cam deformities and the thickness, area and shape of subchondral sclerosis. The main increase in hypertrophy was observed in the antero-superior acetabulum where impingement typically occurs. The subchondral sclerosis was 0.66 mm thicker in cam-type deformities than in hips without cam-type deformities (95% CI, 0.38-0.93, p value < 0.001). Mechanical stress in the antero-superior acetabular area is elevated in hips with a cam-type deformity. The study supports the concept that cam-type deformity induced stress leads to hypertrophy of subchondral acetabular bone in the area of impingement. This is collocated with the clinically observed cartilage damage caused by the cam mechanism.

Radiological Aspect of Klippel-Trénaunay Syndrome: A Case Series With Review of Literature.

Klippel-Trénaunay syndrome (KTS) is a rare angio-osteo-hypertrophic syndrome characterized by vascular malformations, soft tissue and/or bone hypertrophy, and varicose veins. For the purpose of describing the imaging findings and elucidating the role of medical imaging in the diagnosis and assessment of patient with KTS, we have reviewed the imaging data of 14 KTS patients. The imaging features on different imaging modalities were analyzed. Unilateral lower limb involvement was evident in 71% of cases (n=10) and bilateral but asymmetric lower limb involvement in the remaining 29% of cases (n=4). The most commonly depicted imaging features were varicosities in 93% (n=13), muscle hypertrophy in 79% (n=11) and venous anomalies in 64% (n=9). Other less common imaging findings included lymphedema in 29% (n=4), arterial malformations 29% (n=4), soft tissue hemangiomas 21% (n=3), pelvic and thigh phleboliths 21% (n=3), venous aneurysms 21% (n=3), bone abnormalities 14% (n=2) and lymphadenopathy 14% (n=2). A severe unilateral lower limb deformity resulting in contractures and muscle atrophy of the whole limb was depicted in 1 case. The pathognomonic marginal vein of Servelle was identified in 2 cases. AV shunt was highly suspected in 4 cases and was confirmed by DSA in 1 case, making Klippel-Trénaunay-Weber syndrome a more apt diagnosis. Associated ipsilateral duplicated renal artery was found in 1 case. We have concluded that medical imaging is the cornerstone in the diagnosis and assessment of severity and complications, follow-up and differentiation of KTS from other similar conditions. Different imaging modalities play complementary roles in the evaluation of KTS patients.

Long-term follow-up of fibular graft for the reconstruction of bone defects.

The use of fibular graft for the reconstruction of bone defects has been demonstrated to be a reliable method. The aim of this study was to assess the clinical outcome of graft union, functional outcome (hypertrophy of the graft bones) and complications of both non-vascularized and vascularized grafts.From 1981 to 2015, 10 patients were treated using non-vascularized fibular graft or free vascularized fibular graft. The outcomes were bony union time, graft hypertrophy and complications based on radiograph and functional outcomes according to the Musculoskeletal Tumor Society (MSTS) score. Mobility of the ankle at the donor site was evaluated using the Kofoed ankle score system.This study included 10 patients with an average follow-up of 6.8 years. The union rate for all patients was 100%. The mean union time was 21.3 weeks for vascularized fibular grafts and 30.5 weeks for non-vascularized fibular grafts (P = .310). There was a significant difference between the upper limbs and the lower limbs regarding hypertrophy of the grafts in 5 patients (P = .003). The mean MSTS score in 10 patients was 84% (range 53%–97%). Stress fracture of the graft occurred in 1 patient. Donor site complications, including valgus deformity and length discrepancy, between 2 legs occurred in 2 patients who were under 18 years of age at the time of operation (P = .114). The mean Kofoed score was 96.8 (range 88–100).A greater increase in hypertrophy of grafts was observed with reconstruction in the lower limbs. There was no difference in MSTS score between these 2 types of grafts. Children were more likely to experience the valgus deformity at the donor site after harvesting the fibula. Keeping at least the distal 1/4 of the fibula intact during the surgery is a valid means of ensuring ankle stability at the donor site, and children should be considered for prophylactic distal tibiofibular synostosis creation to prevent the valgus deformity of the ankle at the donor site.

Chemotherapy Curtails Bone Formation From Compliant Compression Fixation of Distal Femoral Endoprostheses.

Modulated compliant compressive forces may contribute to durable fixation of implant stems in patients with cancer who undergo endoprosthetic reconstruction after tumor resection. Chemotherapy effects on bone hypertrophy and osteointegration have rarely been studied, and no accepted radiologic method exists to evaluate compression-associated hypertrophy. (1) What was the effect of chemotherapy on the newly formed bone geometry (area) at 1 year and the presumed osteointegration? (2) What clinical factors were associated with the degree of hypertrophy? (3) Did the amount of bone formation correlate with implant fixation durability? (4) Was the amount of new bone generation or chemotherapy administration correlated with Musculoskeletal Tumor Society (MSTS) score? Between 1999 and 2013, we performed 245 distal femoral reconstructions for primary or revision oncologic indications. We evaluated 105 patients who received this implant. Ten were excluded because they lacked 2 years of followup and two were lost to followup, leaving 93 patients for review. All underwent distal femur reconstruction with the compliant compressive fixation prosthesis; 49 received postoperative chemotherapy and 44 did not. During this period, the implant was used for oncology patients < 60 years of age without metastases and with > 8 cm of intact, nonirradiated bone distal to the lesser trochanter and ≥ 2.5 mm of cortex. Our cohort included patients with painful loosening of cemented or uncemented stemmed femoral megaprostheses when revision with the compliant compressive device was feasible. Patients with high-grade sarcomas all received chemotherapy, per active Children's Oncology Group protocols, for their tumor diagnosis. At each imaging time point (3, 6, 9, 12, 18, 24 months), we measured the radiographic area of the bone under compression using National Institutes of Health open-access software, any shortening of the spindle-anchor plug segment distance as reflected by the exposed traction bar length, and prosthesis survivorship. Clinical and functional status and MSTS scores were recorded at each followup visit. Duration of prosthesis retention without aseptic loosening or mechanical failure was evaluated using Kaplan-Meier analysis, censoring patients at last followup. Chemotherapy was associated with the amount of overall bone formation in a time-dependent fashion. In the 12 months after surgery there was more bone formation in patients who did not receive postoperative chemotherapy than those who did (60.2 mm, confidence interval [CI] 49.3-71.1 versus 39.1, CI 33.3-44.9; p = 0.001). Chemotherapy was not associated with prosthesis survival. Ten-year implant survival was 85% with chemotherapy and 88% without chemotherapy (p = 0.74). With the number of patients we had, we did not identify any clinical factors that were associated with the amount (area) of hypertrophy. The hypertrophied area was not associated with the durability of implant fixation. MSTS scores were lower in patients treated with chemotherapy (25 versus 28; p = 0.023), but were not correlated with new bone formation. The relationships among chemotherapy, bone formation, and prosthetic survivorship are complex. Because bone formation is less in the first year when the patient is being treated with chemotherapy, it is not clear if the rehabilitation schedule should be different for those patients receiving chemotherapy compared with those who do not. The relationship between early bone formation and the timing of weightbearing rehabilitation should be evaluated in a multicenter study. Level III, therapeutic study.

Hypertrophic osteoarthropathy: Case report and literature review

Hypertrophic osteoarthropathy manifests as digital clubbing, subperiosteal new bone formation in tubular bone and diffuse skin hypertrophy. It could be either primary or secondary. We report a 31-year-old man presenting with digital clubbing and diffuse skin thickening which started at puberty. X-rays showed subperiosteal new bone formation. All examinations for secondary causes were negative.

Which plate results in better stability after segmental mandibular resection and fibula free flap reconstruction? Biomechanical analysis

This study investigated the biomechanical stability of 2 plate systems-mini-plates and reconstruction plates-in reconstruction with fibular free flaps. The reconstruction models were constructed by using 2 types of plates in representative cases with segmental mandibular defect (C, L, LC1, LC2). In each model, a masticatory simulation approximating 3 clenching tasks was conducted, using the muscle forces adjusted to the mandible structure used in this study. In addition, to evaluate the sensitivity of the 2 plate systems for masticatory load changes, a sensitivity analysis was also performed by using finite element analysis. The risks of plate fracture and screw loosening measured by stress concentrations were higher in the cases using mini-plates compared with those using reconstruction plates. Moreover, the mini-plate was more sensitive to varied loads compared with the reconstruction plate and was observed to have less flexibility to absorb external forces. Mini-plates also caused high strain values, indicating the risk of hypertrophy of bone around the screw holes. The use of a reconstruction plate should result in more stable surgical outcomes in most cases, but we noted that the risk of atrophy may increase with the use of reconstruction plates because of lack of bone stimulation.

Tibial Tubercle Osteotomy in Total Knee Arthroplasty: Midterm Results Experience of a Monocentric Study.

Purpose Difficult primary total knee arthroplasty (TKA) and revision TKA may be high demanding, especially during joint exposure. Aim of this article is to evaluate the clinical and radiological outcomes of a series of patients, who underwent TKA and revision TKA, where tibial tubercle osteotomy (TTO) was performed. Methods We retrospectively reviewed a cohort of 79 consecutives TKAs where TTO was performed. Patients were assessed clinically and radiographically at their last follow-up (mean, 7.4 ± 3.7 years). Clinical evaluation included the Knee Society Score (KSS), the pain visual analogue scale (VAS), and range of motion. Radiological assessment included the evaluation of radiolucent lines, osteolysis, cortical bone hypertrophy, time of bone healing of the TTO fragment, and the hardware complication. Results KSS raised from 40.7 ± 3.1 to 75 ± 4.3 ( p < 0.0001). Knee flexion increased from 78.7 ± 9.9° to 95.0 ± 9.5° ( p < 0.0001), and VAS improved from 7.9 ± 0.9 to 3.8 ± 1 ( p < 0.0001). No signs of loosening or evolutive radiolucency lines were found. Osteolytic areas around the stem were detected. No significant association was found between the implant design and the outcomes, while aseptic loosening showed significantly better results. Complications were: 4 painful hardware, 3 late periprosthetic infections, 1 extension lag of 5°, and 3 flexion lag. Conclusion Our experience suggests the use of TTO to improve the surgical approach in difficult primary TKA or revision TKA. A precise surgical technique leads to good results with low risk of complications. Level of Evidence Level IV, therapeutic case series.

Arthroscopic decompression of extra-articular subspinal hip impingement

Complete arthroscopic decompression of the impinging subspinal soft tissues and resection of the hypertrophic bone formation between the anterior hip capsule and the anterior inferior iliac spine (AIIS) or decompression of ahypertrophic AIIS. Painful anterior hip impingement and decreased hip flexion following ahypertrophic osseous subspinal deformation. No clinical symptoms or decreased anterior hip function despite radiological osseous subspinal hip impingement. Hip arthroscopy in supine position on an extension table. Treatment of possible intraarticular hip pathologies in the central or peripheral compartment. Arthroscopic visualization of the hypertrophic impinging soft tissues below the AIIS and decompression using ashaver or radiofrequency device. Complete arthroscopic resection of the hypertrophic AIIS parts and the osseous subspinal deformation using ahigh speed burr under fluoroscopic control. Early functional rehabilitation with full weight-bearing and unlimited hip motion; 3weeks ossification prophylaxis and 8weeks of limitation for jumping and running sports activities. There are no comparative studies or medium- and long-term study results in the literature for arthroscopic AIIS decompression. However, currently published case series show an improvement of the determined scores.

Arthroscopic Treatment of Osteochondral Lesions of the Talus Using Juvenile Articular Cartilage Allograft and Autologous Bone Marrow Aspirate Concentration

Juvenile allogenic chondrocyte implantation (JACI; DeNovo NT Natural Tissue Graft®; Zimmer, Warsaw, IN) with autologous bone marrow aspirate concentrate (BMAC) is a relatively new all-arthroscopic procedure for treating critical-size osteochondral lesions (OCLs) of the talus. Few studies have investigated the clinical and radiographic outcomes of this procedure. We collected the clinical and radiographic outcomes of patients who had undergone JACI-BMAC for talar OCLs to assess treatment efficacy and cartilage repair tissue quality using magnetic resonance imaging (MRI). Forty-six patients with critical-size OCLs (≥6 mm widest diameter) received JACI-BMAC from 2012 to 2014. We performed a retrospective medical record review and assessed the functional outcomes pre- and postoperatively using the Foot and Ankle Outcome Score (FAOS) and Short-Form 12-item general health questionnaire. MRI was performed preoperatively and at 12 and 24 months postoperatively. Cartilage morphology was evaluated on postoperative MRI scans using the magnetic resonance observation of cartilage tissue (MOCART) score. The pre- to postoperative changes and relationships between outcomes and lesion size, bone grafting, lesion location, instability, hypertrophy, and MOCART scores were analyzed. Overall, the mean questionnaire scores improved significantly, with almost every FAOS subscale showing significant improvement postoperatively. Concurrent instability resulted in more changes that were statistically significant. The use of bone grafting and the presence of hypertrophy did not result in statistically significant changes in the outcomes. Factors associated with outcomes were lesion size and hypertrophy. Increasing lesion size was associated with decreased FAOS quality of life subscale and hypertrophy correlating with changes in the pain subscale. Of the 46 patients, 22 had undergone postoperative MRI scans that were scored. The average MOCART score was 46.8. Most patients demonstrated a persistent bone marrow edema pattern and hypertrophy of the reparative cartilage. Juvenile articular cartilage implantation of the DeNovo NT allograft and BMAC resulted in improved functional outcome scores; however, the reparative tissue still exhibited fibrocartilage composition radiographically. Further studies are needed to investigate the long-term outcomes and determine the superiority of the arthroscopic DeNovo procedure compared with microfracture and other cartilage resurfacing procedures.

Muscular Dystrophy during Osteoarthritic Disorder: A Novel Diagnostic Protocol Evidenced by Biochemical and Anatomical Parameters

Background: Muscular Dystrophy during Osteoarthritic Disorder (MD-OAD) is a group of disorders characterized by muscle wasting, weakness and degeneration along with potential loss of joint cartilage, bone hypertrophy, painful Joint effusion and restricted movement of joints. Creatine Kinase-Muscle (CK-MM) and AldolaseA (AldoA) are considered to be realistic biomarkers to detect the MD-OAD. The aim of the study was to evaluate the serum levels of CK-MM and AldoA and determine their correlation with risk factors such as muscle weakness, muscle degeneration, skeletal muscle damage resulting in deranged anatomical features developed in MD-OAD.

Manifestações musculoesqueléticas na síndrome de Klippel-Trenaunay

Klippel-Trenaunay syndrome is a rare congenital disease with undefined etiology characterized by the presence of the triad: port wine stains, venous malformations or varicose veins, and bone and/or tissue hypertrophy. It affects the lower limbs more commonly. Treatment is generally conservative, with interventions limited to the treatment of complications. Objective: To present a case report of a child with musculoskeletal manifestations of the syndrome evaluated by a multiprofessional team, composed of social work, psychology, physiotherapy, occupational therapy, phonoaudiology, nursing and a physiatrist. Methods: After evaluation, it was decided that awareness and correction of posture as well as body perception, performance of orthostatic activity, balance training, dissociation of waists, and postural changes would be approached by the multiprofessional team. Results: The patient received multiprofessional care for two months, obtained better gait stability, and had independent gait in the community, with higher speed and lower number of falls. Conclusion: She was discharged after achieving the goals and after her parents were sensitized regarding the importance of maintaining the multiprofessional follow up and follow the goals set for homecare.

Combined capillary-venous-lymphatic malformations without overgrowth in patients with Klippel-Trénaunay syndrome.

Klippel-Trénaunay syndrome (KTS) is described in the literature as a complex syndrome characterized by various combinations of capillary, venous, and lymphatic malformations associated with limb overgrowth. In the first description by Maurice Klippel and Paul Trénaunay, tridimensional bone hypertrophy was believed to be the cause of limb enlargement. The purpose of this study was primarily to assess the presence of real bone hypertrophy as a cause of enlargement of the limb and to underline the rare presence of undergrowth of the affected limb in patients with KTS. A two-center retrospective review including 17 KTS patients with various combinations of capillary, venous, and lymphatic malformation affecting the lower limb was performed. Differences in limb dimension were evaluated clinically. Width and length discrepancy of the affected limb was measured with radiologic imaging. We found an increase of length in the affected limb in 80% of the patients. The leg length discrepancy varied from 0.2 to 2.6cm. The median leg length discrepancy was found to be 1.4cm. Three patients had a reduced length of the affected limb. Girth enlargement of the affected extremity was noticed in 60% of the patients, and 2 of 17 patients had hypotrophy of the involved limb. Hypertrophy (an increase in both length and width) of the bone was found in none of our cases, and the circumferential enlargement of the affected extremity was related only to soft tissue enlargement. In the literature, KTS is considered the prototype of overgrowth syndromes associated with complex vascular malformations. The majority of our patients showed limb length increase associated with soft tissue enlargement without an increase of bone width; there were also two patients with limb undergrowth. A real bone overgrowth (an increase in both length and width) was not present in our patients. Therefore, we could consider the absence of real bone hypertrophy as probably a new aspect of such confusing and controversial definitions of KTS. In addition, it would be more accurate to classify KTS patients on the basis of their phenotypic features (type of vascular malformation, types of overgrown tissue) rather than by use of an outdated eponym.

Intraoperative delivery of the Notch ligand Jagged-1 regenerates appendicular and craniofacial bone defects

Each year, 33% of US citizens suffer from a musculoskeletal condition that requires medical intervention, with direct medical costs approaching $1 trillion USD per year. Despite the ubiquity of skeletal dysfunction, there are currently limited safe and efficacious bone growth factors in clinical use. Notch is a cell–cell communication pathway that regulates self-renewal and differentiation within the mesenchymal/osteoblast lineage. The principal Notch ligand in bone, Jagged-1, is a potent osteoinductive protein that positively regulates post-traumatic bone healing in animals. This report describes the temporal regulation of Notch during intramembranous bone formation using marrow ablation as a model system and demonstrates decreased bone formation following disruption of Jagged-1 in mesenchymal progenitor cells. Notch gain-of-function using recombinant Jagged-1 protein on collagen scaffolds promotes healing of craniofacial (calvarial) and appendicular (femoral) surgical defects in both mice and rats. Localized delivery of Jagged-1 promotes bone apposition and defect healing, while avoiding the diffuse bone hypertrophy characteristic of the clinically problematic bone morphogenetic proteins. It is concluded that Jagged-1 is a bone-anabolic agent with therapeutic potential for regenerating traumatic or congenital bone defects.

Magnetic resonance imaging manifestations of deep vascular diseases in children with superficial vascular diseases

Objective To assess the clinical value of magnetic resonance imaging (MRI) in the diagnosis of deep vascular diseases in children with superficial vascular diseases. Methods From January 2012 to December 2016, 105 children with superficial vascular diseases in the Department of Dermatology of Shanghai Children′s Hospital underwent MRI examination, and the clinical and imaging data were analyzed. Results Of the 105 children, 42 were male and 63 were female. Their ages ranged from 0.5 to 168 months with an average age of 21.6 months. As MRI showed, 25 (23.8%) children had deep vascular diseases, which could not be seen with naked eyes. These deep vascular diseases included multisite deep capillary hemangiomas in 15 cases, cranial-facial hemangioma syndrome in 4, arteriovenous malformation in 3, persistent intracranial artery sinus in 2, and varicosity and bone hypertrophy syndrome in 1. Conclusion MRI is of great value to the diagnosis of deep vascular diseases in children with superficial vascular diseases. Key words: Hemangioma; Magnetic resonance imaging; Vascular malformations

Cryopyrinopathies

Cryopyrin-associated periodic syndromes (CAPS) are linked to one single gene mutations, however they are associated with 3 syndromes, which are, from the mildest to the most severe phenotype familial cold urticaria, Muckle-Wells syndrome and chronic, infantile, neurologic, cutaneous, articular (CINCA) syndrome also called neonatal-onset multisystem inflammatory disease (NOMID). Autosomic dominant inheritance is present in most cases but in CINCA/NOMID syndrome where neomutations are more common. Mutations in the gene encoding cryopyrin, NLRP3, are associated with deregulation of caspase-1 activity, excessive interleukin-1 production and an autoinflammatory syndrome, which in familial cold urticaria and Muckle-Wells syndrome may be triggered or worsened by exposure to coldness. More and more mutations are described and even somatic mutations that can explain some clinical signs beginning in adulthood. Patients disclose a pseudo-urticarial rash, arthralgia, headaches, sometimes fever, biological inflammation but also, in severe forms of the disease, neurologic inflammation with central deafness, ophthalmologic inflammation, chronic meningitis. Some CINCA/NOMID patients also develop growth cartilage pseudo-tumoral hypertrophy. Natural disease history is usually benign in familial cold urticarial but severe in the other forms, particularly regarding neuro-sensorial involvement. In addition, secondary AA amyloidosis may develop in all forms in the absence of control of chronic inflammation. Anti-interleukin-1 treatment with anakinra, rilonacept or canakinumab induces in most cases complete remission, however sequelae may be present, particularly if central deafness or cartilage bone hypertrophy have already developed. This treatment is also important to prevent secondary amyloidosis or stabilize and even sometimes allow improvement of amyloidosis lesions.