Lower Limb Deformities Research Articles

An Unusual Case of a Conus Hanging by a Thread.

ABSTRACTWe report a rare cause of paraparesis in a 2-year-old girl. Along with lower limb weakness, she presented with a neurogenic bladder and lower limb deformities. Her magnetic resonance imaging showed multiple dorsolumbar segmentation defects and a dysgenetic spinal cord segment between T10 and S1. A thin septum connected the lower end of the normal cord to a bulky conus at S1-2. These features were suggestive of type 1 segmental spinal dysgenesis. The findings were confirmed at surgery, and the child was referred for supportive care.

Adult Traumatic Eight Days Old Anterior Dislocation of the Hip with Ipsilateral Fracture Upper Third Shaft Femur: An Atypical Case Report

Introduction: Anterior or posterior dislocation of hip are usually associated with fracture head of femur but dislocations associated with femoral neck, trochanter and shaft are very rare and among this anterior dislocation of hip with ipsilateral fracture of shaft femur is an extremely rare injury. We reported a case of anterior dislocation of hip associated with ipsilateral fracture shaft femur upper third in adult male. Case presentation: A 25 yrs male, low socioeconomic status was brought to our emergency department was conscious but unable to mobilize his right lower limb and external rotation deformity was present with some shortening. No neurovascular compromise and was found fracture shaft femur along with anterior dislocation of right hip on x-ray and treated by close reduction of femoral head and internal fixation of fracture shaft femur by intramedullary nail. Conclusion: Early diagnosis of hip dislocation is essential to prevent avascular necrosis of femur head in future. We concluded that there is no need of open reduction for anterior hip dislocation in every such case. Close reduction of anterior dislocation of hip followed by femur interlocking for femoral shaft fracture is good option for management for such type of injuries. Keywords: Hip dislocation, Close reduction, Avascular necrosis, Fracture dislocation

Short-term comparison of the use of static and expandable intramedullary rods in the lower limbs of children with osteogenesis imperfecta

ABSTRACT BACKGROUND: Children with osteogenesis imperfecta suffer from frequent fractures and deformities due to skeletal fragility. Stabilisation of fractures, correction of deformity and intramedullary rodding result in decreased pain and improved function. Modern expandable intramedullary rods aim to provide lasting stability during growth, without an increase in complications. The aim of our study was to determine and compare the outcome of static Rush rods and expandable Fassier-Duval rods in terms of complications and reoperation rate. METHODS: We reviewed the records of a cohort of 17 children (seven female) with osteogenesis imperfecta (11 Sillence type III, six Sillence type IV) who were treated with intramedullary rods in the lower limb between 2011 and 2017. They had 64 rodding (38 femoral and 26 tibial) procedures (26 Rush rods and 38 Fassier-Duval rods). These were a primary procedure in 46, and a revision procedure after previous Rush rodding in 18 cases. RESULTS: The overall complication rate was 66% (n=42). There was a higher complication rate in the Rush rod group (81%, n=21) when compared to the Fassier-Duval group (55%, n=21)(p=0.035). The most frequent complication in the Rush rod group was distal deformity as the rod is outgrown (69%, n=18). The most frequent complication in the Fassier-Duval rod group was intramedullary migration due to a failure to expand (45%, n=17). Factors that were associated with increased risk of complications included younger age (p=0.031), type of rod (p=0.035), and deformity as an indication for surgery (77% complications, p=0.033). At a mean follow-up of 3.1 years, the reoperation rate in the Rush rod group was 58% (n=15). Comparatively, at a mean of 3.7 years follow-up, there were no reoperations in the Fassier-Duval group. CONCLUSIONS: Despite the numerous innovations, the surgical management of lower limb deformities and fractures in children with osteogenesis imperfecta remains challenging with a relatively high complication rate. The use of Fassier-Duval rods may result in a lower reoperation rate when compared to Rush rods, in the short term. Level of evidence: Level 4 Keywords: osteogenesis imperfecta, intramedullary rod, Rush rod, Fassier-Duval rod, fracture, deformity

Surgical treatment for permanent dislocation of patella after correction for lower limb deformity due to Ollier’s disease :a case report

Surgical treatment for permanent dislocation of patella after correction for lower limb deformity due to Ollier’s disease :a case report

Deformity correction with the ifixation system: A new era of six-axis correction frames

The technology of computer-assisted six-axis frames is rapidly evolving. In this case report, we describe two cases of pediatric lower limb deformities treated by a novel hexapod device, the iFIXation system. For our knowledge, this is the first report in literature for its usage. The first case was a 14-years-old girl with posttraumatic shortening, varus and external rotation deformities of her lower limb around the ankle. All the deformities and shortening were corrected simultaneously with the iFIXation system. The second case was an 8-years-old girl with postinfection valgus and external rotation of the knee as well as shortening of the femur. Distal femoral deformities and shortening were simultaneously corrected by the iFIXation system and growth modulation to prevent recurrence of the deformity was done. The reported cases represent our earliest experience with the iFIXation system.

Molecular Diagnoses of X-Linked and Other Genetic Hypophosphatemias: Results From a Sponsored Genetic Testing Program.

ABSTRACTX‐linked hypophosphatemia (XLH), a dominant disorder caused by pathogenic variants in the PHEX gene, affects both sexes of all ages and results in elevated serum fibroblast growth factor 23 (FGF23) and below‐normal serum phosphate. In XLH, rickets, osteomalacia, short stature, and lower limb deformity may be present with muscle pain and/or weakness/fatigue, bone pain, joint pain/stiffness, hearing difficulty, enthesopathy, osteoarthritis, and dental abscesses. Invitae and Ultragenyx collaborated to provide a no‐charge sponsored testing program using a 13‐gene next‐generation sequencing panel to confirm clinical XLH or aid diagnosis of suspected XLH/other genetic hypophosphatemia. Individuals aged ≥6 months with clinical XLH or suspected genetic hypophosphatemia were eligible. Of 831 unrelated individuals tested between February 2019 and June 2020 in this cross‐sectional study, 519 (62.5%) individuals had a pathogenic or likely pathogenic variant in PHEX (PHEX‐positive). Among the 312 PHEX‐negative individuals, 38 received molecular diagnoses in other genes, including ALPL, CYP27B1, ENPP1, and FGF23; the remaining 274 did not have a molecular diagnosis. Among 319 patients with a provider‐reported clinical diagnosis of XLH, 88.7% (n = 283) had a reportable PHEX variant; 81.5% (n = 260) were PHEX‐positive. The most common variant among PHEX‐positive individuals was an allele with both the gain of exons 13–15 and c.*231A>G (3′UTR variant) (n = 66/519). Importantly, over 80% of copy number variants would have been missed by traditional microarray analysis. A positive molecular diagnosis in 41 probands (4.9%; 29 PHEX positive, 12 non‐PHEX positive) resulted in at least one family member receiving family testing. Additional clinical or family member information resulted in variant(s) of uncertain significance (VUS) reclassification to pathogenic/likely pathogenic (P/LP) in 48 individuals, highlighting the importance of segregation and clinical data. In one of the largest XLH genetic studies to date, 65 novel PHEX variants were identified and a high XLH diagnostic yield demonstrated broad insight into the genetic basis of XLH. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Complex foot deformities associated with lower limb deformities: a new therapeutic strategy for simultaneous correction using Ilizarov procedure together with osteotomy and soft tissue release

AimThe aim of the current study is to introduce a new therapeutic strategy for simultaneous correction of complex foot deformities (CFD) and the associated lower limb deformities (LLD) by using Ilizarov technique with osteotomy and soft tissue procedure and to report its early clinical results.MethodsA retrospective review of CFD associated with LLD simultaneous correction utilizing the Ilizarov procedure together with osteotomy and soft tissue balance from 2015 to 2019 was conducted.ResultsThirty-two patients were followed for an average of 42.8 months. The mean external fixation time (EFT) was 6.5 months. The mean healing index (HI) was 1.7 months/cm. At the time of fixator removal, plantigrade feet were achieved in all patient and lower limb deformities were corrected. No recurrence of the deformities occurred. The mean LLRS AIM score was improved from 7.5 to 0.3. At the final follow-up, the ASAMI-Paley score was graded as excellent in all limbs in the aspect of bone results, and functional results were defined as excellent in 29 (90.6%) limbs and good in 3 (9.4%) limbs. The mean modified Dimeglio score was significantly improved from 7.2 to 1.3. No deep infection of the osteotomy site or nonunion was noted in the current study.ConclusionThe therapeutic strategy by using the Ilizarov procedure together with osteotomy and soft tissue balance is a safe and effective way to simultaneously correct CFD and LLD.Level of evidenceLevel IV, retrospective case series

Can the TrueLok Hexapod System™ be used to accurately correct lower limb deformity in children?

IntroductionProgressive bone lengthening in children can be done using an external fixator, a lengthening nail, or plate with screws. The TrueLok Hexapod System™ (TL-HEX™) is the newest hexapod external fixator on the market. We hypothesized that the TL-HEX™ can accurately correct lower limb deformities in children. The goal of this study was to evaluate the clinical and radiographic outcomes after correcting lower limb deformities in children using the TL-HEX™ system. Material and methodsData from 58 limbs that underwent bone lengthening with the TL-HEX™ were analyzed for this retrospective, single-center study. The average patient age was 11.4 years. The femur was lengthened in 23 limbs and the tibia in 35. The outcomes were evaluated using long leg standing radiographs preoperatively and at the final assessment. The variables of interest were the mechanical axis deviation (MAD), mechanical lateral distal femoral angle (mLDFA), mechanical lateral proximal tibia angle (mMPTA), healing index (HI) and accuracy of the correction. The complications were graded on a 4-point scale summarizing three broad goals: planned correction, duration of treatment and sequelae. The accuracy of the correction was defined as the difference between the planned correction and the actual correction achieved. ResultsThe mean HI was 37 days/cm. Significant correction was achieved for leg length discrepancy (LLD) (60 mm vs. 20 mm; p<0.01) and mLDFA (88.6° vs. 89.9°; p=0.04) but not the MAD (17.7 vs. 14.7; p= 0.17) or mMPTA (87.3 vs. 88.1; p=0.08). In the entire cohort, the difference from planned was 12.5 mm (p<0.01) for lengthening, 1.3° for the mLDFA (p=0.5) and 3° for the mMPTA (p=0.02). Relative to the initial goal, the mean lengthening achieved was 118%. In the sub-group where the plan did not need to be modified, the accuracy of the correction was better. There were 40 complications (69%). ConclusionThe TL-HEX™ is an effective and accurate system. The complication rate associated with its use is the same as other hexapod external fixators. Surgeons and patients must be aware of the high complication rate, which may require the plan to be modified and could potentially compromise the outcome.

Design and Analysis of Foot Orthotic For Lower Limb Deformities Using Composites

This research details a procedure for the systematic design of foot orthotics based on simulation models and validation of the same with subsequent experiment. The present model may ultimately to replace the use of empirical tables for the designing of foot orthotics in accordance to the weight and activities of end-users. This present model is so general that it can simulate different kind of orthotics, loading conditions and material properties to give the desired output. Finally, the proposed model and the corresponding results may lead to the form of design basis for new generation foot orthotics. The methodical approach to the development of engineering analysis models using the FEA technique. Orthotic devices have been commonly made from plastics like polypropylene. However, insufficient mechanical properties, labour intensive preparation process, long client’s visiting times urge us to seek an alternative. Presently, two different advanced composite materials (Glassfiber, Basalt-fiber) have been chosen for the analysis purpose to achieve the low weight and High Strength.

Rachitismo ipofosforemico X-linked

X-linked hypophosphatemia (XLH) is an X-linked disorder with dominant penetration, caused by mutations in the PHEX gene, which encodes for an endopeptidase that is predominantly expressed in osteoblasts, osteocytes and odontoblasts. PHEX mutations cause increased production of fibroblast growth factor 23 (FGF23) that in turn leads to hypophosphatemia by causing inhibition of the renal phosphate reabsorption and of the synthesis of active 1,25-dihydroxyvitamin D. In children XLH is characterised by rickets, bone pain, physical dysfunction, impaired growth, disproportionate short stature, lowerlimb deformities, pathological fractures, dental malposition and dental abscesses. Although phenotype may be variable in severity, early diagnosis and treatment are critical to improve outcome. Laboratory tests show hypophosphatemia associated with hyperphosphaturia and elevated alkaline phosphatase, while parathormone and calcium levels are normal. For decades, patients have been treated with conventional therapy, including active vitamin D supplementation and fractionated daily doses of oral phosphate salts. However, these therapies rarely normalise the phenotype. More recently, burosumab, a recombinant human IgG1 monoclonal antibody against FGF-23, has been introduced for the treatment of XLH. In phase 2 trials, burosumab has been shown to improve significantly clinical symptoms, as well as biological and radiological signs of rickets.

A case report of severe degenerative lumbar scoliosis associated with windswept lower limb deformity

BackgroundThe windswept lower limb deformity describes valgus deformity in one leg with varus deformity in the other. It is mostly seen in young children with metabolic bone diseases (such as rickets) and may lead to leg length discrepancy (LLD) and Degenerative scoliosis (DS) in older age. To the best of our knowledge, there was no report of the spinal surgery in patient with severe DS associated with windswept deformity. The objective of this study is to report the unique case of a 60-year-old woman with severe degenerative scoliosis (DS) associated with windswept deformity caused by rickets who underwent a posterior correction and fusion surgery in spine.Case presentationThe patient was diagnosed as rickets windswept lower limb deformity for 50 years but never went through routine treatment. Then, she performed lumbar scoliosis for more than 20 years and suffered from severe back pain for 4 years. After overall clinical evaluation and radiographic measures, we performed a posterior surgical correction and fusion from T9-L5. With this surgery, the main thoracolumbar curve Cobb angle corrected from 72.5° to 21.0°, the coronal balance from 0 cm to 2.0 cm while the sagittal vertical axis (SVA) from 1.5 cm to − 1.0 cm. At 2 years postoperative follow-up, her back pain has almost completely relieved with a satisfied fixation and bone fusion showed on CT scans. However, a coronal imbalance was found with C7-CSVLdistance equal to 4.0 cm. This coronal imbalance was highly correlated to the untreated LLD and pelvic obliquity, and should be improved by standing posture or shoe lifts.ConclusionsFor such patient, the pure spinal correction and fusion surgery, in spite of lower limbs deformity, can achieve good relieve of back pain symptom, however may accompany by the complication of coronal imbalance due to the unimproved pelvic obliquity and LLD. However, longer follow-up is necessary to observe the long-term outcome of this patient’s postoperative coronal imbalance.

Schwartz–Jampel syndrome: comprehensive diagnostics and orthopedic treatment

Schwartz–Jampel syndrome (chondrodystrophic myotonia) is a monogenic genetic disorder, demonstrating unique coincidence of the features of skeletal dysplasia and neuromuscular disease. We present four clinical cases of Schwartz–Jampel syndrome. Principles of diagnostic and results of surgical treatment of the lower limbs deformities are discussed. Importance of this study comprises unique description of rare cases. Surgical treatment for orthopaedic conditions is important and can lead to functional improvement, prevent progression of deformities and enhance daily activity.

EFFECTIVENESS OF TENDON-MUSCLE PLASTY OF THE KNEE JOINT IN PATIENTS HAVING SPASTIC CEREBRAL PALSY WITH FLEXION CONTRACTURES OF KNEE JOINTS

Introduction. Cerebral palsy (CP) is the main cause of childhood neurological disability in the world. Due to the fact that the prevalence of knee contractures in children with cerebral palsy occupies the 3rd place in the structure of orthopedic pathology of the lower extremities, this topic is least covered in the scientific periodicals. Material and methods. Findings from 40 patients of the main group, aged 7-12 and having cerebral palsy (CP), were studied retrospectively. They had knee flexion contractures with patella alta. Findings of goniometry and of Gillette FAQ were analyzed before and after surgery. The Spearman coefficient was used for the correlation analysis of goniometry parameters and surgical intervention effectiveness before surgery. 35 patients having no bilateral CP damage and other diseases leading to lower limb deformities were included into the reference group. X-ray examination and goniometry assessment of a healthy limb were made in patient’s lying position on his back with passive extension; plus goniometry in a standing position with shin active extension. Results. The median of deformation angles before and after surgery was 20° and 5°, respectively (p

Axial and rotational alignment of lower limb in a Caucasian aged non-arthritic cohort

BackgroundThe alignment of human lower limb has been an area of ongoing study for decades. The purpose of this study was to analyze the axial and rotational alignment from hip to ankle in a Caucasian aged non-arthritic cohort.MethodsA non-arthritic cohort of aged patients was retrospectively analyzed by computer tomography. Anatomical–mechanical angle of femur (AMA), femur inclination (FI), femoral anteversion (FA), posterior condylar angle (PCA), proximal tibial torsion (TEAs-PTC and TEAs-PTT) and tibial fibular torsion (PTC-TFA) were measured.ResultsThe median age of the patients was 76 years (range 67 to 91 years). Regarding axial alignment, the AMA was 5 (2.94; 6.80). No significance differences were reported by side and age. AMA was significantly lower in men. The FI was 125.3 (120.0; 134.8) with no differences in terms of side, age or gender. Regarding torsion alignment, the median values of FA, PTC-TFA and TEAs-PTT were, respectively, 16.8, 28.5 and − 1.4. No differences were reported by age. Right tibia was externally rotated by 1.5 degrees as compared to the left side (P 0.035).ConclusionThe broad variability of the parameters analyzed highlights the necessity for a more anatomical and individualized approach during surgery of lower limb. The present study offers the fundament to understand and treat lower limb deformities. Hence, these data can constitute the normal reference values useful to investigate lower limb malalignment. Moreover, it helps to assess the possible changes of axial and rotational alignment in idiopathic OA of lower limb.Level of evidence IIIRetrospective cohort study

Inter-relationship between footprints and photogrammetry

Introduction: Alterations in foot landing position have often been associated with the appearance of deformities in lower limbs. However, there are no studies that prove the relationship between these two variables in healthy individuals. Objective: To investigate the relation between changes in feet and lower limbs by plantigraphy and computerized photogrammetry. Methods: The study included 70 young adults, 42 women (height: 1.60±0.01 m; body weight: 58.0±0.92 kg; body mass index: 22.0±0.31 kg/m2 ) and 28 men (height: 1.70±0.01 m; body weight: 70.0±1.4 kg; body mass index: 23.0±0.42 kg/m2 ) with mean age of 21.62±2.0 and 22.18±2.09 years, respectively. Plantigraphy of both feet and photographic capture in the anterior frontal plane of lower limbs and foot, posterior frontal of the tendon of the calcaneus and in the sagittal plane of lower limbs were performed. Results: A strong positive correlation was observed between the Chippaux-Smirak and the Staheli indexes (Men– r: 0.863 and p&lt;0.001; Women– r: 0.973 and p&lt;0.001) and a weak positive correlation between the malleolar angle and the Cavanagh-Rodgers index (Men– r: 0.386 and p 0.003; Women– r: 0.280 and p 0.010). Conclusion: There was no correlation between footprint indexes and lower limb angles measured by computerized photogrammetry.

Disease-specific gait deviations in pediatric patients with X-linked hypophosphatemia

BackgroundX-linked hypophosphatemia (XLH) represents the most common genetic form of rickets featuring profound hypophosphatemia with associated skeletal and non-skeletal manifestations. Early onset gait disturbances contribute strongly to the burden of disease. However, no study has comprehensively characterized naturally occurring gait deviations in pediatric patients with XLH. Research questionsCan disease-specific gait deviations and potentially influencing factors be identified by gait analysis in non-surgically treated children with XLH? MethodsGait laboratory assessments of 12 pediatric patients with XLH without previous long bone surgery was retrospectively analyzed and compared to age-matched healthy controls. Radiologic and clinical parameters of XLH patients were correlated with kinematic gait variables and gait scores. ResultsReduced external knee rotation and increased external hip orientation was ubiquitous in children with XLH. Increased lateral trunk lean, or “waddling gait”, occurred in five children and was associated with varus knee deformities. Overall, children with XLH showed a reduced Gait Deviation Index (GDI) compared to controls. Radiologic and gait analysis revealed complex combined frontal and torsional deformity of the lower limbs as a common feature in XLH. Higher Body Mass Index (BMI) was associated with both lateral trunk lean and impaired GDI. SignificanceGait analysis is feasible to quantify gait deviations and lower limb deformities in pediatric patients with XLH. Specific gait characteristics including internal knee rotation and external hip rotation are common among patients with XLH and contribute to impaired gait scores. Our data suggest the use of gait and deformity data assessment as outcome parameters in future observational and interventional studies. Standardized assessment might contribute to targeted treatments to improve life quality in XLH patients.

A Simple External Fixator Construct for Assessment of Intra-operative Hip-Knee-Ankle Axis Alignment in Lower Limb Deformity Correction Surgery.

A Simple External Fixator Construct for Assessment of Intra-operative Hip-Knee-Ankle Axis Alignment in Lower Limb Deformity Correction Surgery.

Biomechanical Study on the Stress Distribution of the Knee Joint After Tibial Fracture Malunion with Residual Varus-Valgus Deformity.

ObjectiveTo investigate the effect of residual varus and valgus deformity on the stress distribution of the knee joint after tibial fracture malunion.MethodsFourteen adult cadaver specimens were selected to establish the models of tibial fractures, which were fixed subsequently at neutral position (anatomical reduction) and malunion positions (at 5°, 10°, and 15° valgus positions, and 5°, 10°, and 15° varus positions). The stress distribution on the medial and lateral plateau of the tibia was quantitatively measured using ultra‐low‐pressure sensitive film technology. The changes in the stress distribution of the knee joint after tibial fracture malunion and the relationship between the stress values and the residual varus or valgus deformity were analyzed.ResultsUnder 400 N vertical load, the stress values on the medial and lateral plateau of the tibia at the neutral position were 1.137 ± 0.139 MPa and 1.041 ± 0.117 MPa, respectively. When compared with the stress values measured at the neutral position, the stress on the medial plateau of the tibia was significantly higher at varus deformities and lower at valgus deformities, and the stress on the lateral plateau was significantly higher at valgus deformities and lower at varus deformities (all P < 0.05). The stress values on the medial plateau of the tibia were significantly higher than the corresponding data on the lateral plateau at neutral and 5°, 10°, and 15° varus deformities, respectively (all P < 0.05), and significantly lower than the corresponding data on the lateral plateau at 5°, 10°, and 15° valgus deformities, respectively (all P < 0.05).ConclusionResidual varus and valgus deformity after tibial fracture malunion can lead to obvious changes of the stress distribution of the knee joint. Therefore, tibial fractures should be reduced anatomically and fixed rigidly to avoid residual varus–valgus deformity and malalignment of lower limbs.

SUN-356 Burosumab Resulted in Greater Clinical Improvements Compared with Higher-dose Conventional Therapy in Children with X-linked Hypophosphatemia (XLH)

In XLH, excess circulating FGF23 causes hypophosphatemia, rickets, lower limb deformity, and impaired growth and mobility. An active-controlled, phase 3 trial (CL301; NCT02915705) showed treatment with burosumab, a fully human monoclonal antibody against FGF23, resulted in significantly greater improvements in all of these outcomes in children with XLH, compared with continuing oral phosphate and active vitamin D as conventional therapy (Pi/D) per established guidelines. In a post-hoc analysis, we compared children who received burosumab vs those who received an average 64-week oral phosphate daily dose >40 mg/kg (higher-dose Pi) vs ≤40 mg/kg (lower-dose Pi). Sixty-one children with XLH (1–12 years-old) were randomized 1:1 after a 7-day Pi/D washout to receive burosumab (n=29) starting at 0.8 mg/kg subcutaneously Q2W or to resume Pi/D (n=32) titrated by their investigator, for 64 weeks. Eligibility criteria included Rickets Severity Score (RSS) ≥2.0 despite prior Pi/D treatment. Of the 32 subjects randomized to Pi/D, 12 received average higher-dose Pi and 20 received average lower-dose Pi (as specified above). The primary endpoint was rickets healing, using the Radiographic Global Impression of Change (RGI-C) Scale. At week 64, the improvement in the least square (LS) mean (LS mean [±SE; 95%CI]) RGI-C Global Score for rickets was greater on burosumab (+2.06 [0.072; 1.92, 2.20]) compared with either higher-dose (+1.02 [0.241; 0.55, 1.50]) or lower-dose (+1.04 [0.162; 0.73, 1.36]) Pi. The mean decrease in the total RSS from baseline was also greater on burosumab (-2.23 [0.117; -2.46, -2.00]) compared with higher-dose (-0.87 [0.264; -1.39, -0.35] or lower-dose (-1.09 [0.180; -1.45, -0.74]) Pi. Similarly, the mean RGI-C Lower Limb Deformity Score was greater on burosumab (+1.25 [0.170; 0.92, 1.59]) compared with either higher-dose (+0.32 [0.188; -0.05, 0.69]) or lower-dose (+0.26 [0.146; -0.02, 0.55]) Pi. Adverse events including hypersensitivity and injection site reactions, were more frequent with burosumab, and were mild to moderate in severity overall. No discontinuations occurred. In conclusion, children with XLH treated with burosumab had greater improvements in rickets and lower limb deformity compared with subjects receiving higher or lower doses of Pi.

SUN-363 Hypophosphatemia Gene Panel Sponsored Program: A High Yield Of Molecular Diagnoses from Clinically Confirmed XLH and Suspected XLH/ Genetic Hypophosphatemia

X-linked hypophosphatemia (XLH), an X-linked dominant disorder caused by a pathogenic change (variant) in the PHEX gene, affects males and females of all ages. Rickets and osteomalacia may be present along with short stature, lower limb deformity, muscle pain and/or weakness/fatigue, bone pain, joint pain/stiffness, hearing difficulty, enthesopathy, osteoarthritis and dental abscesses. Patients with XLH have below-normal serum phosphate and elevated serum FGF23. XLH is one of multiple etiologies of hypophosphatemia; depending on genetic cause, management may differ. The program provides a no-cost test to confirm a clinical XLH diagnosis or to aid diagnosis of suspected XLH or other genetic hypophosphatemia. Methods Program eligibility criteria: >/=1y old and either clinical XLH diagnosis (confirmatory) or suspicion of XLH/ genetic hypophosphatemia (suspected) as evidenced by 2 or more clinical signs/ symptoms. The next generation sequencing gene panel includes 13 genes: ALPL, CLCN5, CYP2R1, CYP27B1, DMP1, ENPP1, FAH, FAM20C, FGF23, FGFR1, PHEX, SLC34A3 and VDR. Copy number variant (CNV) detection was performed. Results 317 unrelated probands have been tested as of October 2, 2019. Of 158 XLH confirmatory samples received, 143 (90.5%) had a PHEX variant: 14 (9.8%) were variants of uncertain significance (VUS) and 129 (90.2%) were either pathogenic or likely pathogenic (P/LP) XLH molecular diagnoses. Of the 15 patients (9.5%) where no PHEX variant was found, one had a P variant in FGF23 (autosomal dominant hypophosphatemic rickets molecular diagnosis) and another had P and LP variants in ENPP1 (autosomal recessive hypophosphatemic rickets Type 2 molecular diagnosis). Of 159 suspected samples, 101 (63.5%) had a PHEX variant: 14 (13.9%) were variants of uncertain significance (VUS) and 87 (86.1%) were P/LP (XLH molecular diagnoses). No PHEX variant was found for 58 (36.5%) of suspected samples; however, 5 of these had other findings: a dominant-negative heterozygous P variant for ALPL was detected in 3 samples (3 hypophosphatasia, HPP, molecular diagnoses); a fourth carried two P variants in ALPL; a fifth had a LP variant and a VUS in ENPP1 (autosomal recessive hypophosphatemic rickets Type 2). Of 121 unique P/LP PHEX variants detected, 59 were deletions duplications or insertions. A complex rearrangement and an Alu-mediated insertion were detected in the full cohort. To date, additional family member testing was performed for 10 probands with original VUS: in 4 cases the VUS was reclassified to P/LP; 2 were reclassified to P/LP due to more clinical info, highlighting the value of family testing and clinical info to resolve VUS. RNA analyses to resolve VUS and unidentified variants may further improve molecular diagnoses of genetic hypophosphatemia. Program results demonstrate a high diagnostic yield for confirmatory and suspected XLH/ genetic hypophosphatemia.