Operative treatment of isolated epiphyseal fracture of the distal fibula: 1 case report and literature review.

Pediatric ankle injuries are common; ankle epiphyseal fractures are also common in children. But isolated distal epiphyseal fibular fractures of the distal fibula are clinically rare. We describe one unusual case of an adolescent with a completely displaced Salter-Harris type II distal fibular epiphyseal fracture. The attempt of closed reduction failed, and the patient required open reduction and internal fixation. The localized periosteum and the superior peroneal retinaculum were avulsed from the distal fibular metaphysis, with the peroneal tendons underneath exposed but no obvious subluxation. To the best of our knowledge, this combination of injuries has not been previously reported.

Operative Treatment of Distal Tibial Fractures in Children Managed With Epiphyseal Screws: A Comparison of Outcomes When Screws Are Retained Versus Removed Following Fracture Union.

BACKGROUND: Fractures of the distal tibial epiphysis in children are often accompanied by articular surface disruption. With increased displacement, internal fixation is frequently performed with an epiphyseal screw to close the fracture gap. Despite limited, high-level clinical evidence to support implant removal, epiphyseal screws are commonly removed after fracture healing due to potentially increased contact forces on the tibiotalar joint. The purpose of this study was to investigate and compare outcomes and complications in children that underwent surgical treatment of distal tibial epiphyseal fractures with placement of an epiphyseal screw(s) and had the implant(s) retained versus removed at a minimum of 2-year postoperative follow-up. METHODS: Children younger than 18 years from two urban tertiary care centers who underwent operative management of distal tibia Salter-Harris III and IV fractures using epiphyseal screws (2013-2020) were divided into two cohorts: retained epiphyseal screws and implant removed. Demographics, intraoperative, postoperative, and radiographic data were collected. Patient-reported outcomes (PROs) using the Foot and Ankle Ability Measure (FAAM) and Single Assessment Numeric Evaluation (SANE) questionnaires were collected at the final follow-up. Statistical analysis, including power analysis, was performed. RESULTS: Fifty-two children were included (30 males, 22 females) with a mean age of 13.3 years at the time of injury (range, 7.7-16.4 years). Thirty-five children retained the implants; seventeen had implants removed. All completed the FAAM questionnaires at a mean follow-up of 4.4 ± 1.9 years, while 29 completed the SANE questionnaire at a mean follow-up of 4.4 ± 1.7 years. No statistically significant difference in patient demographics, surgical variables, or PROs was observed. Six children experienced complications from the initial surgery, including infections and complex regional pain syndrome, with no difference in complication rates between the cohorts ( P =0.08). Furthermore, no complication was observed as a result of implant removal. CONCLUSIONS: Children with retained epiphyseal implants have similar functional outcomes as compared with those who had implants removed after distal tibial epiphyseal fracture fixation and union. LEVEL OF EVIDENCE: Level III-Retrospective comparative study.

[Epiphyseal fracture of the second metatarsal in adolescents: report of two cases]. / Fractura epifisaria del segundo metatarsiano en adolescentes: reporte de dos casos.

Epiphyseal fractures of the metatarsal head are a rare entity specially as an isolated injury and is rarely seen in patients with skeletal immaturity. Due lack of documentation for this type of fracture, the treatment of choice is uncertain. The purpose of the present study is to present two cases and treatment of epiphyseal fracture of the second metatarsal head, to our knowledge there are no publications for this injury.

Las fracturas epifisarias de la cabeza metatarsiana son una entidad poco frecuente, principalmente cuando se presentan de forma aislada y en raras ocasiones se ven en pacientes con inmadurez esquelética. Debido a la escasez de documentación para este tipo de fractura, el tratamiento de elección es incierto. El motivo del presente estudio es presentar dos casos de fractura epifisaria de la cabeza del segundo metatarsiano y su tratamiento, ya que para nuestro conocimiento no hay publicaciones al respecto.

The mysteries of DNA preservation in bone: A comparative study of petrous bones and metacarpal epiphyses using ATR-FTIR spectroscopy.

A comparative analysis of 26 petrous bones and epiphyses of metacarpals from the Second World War era revealed no significant differences in DNA yield or success in STR typing. This unexpected parity in DNA preservation between the petrous bone, a renowned source of endogenous DNA in skeletal remains, and the epiphyses of metacarpals, which are porous and susceptible to taphonomic changes, is surprising. In this study, we introduced ATR-FTIR spectroscopy as an approach to unravel the correlation between bone molecular structure and DNA preservation. Metacarpals and petrous bones with same taphonomic history were sampled and prepared for DNA analyses. While one portion of the sample was used for DNA analysis, the other underwent ATR-FTIR spectroscopic examination. The normalized spectra and FTIR indices between the epiphyses of metacarpals and petrous bones were compared. Because the taphonomic history of the remains used is relatively short and stable, the ATR-FTIR spectroscopy unveiled subtle structural differences between the two bone types. Petrous bones exhibited higher mineralization, whereas epiphyses contained more organic matter. The unexpected preservation of DNA in the epiphyses of metacarpals can likely be attributed to the presence of soft tissue remnants within the trabeculae. Here observed differences in the molecular structure of bones indicate there are different mechanisms enabling DNA preservation in skeletal tissues.

Bone Age Determination of Epiphyseal Fusion at Knee Joint and Its Correlation with Chronological Age.

Background and Objectives: Bone age determination is a valuable method for forensic and disaster identifications of unknown human remains, as well as for medical and surgical procedural purposes. This retrospective research study aimed to determine the age based on epiphyseal fusion stages and investigate differences related to gender. Materials and Methods: X-rays of the knee were collected from medical imaging centers in hospitals in the south of Jordan and examined by two observers who determined the bone epiphyseal phase of closure for the femur, tibia, and fibula bone ends close to the knee based on a three-stage classification. Results: The main results revealed that females showed earlier epiphyseal union (Stage II) at the lower end of the femur and the upper ends of the tibia and fibula compared to males. In males, the start of complete union (Stage III) at knee bones was seen at the age of 17-18 years, while in females, it was seen at the age of 16-17 years. Additionally, knee bones showed complete union in 100% of males and females in the age groups 21-22 years and 20-21 years, respectively. Although females showed an earlier start and end of epiphyseal complete union than males, analysis of collected data showed no significant age differences between males and females at the three stages of epiphyseal union of the knee bones. Conclusions: Findings of the radiographic analysis of bone epiphyseal fusion at the knee joint are a helpful method for chronological age determination. This study supports the gender and ethnicity variation among different geographical locations. Studies with a high sample number would be needed to validate our findings.

Shape variation and sex differences of the adult human mandible evaluated by geometric morphometrics.

In cases of osseous defects, knowledge of the anatomy, and its age and sex-related variations, is essential for reconstruction of normal morphology. Here, we aimed at creating a 3D atlas of the human mandible in an adult sample using dense landmarking and geometric morphometrics. We segmented 50 male and 50 female mandibular surfaces from CBCT images (age range: 18.9-73.7 years). Nine fixed landmarks and 510 sliding semilandmarks were digitized on the mandibular surface, and then slid by minimizing bending energy against the average shape. Principal component analysis extracted the main patterns of shape variation. Sexes were compared with permutation tests and allometry was assessed by regressing on the log of the centroid size. Almost 49 percent of shape variation was described by the first three principal components. Shape variation was related to width, height and length proportions, variation of the angle between ramus and corpus, height of the coronoid process and inclination of the symphysis. Significant sex differences were detected, both in size and shape. Males were larger than females, had a higher ramus, more pronounced gonial angle, larger inter-gonial width, and more distinct antegonial notch. Accuracy of sexing based on the first two principal components in form space was 91 percent. The degree of edentulism was weakly related to mandibular shape. Age effects were not significant. The resulting atlas provides a dense description of mandibular form that can be used clinically as a guide for planning surgical reconstruction.

Lateral Femoral Condyle Allograft in the Treatment of Elbow Capitellar Avascular Necrosis: A Case Report.

CASE: A 27-year-old woman developed capitellar osteonecrosis after long-term corticosteroid use to treat non-Hodgkin lymphoma. She underwent an osteochondral reconstruction using a lateral femoral condyle (LFC) allograft. This graft was selected because it has a similar radius of curvature to the capitellum. The patient had osseous integration, painless, near full range of motion of her elbow 6 months postoperatively and good shoulder function 1.0 year postoperatively. CONCLUSION: The LFC allograft should be considered a viable option in treating capitellar osteonecrosis.

Determination of the ideal plate for medial femoral condyle fracture fixation: an anatomical fit and biomechanical study.

BACKGROUND: The aim of this study is to determine the best plate to use as a substitute to fix a medial femoral condyle fracture. MATERIALS AND METHODS: The first part is to measure the best fit between several anatomical plates including the Proximal Tibia Anterolateral Plate (PT AL LCP), the Proximal Tibia Medial Plate (PT M LCP), the Distal Tibia Medial Locking Plate (DT M LCP) and the Proximal Humerus (PHILOS) plate against 28 freshly embalmed cadaveric distal femurs. Measurements such as plate offset and number of screws in the condyle and shaft shall be obtained. The subsequent part is to determine the compressive force at which the plate fails. After creating an iatrogenic medial condyle fracture, the cadavers will be fixed with the two plates with the best anatomical fit and subjected to a compression force using a hydraulic press. RESULTS: The PT AL LCP offered the best anatomical fit whereas the PHILOS plate offered the maximal number of screws inserted. The force required to create 2 mm of fracture displacement between the two is not statistically significant (LCP 889 N, PHILOS 947 N, p = 0.39). The PT AL LCP can withstand a larger fracture displacement than the PHILOS (LCP 24.4 mm, PHILOS 17.4 mm, p = 0.004). DISCUSSION AND CONCLUSION: Both the PT AL LCP and the PHILOS remain good options in fixing a medial femoral condyle fracture. Between the two, we would recommend the PT AL LCP as the slightly superior option.

Management of Pediatric Supination-inversion Ankle Injuries Involving Distal Tibia and Intraepiphyseal Distal Fibula Fractures.

Pediatric ankle fractures are prevalent injuries that make up a notable portion of all periphyseal injuries. The Salter-Harris classification is the most popular classification about physeal and periepiphyseal injuries. Ogden expanded on this and described type 7 fractures which are completely intraepiphyseal and include propagation of the fracture from the articular surface through the epiphyseal cartilage and do not involve the physis. These injuries are common about the distal fibula in pediatric patients with supination-inversion type injuries. There are no specific guidelines or recommendations on treatment of these injuries in the literature. We present three cases of this injury pattern and describe our chosen management that leads each patient to full, painless ankle range of motion and return to all prior activities and sports without complication. Supination-inversion type pediatric ankle fractures are common injuries that all orthopaedic surgeons will encounter at some point throughout their practice or training. Recognizing fracture variants and understanding treatment options of pediatric ankle fractures are important for the orthopaedic community as a whole.

Eldecalcitol Induces Minimodeling-Based Bone Formation and Inhibits Sclerostin Synthesis Preferentially in the Epiphyses Rather than the Metaphyses of the Long Bones in Rats.

This study aimed to examine minimodeling-based bone formation between the epiphyses and metaphyses of the long bones of eldecalcitol (ELD)-administered ovariectomized rats. Sixteen-week-old female rats were divided into four groups: sham-operated rats receiving vehicle (Sham group), ovariectomized (OVX) rats receiving vehicle (Vehicle group), or ELDs (30 or 90 ng/kg BW, respectively; ELD30 and ELD90 groups). ELD administration increased bone volume and trabecular thickness, reducing the number of osteoclasts in both the epiphyses and metaphyses of OVX rats. The Sham and Vehicle groups exhibited mainly remodeling-based bone formation in both regions. The epiphyses of the ELD groups showed a significantly higher frequency of minimodeling-based bone formation than remodeling-based bone formation. In contrast, the metaphyses exhibited significantly more minimodeling-based bone formation in the ELD90 group compared with the ELD30 group. However, there was no significant difference between minimodeling-based bone formation and remodeling-based bone formation in the ELD90 group. While the minimodeling-induced new bone contained few sclerostin-immunoreactive osteocytes, the underlying pre-existing bone harbored many. The percentage of sclerostin-positive osteocytes was significantly reduced in the minimodeling-induced bone in the epiphyses but not in the metaphyses of the ELD groups. Thus, it seems likely that ELD could induce minimodeling-based bone formation in the epiphyses rather than in the metaphyses, and that ELD-driven minimodeling may be associated with the inhibition of sclerostin synthesis.

Anterior Proximal Tibial Screw Hemiepiphysiodesis Decreases Posterior Tibial Slope in Knee Flexion Contracture: A Case Report.

CASE: A 13-year-old adolescent boy with hemiplegic cerebral palsy suffering from fixed knee flexion deformity of 10° despite extensive conservative treatment. Owing to a posterior tibial slope (PTS) of 16°, anterior hemiepiphysiodesis was applied to the proximal tibia. The 2 screws were removed after 9 months. Final follow-up at 16 months showed complete knee extension and a PTS of 4°. CONCLUSION: The presented technique is a good alternative in knee flexion deformity with an increased PTS and has surprisingly not been described in the literature. This might be worth considering for other pathologies such as pediatric anterior cruciate ligament injury with an increased PTS.

Correcting for asymmetry of the proximal tibial epiphysis is warranted to determine postoperative alignment deviations in kinematic alignment from planned alignment of the tibial component on the native tibia.

BACKGROUND: In total knee arthroplasty, unrestricted kinematic alignment aims to restore pre-arthritic lower limb alignment and joint lines. Joint line orientations of the contralateral healthy proximal tibia might be used to evaluate accuracy of tibial component alignment post-operatively if asymmetry is minimal. Our objective was to evaluate left-to-right asymmetry of the proximal tibial epiphysis in posterior tibial slope and varus-valgus orientation as related to unrestricted kinematic alignment principles. METHODS: High resolution CT images (0.5 mm slice thickness) were acquired from bilateral lower limbs of 11 skeletally mature subjects with no skeletal abnormalities. Images were segmented to generate 3D tibia models. Asymmetry was quantified by differences in orientations required to shape-match the proximal epiphysis of the mirror 3D tibia model to the proximal epiphysis of the contralateral 3D tibia model. FINDINGS: Systematic and random differences (i.e. mean ± standard deviation) in tibial slope and varus-valgus orientation were - 0.8° ± 1.2° and - 0.2° ± 0.8°, respectively. Ninety five percent confidence intervals on the means included 0° indicating that systematic differences were minimal. INTERPRETATION: Since random differences due to asymmetry are substantial in relation to random surgical deviations from pre-arthritic joint lines previously reported, post-operative computer tomograms of the contralateral healthy tibia should not be used to directly assess accuracy of tibial component alignment on a group level without correcting for differences in tibial slope and varus-valgus orientation due to asymmetry.

Does the intercondylar approach provide a better outcome for chondroblastoma of the distal femur in skeletally immature patients?

Aims: The epiphyseal approach to a chondroblastoma of the intercondylar notch of a child's distal femur does not provide adequate exposure, thereby necessitating the removal of a substantial amount of unaffected bone to expose the lesion. In this study, we compared the functional outcomes, local recurrence, and surgical complications of treating a chondroblastoma of the distal femoral epiphysis by either an intercondylar or an epiphyseal approach. Methods: A total of 30 children with a chondroblastoma of the distal femur who had been treated by intraregional curettage and bone grafting were retrospectively reviewed. An intercondylar approach was used in 16 patients (group A) and an epiphyseal approach in 14 (group B). Limb function was assessed using the Musculoskeletal Tumor Society (MSTS) scoring system and Sailhan's functional criteria. Results: At final follow-up, the mean MSTS score was 29.1 (SD 0.9) in group A and 26.7 (SD 1.5) in group B (p = 0.006). According to Sailhan's criteria, the knee function was good and fair in 14 (87.5%) and two (12.5%) patients of group A, and eight (57.1%) and six (42.9%) patients of group B, respectively (p = 0.062). The lesion had recurred in one patient (6.2%) in group A and four patients (28.6%) in group B. Limb shortening > 1 cm was recorded in one patient (6.2%) from group A and six patients (42.8%) from group B. Joint degeneration was noted in one patient from group A and three patients from group B. Conclusion: An intercondylar approach to a chondroblastoma of the middle two-quarters of the distal femoral epiphysis results in better outcomes than a medial or lateral epiphyseal approach: specifically, better limb function, a lower rate of recurrence, and a lower rate of physeal damage and joint degeneration.

The effect of caponization on tibia bone histomorphometric properties of crossbred roosters.

The negative effect of caponization on the structural, geometric and mechanical parameters of femur and tibia has been shown in a few studies. Nevertheless, its influence on tibia bone microarchitecture is still largely unknown. Therefore, this study aimed to assess the effect of castration on the microstructural parameters of the trabecular and compact bone of tibia bone in crossbred chickens. The experiment involved 96 roosters derived from crossing Yellowleg Partridge hens ([Formula: see text]-33) and Rhode Island Red cockerels (R-11) fattened until the 16th, 20th and 24th week of life. Animals were randomly divided into 2 groups of 48 each. Group I (control) consisted of intact roosters and group II (experimental) consisted of birds subjected to caponization at the 8th week of age. The castration surgery had no influence on some properties within compact bone such as osteon diameter On.Dm, osteon perimeter On.Pm, osteon area On.Ar, osteocyte lacunar number Ot.Lc.N, osteon bone area On.B.Ar, osteon wall thickness On.W.Th as well as thick-mature collagen content in all analyzed age groups of animals. Nevertheless, our results demonstrate that castration caused a decrease of Haversian canal area Hc.Ar, osteocyte lacunar area Ot.Lc.Ar and osteocyte lacunar porosity Ot.Lc.Po among the 16-week-old birds, decrease of Haversian canal perimeter Hc.Pm and increase of fraction of bone area On.B.Ar/On.Ar among 16- and 24-week-old individuals and also an increase of osteocyte lacunar density Ot.Lc.Dn in the osteons of the oldest roosters. Additionally, some microstructural parameters of trabecular bone show the negative effect of caponization. The youngest 16-week-old capons were characterized by thinnin the trabecular in the epiphysis part of tibia. Moreover, in the case of 24-week-old, there is an increase in the trabecular separation Tb.Sp with simultaneous decrease of trabecular number Tb.N compared to roosters, which may suggest the increase of the bone resorption among the oldest individuals. The increased bone turnover in the epiphysis part of the tibia bone also indicates changes in the collagen fibers distribution, where among 20-week-old animals there is a decrease in the content of immature thin collagen fibers with simultaneous increase in the content of mature thick collagen fibers. Furthermore, among the oldest 24-week-old individuals we can observe the increased thick-to-thin collagen ratio, which may be a sign of slowing down in bone formation.

Adolescent idiopathic scoliosis: is there a relationship between Risser staging and the proximal humerus ossification system?

PURPOSE: To evaluate whether there is a mismatch between Risser staging and the proximal humerus ossification system (PHOS); and to analyze the correlation in the skeletal maturity stages between the two humeral epiphyses. METHODS: Data from patients aged 10 to 18 years with adolescent idiopathic scoliosis (AIS) seen between 2018 to 2021 were analyzed. In an anteroposterior (AP) spine radiograph the ossification process was evaluated using the Risser classification method and bilateral PHOS (if both humeral epiphyses were visualized). A mismatch between methods was defined as a Risser 0-1 (relatively skeletally immature) with a PHOS 4-5 (skeletally mature), or a Risser 2-5 (relatively skeletally mature) with a PHOS 1-3 (skeletally immature). The McNemar test was used to calculate the significance of the mismatch. RESULTS: A mismatch between Risser and PHOS stages was observed in 28.5% of 105 patients, which was statistically significant (p < 0.001). Of the 49 patients with a Risser 0-1, 55.1% (n = 27) had a PHOS 4-5. None of the patients with a Risser 2-5 had a PHOS 1-3. In the 47 patients in whom both humeri were visualized, the absolute correlation between the left and right PHOS values was 95.7%. CONCLUSION: Of AIS patients who are relatively skeletally immature according to Risser staging, more than half may be skeletally mature when measured with PHOS. In patients with a Risser 0-1, it is recommended to measure skeletal maturity in an AP spine radiograph using the PHOS method, which may more accurately guide treatment decision-making, without the need to visualize both humeral epiphyses in this radiographic projection. LEVEL OF EVIDENCE: IV.

Factors influencing correction rate following hemiepiphysiodesis using tension band plates for deformities around the knee: a multivariate analysis study.

PURPOSE: The aim of this study was to appraise various factors influencing the correction rate in temporary hemiepiphysiodesis (THE) around the knee joint. Specifically, the study analysed the relationship of correction rate with age, gender, aetiology, type and location of deformity. METHODS: The retrospective study included children who underwent THE for a coronal plane deformity (genu valgus or varum) around the knee joint (distal femur or proximal tibia) over a ten year period (2010-2020). The primary outcome of interest was the correction rate of the deformity. RESULTS: Thirty-three children (27 females and 6 males) with a mean age of 8.1 years involving 86 plates were included in the study. The mean correction achieved was 12.2° over a treatment period of 13.3 months. Subgroup analysis showed significant differences between the type (varus (0.8° per month), valgus (1.1° per month)) and the location of deformity femur (1.2° per month) and tibia (0.7° per month)]. On multivariate analysis, the location and the duration of treatment showed significant associations with the correction rate. CONCLUSION: The correction of coronal deformities following temporary hemiepiphysiodesis is influenced by several factors. Valgus, femoral and deformities in younger children correct at a faster rate. Location of deformity and duration of treatment emerged as potential factors affecting the correction rate.

Corrective Osteotomy and Ligamentous Reconstruction in a Neglected Elbow Dislocation with Radial Neck Malunion: A Case Report.

CASE: Neglected elbow dislocation and radial neck malunion frequently result in chronic pain, instability, and early arthrosis. These complications are best prevented by early treatment with open reduction, corrective osteotomy, and ligament reconstruction, followed by early supervised physiotherapy. We present a peculiar case with neglected complex elbow dislocation and radial head malunion. In this case, we performed an open reduction of the elbow joint and radial neck corrective osteotomy, medial collateral ligament, annular ligament reconstruction, and lateral collateral ligament repair. CONCLUSION: Neglected complex elbow dislocations require reconstruction of both ligamentous and osseous structures to achieve a good functional outcome.

Bone age assessment based on different MRI modalities of the proximal humerus epiphysis: the comparisons of T1WI, T2WI, and PDWI.

Bone age assessment (BAA) is crucial in various fields, including legal proceedings, athletic competitions, and clinical medicine. However, the use of X-ray methods for age estimation without medical indication is subject to ethical debate, especially in forensic and athletic fields. The application of magnetic resonance imaging (MRI) with non-ionizing radiation can overcome this limitation in BAA. This study aimed to compare the application value of several MRI modalities of proximal humeral in BAA. A total of 468 patients with shoulder MRIs were retrospectively collected from a Chinese Han population aged 12-30 years (259 males and 209 females) for training and testing, including T1 weighted MRI (T1WI), T2 weighted MRI (T2WI), and Proton density weighted MRI (PDWI). Optimal regression models were established for age estimation, yielding mean absolute error (MAE) values below 2.0 years. The MAE values of T1WI were the lowest, with 1.700 years in males and 1.798 years in females. The area under the curve (AUC) and accuracy values of different MRI modalities of 16-year and 18-year thresholds were all around 0.9. For the 18-year threshold, T1WI outperformed T2WI and PDWI. In conclusion, the three MRI modalities of the proximal humerus can serve as reliable indicators for age assessment, while the T1WI performed better in age assessment and classification.

Natural history of Wolcott-Rallison syndrome: A systematic review and follow-up study.

BACKGROUND AND AIMS: To systematically review the literature for reports on Wolcott-Rallison syndrome, focusing on the spectrum and natural history, genotype-phenotype correlations, patient and native liver survival, and long-term outcomes. METHODS: PubMed, Livio, Google Scholar, Scopus and Web of Science databases were searched. Data on genotype, phenotype, therapy, cause of death and follow-up were extracted. Survival and correlation analyses were performed. RESULTS: Sixty-two studies with 159 patients met the inclusion criteria and additional 30 WRS individuals were collected by personal contact. The median age of presentation was 2.5 months (IQR 2) and of death was 36 months (IQR 50.75). The most frequent clinical feature was neonatal diabetes in all patients, followed by liver impairment in 73%, impaired growth in 72%, skeletal abnormalities in 59.8%, the nervous system in 37.6%, the kidney in 35.4%, insufficient haematopoiesis in 34.4%, hypothyroidism in 14.8% and exocrine pancreas insufficiency in 10.6%. Episodes of acute liver failure were frequently reported. Liver transplantation was performed in six, combined liver-pancreas in one and combined liver-pancreas-kidney transplantation in two individuals. Patient survival was significantly better in the transplant cohort (p = .0057). One-, five- and ten-year patient survival rates were 89.4%, 65.5% and 53.1%, respectively. Liver failure was reported as the leading cause of death in 17.9% of cases. Overall survival was better in individuals with missense mutations (p = .013). CONCLUSION: Wolcott-Rallison syndrome has variable clinical courses. Overall survival is better in individuals with missense mutations. Liver- or multi-organ transplantation is a feasible treatment option to improve survival.