De novo TRPM3 missense variant associated with neurodevelopmental delay and manifestations of cerebral palsy.

We identified a de novo heterozygous transient receptor potential cation channel subfamily M (melastatin) member 3 (TRPM3) missense variant, p.(Asn1126Asp), in a patient with developmental delay and manifestations of cerebral palsy (CP) using phenotype-driven prioritization analysis of whole-genome sequencing data with Exomiser. The variant is localized in the functionally important ion transport domain of the TRPM3 protein and predicted to impact the protein structure. Our report adds TRPM3 to the list of Mendelian disease-associated genes that can be associated with CP and provides further evidence for the pathogenicity of the variant p.(Asn1126Asp).

Orthopaedic Diagnoses in the Black Pediatric Population.

The Black pediatric population is one that has been historically underserved and continues to have unmet needs. Factors including lack of diversity in orthopaedic studies and in historical standards, such as bone age, may inadvertently lead to inferior care. There are certain conditions in this population for which the practicing orthopaedic surgeon should have a higher degree of suspicion, including slipped capital femoral epiphysis, Blount disease, and postaxial polydactyly. Systemic diseases with higher rates in this population have orthopaedic manifestations, including sickle cell disease, vitamin D deficiency, and obesity. Racial discrepancies in access to prenatal care can have orthopaedic consequences for babies, especially cerebral palsy and myelodysplasia. Racial discrepancy exists in evaluation for nonaccidental trauma. Increased awareness of these issues better prepares practitioners to provide equitable care.

Patient-Reported Outcome Measurement Information System (PROMIS) Scores in Pediatric Idiopathic Toe Walkers.

BACKGROUND: Idiopathic toe walking (ITW) can result in early contact with the health care system and be distressing for patients and their families. The natural history of ITW is poorly characterized. Deciding how and when to intervene can be difficult.Patient-reported outcomes are utilized in the clinical setting to assess patient factors and indications that may better inform treatment plans. Patient-Reported Outcomes Measurement Information System (PROMIS) is an instrument designed to collect patient-reported outcomes. Minimum clinically important differences in PROMIS metrics have been established to facilitate clinical relevance and utility of these metrics. The purpose of this study was to characterize the patient perspective of ITW by utilizing the PROMIS scores. METHODS: Retrospective chart review was performed to identify children aged 5 to 17 with a diagnosis of ITW treated at a single tertiary care center between 2017 and 2020. Inclusion criteria were a diagnosis of ITW and completion of a PROMIS questionnaire. Exclusion criteria were neurologic disease, autism, and previous surgical treatment. Demographic, physical exam, treatment, and available motion analysis data were collected. PROMIS scores for the following domains were available: Mobility, Peer Relationships, and Pain Interference. RESULTS: Forty-five children were enrolled. Seventy-three percent of PROMIS scores were patient reported while the remainder were parent reported. PROMIS score means for the cohort by domain were Mobility: 45.2±8.2 ( P <0.000); Peer Relationships: 46.4±11.6 ( P =0.047); and Pain Interference: 47.4±9.5 ( P =0.67). Motion analysis data, available for 11 children, noted age-matched gait velocity negatively correlated ( rs =-0.652, P =0.03) with Peer Relationships. No correlations were found between other aspects of gait, body mass index, or limitations in dorsiflexion and PROMIS domains. Parents reported lower Mobility scores than children did. There were no other significant differences between patient-reported and parent-reported PROMIS scores. PROMIS scores did not differ significantly between those <10 years and those ≥10 years. CONCLUSION: In this cohort of 45 otherwise healthy children without other neurologic diagnoses, there are both clinically and statistically significant differences in PROMIS means between our cohort and the healthy age-matched population. These differences manifested in worse peer relationships and mobility scores. LEVEL OF EVIDENCE: Level IV.

An Unusual Presentation of Osteogenesis Imperfecta: A Case Report.

CASE: We report an 18-year-old patient with a clinical phenotype consistent with severe osteogenesis imperfecta (OI) with frequent fractures, short stature, shortening and bowing of extremities, and unusual radiographic features of severe fibrous dysplasia, including lytic lesions and a "ground-glass" appearance. Genetic testing for the patient was notable for a c.119C>T (p.Ser40Leu) variant in exon 1 of IFITM5 and a c.676C>A (Pro226Thr) variant in exon 5 of CREB3L1. CONCLUSION: This unusual skeletal presentation was in the setting of a rare IFITM5 mutation and represents a unique case of severe OI.

Can Patients and Families Read the Questionnaires for Patient-related Outcome Measures?

BACKGROUND: Patient-reported Outcome Measures (PROMs) quantifying health-related quality of life are widely used to evaluate illness and the impact of health care interventions. The questionnaires must be comprehensible by the persons completing them. Literacy Surveys in the United States reveal nearly half of the US adult population have a literacy level below the 8th grade. Recommendations are that health-related written material directed at adults should be at a reading level of grade 6 or below. Reading level for materials aimed at minor patients should be no higher than their grade level. Our aim was to determine the readability of pediatric orthopaedic PROMs as determined by a validated literacy tool. METHODS: A literature search was conducted to identify PROMs cited in pediatric orthopaedics. In total, 79 PROMs were identified. Only text-based PROMs that were developed in English for pediatrics and have published evidence of validation were included, leaving 35 outcome scores for analysis. Text was extracted and analyzed using the Flesch Reading Ease Score (FRES). RESULTS: Of 35 PROMs: 15 (43%) were general, 12 (34%) spine, 5 (14%) lower, and 3 (9%) upper extremity. Ten (29%) were designed to be completed by the caregiver, whereas 25 (71%) by the patient. Ten PROMs intended for completion by a parent had an FRES readability of 8th to 10th grade level with only 2 of 10 corresponding to that would be understood by the average adult. Of the 25 PROMs intended for completion by pediatric patients, only 4 (16%) had a FRES corresponding with the age group intended to complete them. CONCLUSIONS: The majority of PROMs are written at a level of complexity higher than likely to be understood by the persons intended to complete them. This is of significance, given that researchers and practitioners alike rely on data from PROMs in drawing conclusions about the impact of orthopaedic conditions and their treatments on health-related quality of life. Analysis of easily comprehended PROMs will aid in the design of future scores to maximize their utility in research and clinical practice. LEVEL OF EVIDENCE: Level II-decision analysis study.

The Epidemiology of Slipped Capital Femoral Epiphysis in American Samoa.

The Maori of New Zealand have been identified as a high-risk population for slipped capital femoral epiphysis (SCFE). This study assessed whether the burden of disease from SCFE in the American Territory of American Samoa is similar to that identified in the Maori. This was a retrospective review of children from American Samoa treated for SCFE at a tertiary care pediatric hospital between 2005-2014. Demographic, clinical, and radiographic information was collected. All patients were followed for at least one year after surgery and prophylactically pinned hips were not included. Data for determining incidence was obtained from the United States Census Bureau. Between 2005-2014, 55 American Samoan youth were treated for 73 SCFE. The incidence in the "at-risk" population 5-14 years of age was 53.1 per 100,000. Patients had a mean BMI of 29.5 (19.4-46.4) and mean weight of 76.7 kg (45.9-139 kg). Southwick angle was a mean 40.6°+/- 20.4° (6-83°). Overall, 82.2% of hips were treated with in-situ cannulated screw fixation. At a minimum one-year after initial surgery, 22 hips (30.1%) required major surgery including intertrochanteric osteotomy, osteochondroplasty, or total hip replacement. The incidence of SCFE in American Samoa is extremely high, 53.1 per 100,000 of "at-risk" population 5-14 years old. The mean weight and BMI in SCFE patients from American Samoa is substantially higher than previously published reports. Furthermore, morbidity from SCFE in this population is substantial with 30.1% requiring major surgery either at the time of physeal stabilization or in subsequent years.

Current State of the Opioid Epidemic as it Pertains to Pediatric Orthopaedics From the Advocacy Committee of the Pediatric Orthopaedic Society of North America.

INTRODUCTION: The opioid epidemic in the United States has reached crisis proportions. Urgent response is needed. Hydrocodone in combination with acetaminophen is the most prescribed drug in the United States. The most common source of opioids available for misuse is the unused portions of postoperative prescriptions. Among high school seniors, 80% of those who reported nonmedical use of prescription opioids previously had legitimate prescriptions but recreationally used leftover doses. Roughly one-quarter of patients do not take any of their postoperatively prescribed opioids and the remainder take one-third to two-thirds of the prescribed doses. METHODS: A summary of the literature is presented beginning from historical perspective to current status and pertinent strategies in dealing with this complicated problem. This review includes data from an electronic survey of the members of the Pediatric Orthopaedic Society of North America (POSNA) with regard to the prescriptions they would provide for 7 treatment scenarios. RESULTS: Strategies for the preoperative, intraoperative, and postoperative phases of management of pain as well as strategies for education, research, and advocacy are presented. The Pediatric Orthopaedic Society of North America survey yielded 264 respondents. The 3 most commonly used opioid medications were hydrocodone, oxycodone, and acetaminophen with codeine, in that order, for most of the scenarios. The time period covered by postoperative prescriptions varied considerably. CONCLUSIONS: The magnitude of this problem is overwhelming. Education of care providers, patients and families, standardization of narcotic prescribing practices which incorporate patient characteristics, and appropriate plans for disposal of unused narcotics are immediate concepts to consider in correcting this problem. Long-term issues to tackle will be changing patient a family expectations, legislation, and obtaining additional resources directed towards this issue.

Bilateral navicular-medial cuneiform synostosis manifesting as medial foot pain: a case report and review of the literature.

Isolated navicular-medial cuneiform tarsal coalition is a rare condition. Very few case reports exist, with limited treatment recommendations. We present a case of an 11-year-old with bilateral isolated osseous navicular-medial cuneiform tarsal coalition. The patient was treated with bilateral coalition excision and soft tissue interposition, with excellent results at 2 years of follow-up. The current case is unusual in being an osseous coalition rather than the more commonly seen cartilaginous or fibrous condition. In addition, this case is uncommon as being in a patient of European rather than Asian descent.

Safety and Efficacy of Botulinum Toxin A in Children Undergoing Lower Limb Lengthening and Deformity Correction: Results of a Double-blind, Multicenter, Randomized Controlled Trial.

BACKGROUND: Lengthening of the lower limb is a complex procedure in which pain management and complications such as pin-site infections and muscle contractures impact the family and affect the child's quality of life. As a result, the paralytic and antinociceptive actions of neurotoxins may be indicated in managing these complications; however, few studies have explored ways to improve outcomes after lengthenings. The objective of this study was to evaluate the safety and efficacy of botulinum toxin A (BTX-A) in children undergoing lower limb lengthenings and deformity correction. METHODS: Participants with a congenital or acquired deformity of the lower extremity requiring surgery to one limb were randomized to receiving either BTX-A as a single dose of 10 units per kilogram body weight, or an equivalent volume of saline solution. Pain, medication, quality of life, and physical function were assessed at different time-points. Adverse events were recorded in all participants. T test and χ tests were used to compare potential differences across both groups. RESULTS: Mean age of the 125 participants was 12.5 years (range, 5 to 21 y), and lengthenings averaged 4.2 cm. Maximum pain scores on day 1 postoperatively were lower in the BTX-A group (P=0.03) than in the placebo group, and remained significant favoring botox when stratifying by location of lengthening (femur vs. tibia). Clinical benefits for BTX-A were found for 3 quality of life domains at mid-distraction and end-distraction. When stratifying according to location of lengthening, there were significantly fewer pin-site infections in the tibia favoring botox (P=0.03). The amount of adverse events and bone healing indices were no different in both groups. CONCLUSIONS: The clinical differences in quality of life, the lower pain on the first postoperative day, and the lower number of pin-site infections in the tibia favoring BTX-A support its use as an adjunctive treatment to the lengthening process. The detailed analyses of pain patterns help inform families on the pain expectations during lower limb lengthenings. The amount of adverse events were no different in both groups, and bone healing rates were similar, indicating that the use of BTX-A in children undergoing limb lengthening and deformity correction is safe. LEVEL OF EVIDENCE: Level I.

Complications of supracondylar osteotomies for cubitus varus.

BACKGROUND: Humeral osteotomies for cubitus varus have a notoriously high complication rate. Pitfalls of this difficult procedure are highlighted. METHODS: A 50-year experience of 68 consecutive surgeries was reviewed. Factors such as surgical approach and fixation technique were compared for complication incidence and type. RESULTS: Seventeen patients (25%) had 23 (34%) clinically remarkable complications. Nine postoperative nerve palsies occurred in 8 patients. Loss of reduction requiring revision or manipulation was seen in 3 patients. The following complications were noted in 2 patients each: nonunion, loss of flexion, lateral prominence, and unsatisfactory scar. Growth arrest, osteomyelitis, and under-correction requiring revision each occurred once. A lateral, triceps-sparing approach was associated with an overall prevalence of complications of 24% (5 of 21) equivalent to the posterior, triceps splitting approach of 24% (10 of 42). An olecranon osteotomy was used in 2 patients both with complications. No nerve injuries occurred in patients who underwent a lateral approach, whereas nerve palsies occurred in 14% (6 of 42) of the patients where a posterior approach was used. An olecranon osteotomy was used in 2 patients with nerve injury occurring in both. A medial approach in 2 patients and a combined medial-lateral approach in 1 patient were used with no complications. Plate and screw fixation was implemented in 29 cases with complications occurring in 6 of them; pin fixation, in 30 cases, 7 of which had complications. There was a higher incidence of under-correction requiring additional surgery with plate fixation (1 of 29) compared with pin fixation which had no under correction but had loss of fixation in 2 of 30. The average correction obtained was similar in the group with complications (32 degrees) versus those without (27 degrees). CONCLUSIONS: Supracondylar humeral osteotomy is a technically demanding procedure fraught with complications. Plate fixation and pin fixation techniques resulted in similar complication rates, but the surgical approach used appeared to make a difference. The posterior, triceps splitting, approach resulted in a high incidence of nerve palsies versus none with the lateral, triceps-sparing approach. LEVEL OF EVIDENCE: This is a retrospective case series, Level IV.

Botulinum toxin type A injection in alleviating postoperative pain and improving quality of life in lower extremity limb lengthening and deformity correction: a pilot study.

BACKGROUND: The Ilizarov technique is commonly used for lengthening and deformity corrections of the lower limbs in children. Postoperative pain can be significant, affecting quality of life and functional mobility, and often requiring prolonged medication use. Several studies have investigated the antinociceptive actions of botulinum toxin type A (BtX-A), yet evidence for its use in this population is limited. The objectives were to (1) establish the feasibility of a randomized clinical trial in children undergoing limb lengthening or deformity correction and (2) provide preliminary evidence of the beneficial effects of BtX-A in this population. METHODS: Fifty-two patients with a mean age of 13.7 years (range, 5 to 21 y) were randomized to receive either BtX-A or an equivalent volume of sterile saline solution (placebo group), as a single dose during the surgical procedure. Pain, medication use, quality of life, and functional mobility outcomes were assessed in all patients. Adverse events were reported for all patients and classified as minor or major. RESULTS: Differences between groups did not reach statistical significance; however, pain at mid-distraction was found to be slightly lower in the BtX-A group, as compared with the placebo group. Patients in the BtX-A group used less parenteral pain medication in the first 4 days after the surgery, had higher quality of life scores at 3 of the 5 time points assessed, and slightly higher functional mobility scores. All adverse events were expected complications of the lengthening process. No event was considered to be a serious adverse event related to the BtX-A injection itself. There was a trend toward fewer major adverse events in the BtX-A group. CONCLUSIONS: This pilot study established the feasibility of a randomized controlled trial design for in this population. Its findings indicate that BtX-A injections appear to be safe and effective for reducing pain and improving the quality of life and functional mobility of children undergoing lengthening or deformity corrections of the lower limbs. A larger-scale study is currently underway to confirm these preliminary findings.

Transient monoparesis after blade plate removal in a Hutchinson-Gilford progeria syndrome patient: a case report.

Treatment of patients with Hutchinson-Gilford progeria syndrome (HGPS) is based on the abnormalities of accelerated aging that affect the healing processes, combined with a fragile cardiovascular status. A classic HGPS case, of Korean ancestry, previously treated for severe coxa valga with bilateral varus osteotomies using blade plate fixation is presented. Complications over the blade plate area required removal of the hardware, after which the patient showed right-sided hypertonicity--determined to be a cerebrovascular accident. Subsequently, the patient returned almost completely to her presurgical neurologic status. Perioperative planning for HGPS patients should include risks that are typically considered in the planning for geriatric patient care.

Pin-tract infection during limb lengthening using external fixation.

We evaluated the incidence of pin-tract infection (PTI) during limb lengthening using external fixation in 88 patients and the effects of infection on final outcomes and incidence of additional procedures. The PTI rate was 96.6%. The rate of half-pin site infection was significantly (P<.05) higher in half-pin fixators (100%) than in hybrid fixators (78%). There was a significantly (P<.05) higher incidence of half-pin site infection (78%) than fine-wire site infection (33%). The rate of additional surgeries for treating PTI was higher for half-pin sites than for fine-wire sites. Three (3.4%) of the 88 cases led to chronic osteomyelitis. Careful insertion and a simple, well-defined, excellent pin-care protocol can minimize PTI.

Evidence-based analysis of removal of orthopaedic implants in the pediatric population.

BACKGROUND: Requested project of the Pediatric Orthopaedic Society of North America Evidenced-Based Medicine Committee. METHODS: The English literature was systematically reviewed for scientific evidence supporting or disputing the common practice of elective removal of implants in children. RESULTS: Several case series reported implant removal, but none contained a control group with retained implants. No articles reported long-term outcomes of retained implants in large numbers. Several small series describe complications associated with retained implants without evidence of causation. The existing literature was not amenable to a meta-analysis. By compiling data from the literature, it is possible to calculate a complication rate of 10% for implant removal surgery. The complication rate for removal of implants placed for slipped capital femoral epiphysis is 34%. Articles regarding postmarket implant surveillance and basic science were also reviewed. CONCLUSIONS: There is no evidence in the current literature to support or refute the practice of routine implant removal in children.

Comparison of distraction osteogenesis for congenital and acquired limb-length discrepancy in children.

This study evaluated 116 lower limb lengthenings in 88 consecutive patients (mean age, 13.5 years) treated for congenital (31 patients [46 lengthened segments]) and acquired (57 patients [70 lengthened segments]) limb-length discrepancy. Mean follow-up was 3.8 years. Mean lengthening index was 34+/-16 days/cm in the congenital group and 32+/-9 days/cm in the acquired group; this difference was not statistically significant (P> .05). Mean length of distraction regenerate was 6.4+/-3.7 cm in the congenital group and 5.7+/-2.9 cm in the acquired group; this difference was not statistically significant (P> .05). Lengthening percentage was significantly higher in the congenital group (25+/-17.6) than in the acquired group (19+/-15.4). The increase in the complications rate in congenital limb-length discrepancy correlates with a significantly higher lengthening percentage. Bone regenerate is produced equally regardless of whether the etiology is acquired or congenital.

Trevor's disease: the clinical manifestations and treatment of dysplasia epiphysealis hemimelica.

Trevor's disease is a rare abnormality characterized by aberrant osteocartilaginous growth from an epiphysis. We describe six new cases from our institution. A patient with isolated tibial tuberosity involvement is described for the first time. Each patient was classified according to Azouz into localized (three), classical (two) and generalized (one) form. We recommend that parents be counseled regarding the progressive nature of this disorder owing to the chance of worsening deformity with surgical excision alone, and the need to be followed until skeletal maturity.

Bone lengthening in children: how to predict the complications rate and complexity?

PURPOSE: Complications arising from limb-lengthening procedures are often severe leading to long-term residuals. The aim of this study was to determine whether the complication rate and complexity could be predicted using a distraction index for bone lengthening in children. STUDY DESIGN: This study retrospectively reviewed a series of 116 lower limbs lengthening in 88 consecutive patients (mean age 13.5). Mean follow-up 3.8 years. Lengthening percentage, lengthening index, distraction regenerate length, additional surgeries, and complications rate were used to evaluate the results of limb lengthening. The correlation between lengthening percentage and complication rate was particularly analyzed and its practicability illustrated. Scatter plots of complication rate (%) against lengthening percentage were constructed, and linear regression was used to investigate mathematical relationship between the variables. RESULTS: The lengthening index was 33 +/- 12.1 days/cm. The length of distraction regenerate was 6 +/- 3.2 cm. The lengthening percentage was 21 +/- 16.5. The scatter plots of neurological complication rate, residual deformities rate, broken pins rate, joint contractures rate, and hypertension rate against lengthening percentage showed a positive linear relationship with r = 0.8. CONCLUSIONS: The number of complications increased considerably with the increase in lengthening percentage. The lengthening percentage correlates very well with the complication rate and can be used to predict the complication rate. CLINICAL RELEVANCE: During planning a lengthening procedure, the lengthening percentage should be a useful tool to predict the complications rate and to discuss the risks and benefits with patients and their families. The knowledge about predictable complications should help prevent and early detect expected complications.

Transfixion wire positioning within the bone: an option to control proximal tibia external fixation stiffness.

PURPOSE: The greatest angle that can be formed by the crossing wires at the proximal tibia level without altering safe corridors approaches only 60 degrees. Consequently, the wires are positioned more in the coronal than the sagittal plane. Looking for an increase in sagittal bending stiffness, we evaluated different wire positioning within the proximal tibia and their effect on the stiffness of external fixation of proximal tibia. STUDY DESIGN: A fiberglass composite tibia fixed into an idealized ring external frame was tested with a servohydraulic test frame. Load-deformation behavior was compared among the different wire positioning within the proximal tibia under identical conditions of central axial compression, medial compression-bending, posterior compression-bending, posteromedial compression-bending, and torsion. Stiffness values were calculated from the load-deformation and the torque-angle curves. RESULTS: The sample with 3 wires positioned within the bone-2 wires crossed 1 cm posteriorly from the center of the tibia and the third wire placed in coronal plane 1 cm anteriorly from the center of the tibia-was significantly (P < 0.05) stiffer in posterior, posteromedial, and torsional loading configurations compared with all other wire positions within the bone. CONCLUSIONS: This new wire positioning within the proximal tibia-2 wires crossed 1 cm posteriorly from the center of the tibia and the third wire placed in coronal plane 1 cm anteriorly from the center of the tibia-increased overall stiffness of external fixation, predominantly in sagittal plane. CLINICAL RELEVANCE: This work provides a rationale to control proximal tibia external fixation stiffness in sagittal plane.

Precocious osteoarthritis in a family with recurrent COL2A1 mutation.

OBJECTIVE: To examine the genotypic and phenotypic characteristics of a Micronesian kindred with autosomal dominant precocious osteoarthritis (OA). METHODS: We reviewed records and radiographs of 3 index patients and their parents, administered questionnaires to 16 additional kindred members, performed whole-genome scans of 24 family members, and sequenced relevant genes from 16 family members. RESULTS: The kindred displayed early onset OA, enlarged epiphyses, platyspondyly, and brachydactyly with dysplastic findings consistent with mild spondyloepiphyseal dysplasia. Genetic analysis revealed an arginine to cysteine substitution at position 75 of the collagen 2A1 gene, a mutation that has been described in 4 other geographically distinct families. The major phenotypic differences among the families were in height (ranging from short to tall) and hearing loss noted in 3 of the 5 families. CONCLUSION: The presence of the COL2A1 Arg75Cys mutation in 5 geographically distinct areas helps to confirm a potential mutational hotspot. The diverse phenotypic spectrum suggests that modifier genes and environmental factors play a role in the expression of this mutation.

Axial deformity correction in children via distraction osteogenesis.

We performed a retrospective analysis of the results of 62 tibial and 54 femoral lengthenings in 88 consecutive patients. The patients mean age was 13.5 years and mean follow-up was four years. There was a significant difference between metaphyseal (27+/-1.2 days/cm) and diaphyseal (39.4+/-1.7 days/cm), tibial (34+/-1.7 days/cm) and femoral (31+/-1.4 days/cm) lengthening (P<0.05), but no significant difference among the lengthening indexes when treating one-, two-, or three-dimensional deformities, congenital (34+/-2.4 days/cm) and acquired (32+/-1.0 days/cm) limb length discrepancy (LLD) (P>0.05). The lengthening index was 33+/-1.1 days/cm, distraction regenerate length 6+/-0.4 cm, and lengthening percentage 21+/-2.1. The scatter plots of new regenerate length against time and the scatter plots of neurological complication, residual deformities, broken pins, joint contractures, and hypertension rate against lengthening percentage showed a positive linear relationship (r=0.8). We found the correlations between quantitative and qualitative parameters that should help to predict the treatment outcomes. Lengthening index depends on the amount of length gained. Higher length of new bone regenerate leads to a decrease in lengthening index. Expected gain in bone length can aid in estimating the duration of treatment. The lengthening percentage correlates very well with the complication rate and can be used to predict the complication rate.