Prenatal diagnosis (or lack thereof) of arthrogryposis multiplex congenita and its impact on the perinatal experience of parents: A retrospective survey.

OBJECTIVE: To examine parental experiences during pregnancies affected by Arthrogryposis Multiplex Congenita (AMC) by identifying commonalities, risk factors, and areas for improvement in detection rates, care protocols, and patient experience. STUDY DESIGN: An online survey was distributed via AMC support groups on Facebook. Topics included demographics, risk factors, parental recall of sonographic findings, delivery characteristics and neonatal findings. Responses were divided into antenatally detected cases (ADCs) and postnatally detected cases (PDCs). Quantitative responses were analyzed with the Fisher exact test. Qualitative data were analyzed with thematic analysis. RESULTS: The antenatal detection rate of arthrogryposis was 37%. Decreased fetal movement was reported by 53% and early bleeding by 21%. Sonographic findings in ADCs included clubfoot (83%), clenched hand (51%), decreased fetal movement (50%), elbow contracture (51%), and knee contracture (46%). Among ADCs, 29% delivered vaginally and 71% delivered by cesarean versus PDCs (44% vaginal, 56% cesarean). Neonatal intensive care unit admission rate was 63%. Bone fracture occurred in 9%. Detection led to a planned change in delivery mode in 33% and location in 50%. Among ADCs, 17% felt their concerns were not adequately addressed versus 43% of PDCs. CONCLUSIONS: Antenatal detection of arthrogryposis was low. We propose enhanced screening criteria to aid prenatal diagnosis and promote utilization of more robust practice guidelines.

Role of Body Cast Application for Scoliosis Associated With Prader-Willi Syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a rare genetic syndrome, with a prevalence of infantile scoliosis of ~23%. These curves are likely related to severe hypotonia. Approximately 15% of children with PWS will need surgical intervention for their scoliosis. The purpose of this study was to evaluate the effectiveness of curing or controlling moderate and severe infantile scoliosis curves in children with PWS. METHODS: This single institution, retrospective study of patients with PWS and infantile scoliosis reviewed 34 consecutive children with >24 months follow-up from initiation of serial spinal casting. Cobb angle comparison measurements of radiographs taken precasting, during treatment, and at follow-up were performed. Rib-vertebral angle difference, Nash-Moe rotation, and space available for lung measurements were followed. Outcomes were stratified as "Cured," "Braced," and "Surgery." RESULTS: Average age for first cast for the entire study was 32 months (range, 14 to 64), undergoing 8 casts (range, 3 to 18) over 25 months (range, 9 to 57) for an initial curve of 54 degrees (range, 27 to 106 degrees), which improved to 27 degrees (range, 11 to 78 degrees). In total, 12 patients (35%) were in the Cured group, following 6 casts over 17 months, with an initial curve of 44±14 degrees improving to 17±5 degrees at the end of treatment, and 20±18 degrees at 68-month follow-up. In total, 18 patients were in the Braced group, with curves initially improving from 55±14 degrees to 35±14 degrees, but at 47±20 degrees at 51-month follow-up. Four patients needed surgery, with initial curves 85 degrees (range, 54 to 106 degrees), but surgery could be postponed 56 months (range, 40 to 73) by casting. Rib-vertebral angle difference was not prognostic. CONCLUSIONS: Serial spinal casting is effective in for treating infantile scoliosis in children with PWS. One third of patients had their curve resolved, at least temporarily, where they were braced and cast free. The others were able to delay surgery for a number of years. Initial curves <50 degrees in children <3 years of age seem to have the best prognosis. LEVEL OF EVIDENCE: Level IV.

Orthopaedic care of the child with arthrogryposis: a 2020 overview.

PURPOSE OF REVIEW: The orthopaedic treatment of children with arthrogryposis multiplex congenita has evolved steadily over the past two decades. Interrelated factors have spurred this on, including better appreciation of the functional potential of persons with arthrogryposis, development of newer procedures specific for the arthrogrypotic deformities, and outcomes studies that provide understanding of the overall capabilities of adults with arthrogryposis and follow-up to determine which treatments were beneficial and which were not. This article briefly sketches out of some of these advances and indicates areas that need further development. RECENT FINDINGS: Outcome studies show that the majority of adults with arthrogryposis are ambulatory but less than half are fully independent. Adults frequently experience ongoing pain, particularly foot and back pain, limiting ambulation and standing. Advancements in the upper extremity treatment include improving elbow function, wrist repositioning, and improving thumb positioning. In the lower extremities, correction of hip and knee contractures leads to improved ambulatory potential, and treating clubfeet with serial casting decreases poor outcomes. SUMMARY: Clinical evaluation, both physical examination and assessment of the patient's needs, are important in directing treatment in arthrogryposis. Further outcomes studies are needed to continue to refine procedures and define the appropriate candidates.

Comparison of Hip and Knee Arthroplasty Rates of Individuals With and Without Prader-Willi Syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a complex genetic condition, affecting between 1:10,000 and 1:30,000. The prevalence of hip dysplasia in children with PWS is reportedly between 8% and 30%, but the long-term consequences of residual hip dysplasia remain largely unknown in this population. The purpose of this study was to comparatively estimate the number of total hip arthroplasty (THA) and total knee arthroplasty (TKA) procedures performed on adults with and without PWS, using a national hospital discharge database, in an effort to elucidate long-term outcomes and guide clinicians treating orthopaedic concerns in younger individuals with PWS. METHODS: The National Inpatient Sample of the Healthcare Cost and Utilization Project is the largest all-payer inpatient care database, containing annual data from >7 million hospital stays; sampling weights and stratification variables are provided for producing estimates of >35 million hospitalizations nationwide. THA and TKA procedures were identified, then stratified by whether or not the patient had a diagnosis of PWS. The ages of the 2 groups and sex mix were compared, as was the length of stay for the procedure, and discharge status. RESULTS: From 2004 to 2014, 9.4 million patients nationwide, by weighted estimate, underwent THA (3.1 million) or TKA (6.3 million). Sixty-five patients were identified as having the diagnosis of PWS (39 with THA, 26 with TKA); 7 patients per million having hip or knee arthroplasties had PWS. Sixty-eight percent of those with PWS were younger than 50 years, compared with only 7% of those without PWS (P<0.001). The female:male prevalence was 47:53 for patients with PWS and 60:40 for the total group. The mean length of stay was similar, but patients with PWS were more likely to be transferred to another facility after surgery (77% vs. 36%; P=0.008). CONCLUSIONS: Hip dysplasia prevalence is higher in persons with PWS, but the rate of late treatment with THA is much lower than in the general population. We recommend only active observation for stable and improving hips in young children with PWS, as the consequences of overtreatment can be serious, including further delaying their neuromuscular development, and exposure to possibly unnecessary perioperative risks. LEVEL OF EVIDENCE: Nation-wide database analysis, Level IV.

Research platform for children with arthrogryposis multiplex congenita: Findings from the pilot registry.

A pediatric registry for arthrogryposis multiplex congenita (AMC) proposes to advance research by providing the platform to inform the distribution, etiology, and natural history of AMC. The registry was piloted on 40 families of children (mean = 8.25 years, 48% males) presenting with AMC across two hospitals in North America. Data on the child's demographic and newborn variables, mothers' and fathers' demographic variables, lifestyle habits, and medical history were collected using a telephone interview with the primary caregiver and review of medical charts. Mean gestational age was 38 weeks, 97% of children presented with lower extremity deformities, and 74% of neonatal interventions targeted the lower extremity. Newborns spent an average of 14 days in the hospital (range 2-56 days) mostly for diagnostic workup and feeding difficulties. Half (49%) of the sample had internal organ involvement. Genetic testing was done on 48% of the children, including chromosome studies, single gene, whole-exome/genome sequencing, and/or microarray studies. Genetic findings were inconclusive in most. Two-thirds of mothers (67%) reported inconsistently feeling fetal movements. This pilot study contributed to the refinement of participant selection, identification of data source, expansion of data sets, and areas for future exploration prior to the implementation of a multisite AMC pediatric registry.

International multidisciplinary collaboration toward an annotated definition of arthrogryposis multiplex congenita.

Arthrogryposis multiplex congenita (AMC) has been described and defined in thousands of articles, but the terminology used has been inconsistent in clinical and research communities. A definition of AMC was recently developed using a modified Delphi consensus method involving 25 experts in the field of AMC from 8 countries. Participants included health care professionals, researchers, and individuals with AMC. An annotation of the definition provides more in-depth explanations of the different sentences of the AMC definition and is useful to complement the proposed definition. The aim of this study was to provide an annotation of the proposed consensus-based AMC definition. For the annotation process, 17 experts in AMC representing 10 disciplines across 7 countries participated. A paragraph was developed for each sentence of the definition using an iterative process involving multiple authors with varied and complementary expertise, ensuring all points of view were taken into consideration. The annotated definition provides an overview of the different topics related to AMC and is intended for all stakeholders, including youth and adults with AMC, their families, and clinicians and researchers, with the hopes of unifying the understanding of AMC in the international community.

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.

Genetics and Classifications.

Arthrogryposis multiplex congenital (AMC) is a descriptive term for a group of conditions that all share the characteristic of congenital contractures. There are an estimated 400 discrete diagnoses that can lead to a child being born with arthrogryposis. The 2 biggest categories of conditions are amyoplasia and distal arthrogryposis, which combined make up ∼50% to 65% of all diagnoses within the AMC subset. Amyoplasia, the most common AMC condition, seems to be a nongenetic syndrome, leading to very characteristic upper and lower limb contractures. The distal arthrogryposes, in contrast, have an underlying genetic abnormality, which in many cases seems to target the fast twitch muscles of the developing fetus. Classifying AMC is a difficult task, given the broad range of conditions represented. Four different classification schemes are presented.

Background to the 2nd International Symposium on Arthrogryposis.

Arthrogryposis multiplex congenital is a relatively uncommon condition, with little consensus on treatment. In 2007, the 1st International Symposium on Arthrogryposis was held in Birmingham, United Kingdom, to bring together patients, their families, and a multinational group of health care experts in the field of arthrogryposis, to discuss various aspects of the care of patients with arthrogryposis multiplex congenital. From that meeting, there was a coalescence of thought on diagnosis and classification, a sharing of practices on treatments and their outcomes, and an agreement on future directions. At the beginning of the 2nd International Symposium on Arthrogryposis held in Saint Petersburg in September 2014, Russia, these "lessons learnt" were synopsized to set the tone for the new meeting.

Treatment of Scoliosis Associated With Arthrogryposis Multiplex Congenita.

Scoliosis in children with arthrogryposis occurs in the minority of patients, but appears early, often present at birth. Curves can progress quickly. Treatment options include spine casting, bracing, expandable implant surgery, and spinal fusion. The goal is to allow as much chest growth and development as possible, along with a resulting well-balanced spine.

Anaesthesiology for Children With Arthrogryposis.

Patients with arthrogryposis often require anesthesia for surgical procedures. Intubation can be challenging due to lack of visualization. Anesthetic maintenance is fairly routine. Pheripheral blocks are an important adjunct to postoperative pain management.

Treatment of the Lower Extremity Contracture/Deformities.

Lower extremity deformities of patients with arthrogryposis multiplex congenita present a wide spectrum of severity and deformity combinations. Treatment goals range from merely ensuring comfortable seating and shoe wear, to fully independent and active ambulation, but the overarching intention is to help realize the patient's greatest potential for independence and function. Treatment of hip and knee contractures and dislocations has become more interventional, whereas treatment of foot deformities has paradoxically become much less surgical. This article synopsizes the treatment strategies presented in September 2014 in Saint Petersburg, Russia at the second international symposium on arthrogryposis.

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.

Summary of the 2nd International Symposium on Arthrogryposis, St. Petersburg, Russia, September 17-19, 2014.

Enormous progress has been made in understanding the etiology and therapies for arthrogryposis (multiple congenital contractures). A 2nd International Symposium on Arthrogryposis was sponsored by the Turner Institute in St. Petersburg, Russia. Olga Agranovich, Head of the Arthrogryposis Department of the Turner Institute, organized this special meeting. Care providers from multiple disciplines from all over the world representing 18 nations attended. Participants included: Pediatric orthopedic specialists, rehabilitation physicians, occupational therapists, physical therapists, medical geneticists, neurologists, craniofacial physicians, psychologists, developmental biologists, as well as representatives from parent support groups. The 1st symposium established the need for a collaborative and interdisciplinary approach to the treatment of arthrogryposis, engagement of parent support organizations, and the aim for more research. The Second Symposium highlighted the continuing need for more research on various therapies, identification of different types of arthrogryposis, standardized descriptions of severity, development of new orthotics, improved prenatal diagnosis, and studying adult outcome. Major progress has been made on both upper and lower limb treatments.

Achievement of gross motor milestones in children with idiopathic clubfoot treated with the Ponseti method.

BACKGROUND: The Ponseti method of idiopathic clubfoot treatment involves a series of weekly casts, a percutaneous Achilles tenotomy if needed, followed by wearing a foot abduction orthosis (FAO). Gross motor development of children with idiopathic clubfoot has not been examined. The purposes of this study were to determine the ages of achievement of gross motor milestones in children with clubfoot treated with Ponseti method and to compare those ages with historical normative developmental data. METHODS: In this prospective study, 51 children with idiopathic clubfoot who had their first cast applied when ≤90 days old, were full-term with no other orthopaedic conditions or previous clubfoot treatment, and were compliant with wearing FAO were enrolled. Parents were interviewed repeatedly to acquire the ages of achievement of 8 gross motor milestones. RESULTS: Fifteen children were excluded for reasons such as noncompliance with FAO, and not returning for follow-up. Thirty-six children, mean age of 15.2 days at first casting, achieved rolling prone to supine at a mean age of 5.1 months, rolling supine to prone at 5.1 months, sitting without support at 6.6 months, crawling on stomach at 7.1 months, crawling on hands and knees at 8.6 months, pull-to-stand at 9.0 months, cruising at 10.2 months, and ambulating independently at 13.9 months. When compared with previously published values for unaffected children, the mean ages of achievement for 6 of 8 milestones were significantly greater (P<0.05) for the children with clubfoot. The preambulatory milestones were achieved from 0.7 to 1.5 months later and independent ambulation up to 2.2 months later. Fifty percent of children with clubfoot were ambulating at 13.8 months; 90% at 17.7 months. CONCLUSIONS: Minimal delays in gross motor milestone achievement were found in children with idiopathic clubfoot treated with the Ponseti method. Delays were, at most, 1.5 months, except for independent ambulation, which was approximately 2 months. These findings should enable pediatric clinicians to alleviate the concerns of parents of children with idiopathic clubfoot regarding gross motor milestone achievement. LEVEL OF EVIDENCE: Therapeutic Level II.

Ponseti treatment for clubfeet: an international perspective.

PURPOSE OF REVIEW: The purpose of this article is to acquaint the reader with the Ponseti method of clubfoot treatment and to describe the features of the technique that make it superior to other forms of clubfoot treatment. These features make the technique applicable across a wide spectrum of healthcare delivery systems on a truly international basis. RECENT FINDINGS: The Ponseti method has proven to be successful around the globe, in both industrialized countries and developing nations. In many settings, nonphysician practitioners are primarily responsible for the casting phase of treatment, particularly in areas with a shortage of physicians. Internationally, researchers are effectively expanding the scope of clubfeet treated: older children, postsurgical recurrent deformities, and nonidiopathic clubfeet. The barriers that undermine the outcomes of a Ponseti clubfoot program are primarily poverty and noncompliance with the extended post-casting brace protocol. SUMMARY: The Ponseti method should be considered the best treatment modality for all children with clubfeet. In the developing world, where most neglected clubfeet occur, emphasis should continue to be the training of practitioners and implementation of programs to reach all affected children. Research will continue to broaden the indications for the method.

Pelvic positioning creates error in CT acetabular measurements.

BACKGROUND: CT allows for accurate measurement of acetabular orientation and shape, but malpositioning of the pelvis may lead to measurement variance. PURPOSE: We therefore sought to determine: (1) whether acetabular anteversion measurements using the femoral head centers differed from those using the posterior ischia, and (2) the extent to which changing obliquity, rotation, and tilt of a pelvis in a CT scanner affected the measurement of acetabular variables. METHODS: A radiopaque human pelvis model with articulated hips was suspended from a plastic sheet as part of an adjustable frame. Changes in the transverse and sagittal planes created rotation and tilt, while rotating the frame in the coronal plane created obliquity. CT scans were obtained, varying the combinations of obliquity, rotation, and tilt by intervals of 5°, up to 20°. Acetabular anteversion (AA), anterior acetabular sector angle (AASA), posterior acetabular sector angle (PASA), and horizontal acetabular sector angle (HASA) were measured. RESULTS: The two methods for measuring AA yielded values differing by 1° to 4° but correlated (r = 0.981) across the spectrum of pelvis positioning. Pelvic obliquity and tilt were linearly associated with changes in the measurements. For each 1°-increase in pelvic obliquity, AA changed -0.4°, and AASA, PASA, and HASA changed 1.93°, 0.99°, and 2.80°, respectively. For each 1°-increase in pelvic tilt, AA changed 0.8°, and AASA, PASA, and HASA changed -1.07°, 0.52°, and -0.51°, respectively. Rotation had no affect on the variables. CONCLUSIONS: Small changes in pelvic obliquity and tilt were associated with variances in acetabular measurements. The measured changes were directly proportional to the changes in obliquity and tilt, and were additive. Pelvic rotation created no changes in measurement.

A Genomic Approach to Delineating the Occurrence of Scoliosis in Arthrogryposis Multiplex Congenita.

Arthrogryposis multiplex congenita (AMC) describes a group of conditions characterized by the presence of non-progressive congenital contractures in multiple body areas. Scoliosis, defined as a coronal plane spine curvature of ≥10 degrees as measured radiographically, has been reported to occur in approximately 20% of children with AMC. To identify genes that are associated with both scoliosis as a clinical outcome and AMC, we first queried the DECIPHER database for copy number variations (CNVs). Upon query, we identified only two patients with both AMC and scoliosis (AMC-SC). The first patient contained CNVs in three genes (FBN2, MGF10, and PITX1), while the second case had a CNV in ZC4H2. Looking into small variants, using a combination of Human Phenotype Ontogeny and literature searching, 908 genes linked with scoliosis and 444 genes linked with AMC were identified. From these lists, 227 genes were associated with AMC-SC. Ingenuity Pathway Analysis (IPA) was performed on the final gene list to gain insight into the functional interactions of genes and various categories. To summarize, this group of genes encompasses a diverse group of cellular functions including transcription regulation, transmembrane receptor, growth factor, and ion channels. These results provide a focal point for further research using genomics and animal models to facilitate the identification of prognostic factors and therapeutic targets for AMC.