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.

Arthrogryposis multiplex congenita: dental and maxillofacial phenotype - A scoping review.

INTRODUCTION: Arthrogryposis multiplex congenita (AMC) is a heterogeneous group of disorders associated with decreased fetal movement, with a prevalence between 1/3000 and 1/5200 live births. Typical features of AMC include multiple joint contractures present at birth, and can affect all joints of the body, from the jaw, and involving the upper limbs, lower limbs and spine. The jaws may be affected in 25 % of individuals with AMC, with limited jaw movement and mouth opening. Other oral and maxillofacial deformities may be present in AMC, including cleft palate, micrognathia, periodontitis and delayed teething. To our knowledge, oral and maxillofacial abnormalities have not been systematically assessed in individuals with AMC. Therefore, this scoping review was conducted to identify, collect, and describe a comprehensive map of the existing knowledge on dental and maxillofacial involvement in individuals with AMC. METHODOLOGY: A scoping review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. The PRISMA guidelines for scoping reviews were followed and databases were searched for empirical articles in English and French published until October 2022. We searched MEDLINE, Embase, Web of Science and ERIC databases. Two authors independently reviewed the articles and extracted the data. RESULTS: Of a total of 997 studies that were identified, 96 met the inclusion criteria and were subsequently included in this scoping review. These 96 studies collectively provided insights into 167 patients who exhibited some form of oral and/or maxillofacial involvement. Notably, 25 % of these patients were within the age range of 0-6 months. It is worth highlighting that only 22 out of the 96 studies (22.9 %), had the primary objective of evaluating dental and/or maxillofacial deformities. Among the patients studied, a prevalent pattern emerged, revealing that severe anomalies such as micrognathia (56 %), high-arched palate (29 %), cleft palate (40 %), limited mouth opening (31 %), and dental anomalies (28 %) were frequently observed. Importantly, many of these patients were found to have more than one of these anomalies. Even though these maxillofacial impairments are known to be associated with dental problems (e.g., cleft palate is associated with oligodontia, hypodontia, and malocclusion), their secondary effects on the dental phenotype were not reported in the studies. CONCLUSION: Our findings have uncovered a notable deficiency in existing literature concerning dental and maxillofacial manifestations in AMC. This underscores the need for interdisciplinary collaboration and the undertaking of extensive prospective cohort studies focused on AMC. These studies should assess the oral and maxillofacial abnormalities that can impact daily functioning and overall quality of life.

Epidemiology, aetiology, interventions and genomics in children with arthrogryposis multiplex congenita: protocol for a multisite registry.

INTRODUCTION: Arthrogryposis multiplex congenita (AMC) is an umbrella term including hundreds of conditions with the common clinical manifestation of multiple congenital contractures. AMC affects 1 in 3000 live births and is caused by lack of movement in utero. To understand the long-term needs of individuals diagnosed with a rare condition, it is essential to know the prevalence, aetiology and functional outcomes in a large sample. The development and implementation of a multicentre registry is critical to gather this data. This registry aims to improve health through genetic and outcomes research, and ultimately identify new therapeutic targets and diagnostics for treating children with AMC. METHODS AND ANALYSIS: Participants for the AMC registry will be recruited from seven orthopaedic hospitals in North America. Enrollment occurs in two phases; Part 1 focuses on epidemiology, aetiology and interventions. For this part, retrospective and cross-sectional data will be collected using a combination of patient-reported outcomes and clinical measures. Part 2 focuses on core subset of the study team, including a geneticist and bioinformatician, identifying causative genes and linking the phenotype to genotype via whole genome sequencing to identify genetic variants and correlating these findings with pedigree, photographs and clinical information. Descriptive analyses on the sample of 400 participants and logistic regression models to evaluate relationships between outcomes will be conducted. ETHICS AND DISSEMINATION: Ethical approval has been granted from corresponding governing bodies in North America. Dissemination of findings will occur via traditional platforms (conferences, manuscripts) for the scientific community. Other modalities will be employed to ensure that all stakeholders, including youth, families and patient support groups, may be provided with findings derived from the registry. Ensuring the findings are circulated to a maximum amount of interested parties will ensure that the registry can continue to serve as a platform for hypothesis-driven research and further advancement for AMC.

Test-retest reliability for performance-based outcome measures among individuals with arthrogryposis multiplex congenita.

BACKGROUND: Most individuals with arthrogryposis multiplex congenita, a rare condition characterized by joint contractures in ≥ 2 body regions, have foot and ankle involvement leading to compromised gait and balance. The purpose of this study was to establish between-days, test-retest reliability for performance-based outcome measures evaluating gait and balance, i.e., the 10-m Walk Test, Figure-of-8 Walk Test, 360-degree Turn Test, and modified Four Square Step Test, among adolescents and adults with arthrogryposis multiplex congenita. METHODS: This reliability study included ambulatory participants, aged 10 to 50 years, with a medical diagnosis of arthrogryposis multiplex congenita. Participants completed performance-based measures, in a randomized order, on two separate occasions. Intraclass correlation coefficients with 95% confidence intervals and minimal detectable changes at the 90% and 95% confidence level were calculated. RESULTS: Participants included 38 community-ambulators with a median of 13 out of 14 upper and lower joint regions affected. Intraclass correlation coefficient point estimates and 95% confidence intervals ranged from .85-.97 and .70-.98, respectively. Minimal detectable changes were 10 to 39% of sample means and were largest for the modified Four Square Step Test. CONCLUSIONS: Among individuals with arthrogryposis, gait speed per the 10-m Walk Test, as well as non-linear walking and dynamic balance assessment per the Figure-of-8 Walk and 360 Degree Turn Tests, have adequate test-retest reliability enabling evaluation of individual patient changes. Changes in groups of ambulatory individuals with arthrogryposis multiplex congenita may be reliably evaluated with all of the studied outcome measures.

Arthrogryposis multiplex congenita: a 28-year retrospective study.

AIM: To identify all patients with arthrogryposis multiplex congenita presenting to a specialized pediatric orthopedic institution over a 28-year period; classify them into three groups (general arthrogryposis not otherwise specified [NOS], amyoplasia, or distal arthrogryposis); report the frequency of various musculoskeletal features; and determine the rate of operative treatment. METHOD: Patients with arthrogryposis under the age of 18 years who presented between 1990 and 2017 were included. Patients were placed into one of three groups based on clinical features and family history when available. Age of presentation, joint involvement, and utilization of surgical treatment were recorded. RESULTS: There were 417 patients in total (184 females, 233 males); 235 patients (56.4%) had general arthrogryposis NOS, 107 (25.7%) had amyoplasia, and 75 (18.0%) had distal arthrogryposis. Patients with amyoplasia presented at a younger age (median 4mo) than those with general arthrogryposis NOS (median 1y 3mo, p=0.005), and had a lower rate of spine involvement than patients with general arthrogryposis NOS (p=0.004) and distal arthrogryposis (p=0.023). The average number of surgeries across all patients was 1.9 (SD 2.2). INTERPRETATION: Pediatric patients with amyoplasia present to orthopedic care earlier and are less likely to have spine involvement than other forms of arthrogryposis. Multiple surgeries are common among all patients with arthrogryposis.

The mystery of monozygotic twinning II: What can monozygotic twinning tell us about Amyoplasia from a review of the various mechanisms and types of monozygotic twinning?

Monozygotic (MZ) twins ("identical twins") are essentially unique to human beings. Why and how they arise is not known. This article reviews the possible different types of MZ twinning recognized in the previous article on twins and arthrogryposis. There appear to be at least three subgroups of MZ twinning: spontaneous, familial, and those related to artificial reproductive technologies. Each is likely to have different etiologies and different secondary findings. Spontaneous MZ twinning may relate to "overripe ova." Amyoplasia, a specific nongenetic form of arthrogryposis, appears to occur in spontaneous MZ twinning and may be related to twin-twin transfusion.

Quality of life in hereditary neuropathy with liability to pressure palsies is as impaired as in Charcot-Marie-Tooth disease type 1A.

To date, only one study assessed quality of life (QoL) in patients with hereditary neuropathy with liability to pressure palsies (HNPP). We aimed to fill in this gap by investigating QoL in a cohort of patients with HNPP compared to Charcot-Marie-Tooth type 1A (CMT1A) patients, as well as to analyze sociodemographic and clinical features associated with QoL in HNPP. Eighteen genetically confirmed HNPP patients were age-and gender-matched with 18 CMT1A patients. SF-36 questionnaire was used to assess QoL. Medical Research Council (MRC) Sum Score, CMT Neuropathy Score (CMTNS), Overall Neuropathy Limitation Scale Score (ONLS), Falls Efficacy Score (FES), Visual Analog Pain Scale, Beck Depression Inventory (BDI) and Fatigue Severity Scale (FSS) were also used in our study. Although HNPP patients were less clinically impaired, no difference was observed in these two cohorts regarding SF-36 scores. Worse QoL in HNPP patients was associated with lower education (p < 0.01), physical work (p < 0.05), higher number of clinically affected nerves during the disease course (p < 0.01), worse MRC-SS score (p < 0.01), worse ONLS score (p < 0.01), and with more severe pain (p < 0.01), depression (p < 0.01), and fatigue (p < 0.01). Worse pain at the moment of testing appeared as a significant independent predictor of worse QoL in HNPP patients (ß = - 0.93, p < 0.001). QoL was similarly impaired in patients with HNPP and patients with CMT1A. We identified different factors associated with QoL in HNPP, and many of these factors are amenable to treatment which is of special interest in these still incurable disease.

Association Between Arthrogryposis and Mortality in Infants With Congenital Zika Syndrome: A Systematic Review and Meta-analysis.

BACKGROUND: Intrauterine Zika virus infection is associated with neurological disorders and other problems, including such as impaired visual and hearing function and orthopedic abnormalities, including arthrogryposis. We systematically investigated the prevalence of arthrogryposis in infants with congenital Zika syndrome and the respective risk of mortality. METHODS: We conducted a systematic review and meta-analysis of reports published in PubMed, Web of Science, SCOPUS, and World Health Organization Global Index Medicus databases, using the keywords Zika virus and arthrogryposis and related terms. RESULTS: After screening titles and abstracts, a total of four studies were included. Arthrogryposis was not associated with increased risk for fetal demise (risk ratio, 3.33; 95% confidence interval, 0.73 to 15.26). However, arthrogryposis was associated with a 13-fold increased risk of mortality in neonates with congenital Zika syndrome (risk ratio, 13.11; 95% confidence interval, 3.74 to 45.92) than neonates with congenital Zika syndrome but without arthrogryposis. CONCLUSIONS: Neonates with both congenital Zika syndrome and arthrogryposis had higher morbidity and mortality risks, making it necessary to implement protocols for the early identification of neuromuscular changes and appropriate management of patients.

Patient-reported Outcomes in Arthrogryposis.

BACKGROUND: Little is known about patient-reported health status in children and adolescents with arthrogryposis. Utilizing the Patient-Reported Outcome Measurement Information System (PROMIS) and Pediatric Outcomes Data Collection Instrument (PODCI) questionnaires, we investigated functional and psychosocial measures in arthrogryposis. METHODS: A total of 118 patients with arthrogryposis were identified from a prospective longitudinal cohort (the Congenital Upper Limb Difference Registry) from 2014 to 2018. Demographics and patient-reported outcome measures were evaluated, including the PROMIS [upper extremity (UE) function, pain, depression, anxiety, and peer relations] and PODCI questionnaires (UE function, pain, happiness, and global function). RESULTS: A total of 29 arthrogrypotic patients had complete PROMIS and PODCI data. This cohort was divided into distal arthrogryposis and amyoplasia groups, with 15 and 14 patients in each group, respectively. There were 8 males in the distal arthrogryposis group with a median age of 9 years and 7 males in the amyoplasia group with a median age of 8 years. For both cohorts, the median UE function PROMIS scores were significantly below population norms, 31 for distal arthrogryposis and 22 for amyoplasia. PODCI UE function was statistically lower for amyoplasia compared with the distal arthrogryposis cohort. PROMIS pain, depression, anxiety, and peer relations were in the normal range for both amyopasia and distal arthrogryposis. Median PODCI pain and happiness ranged from 85 to 88 for all patients with no statistical difference between groups. CONCLUSIONS: Arthrogryposis patients have lower UE function scores compared with population normals, but they have emotional states that are consistent with populations norms. Amyoplasia patients were functionally worse than distal arthrogryposis patients. LEVELS OF EVIDENCE: Level II.

Comparison of clinical and electrophysiological features of patients with hereditary neuropathy with liability to pressure palsies with or without pain.

BACKGROUND: Hereditary neuropathy with liability to pressure palsies (HNPP) is a rare neuropathy with a heterogeneous clinical profile. Painless recurrent palsies are the usual presentation, but neuropathic pain could be predominant or inaugural. Browsing the medical literature, we only found two articles reffering to this important clinical feature. Whether there are differences between patients with or without pain is unclear. The main objective of this study was to compare the clinical and electrophysiological features of these patients and to evaluate the impact on their disability. METHODS: All patients diagnosed with HNPP at the Limoges University Hospital Centre were included and separated into two groups according to the presence or absence of neuropathic pain. In each case, the clinical, genetic, electrodiagnostic, therapeutic features and the modified Rankin Scale (mRS) were evaluated. RESULTS: Out of 23 patients, 52% presented with neuropathic pain. There was no difference between groups regarding to clinical and electrophysiological features, except for the amplitude of the ulnar sensory nerve (p < 0,003). The amplitudes of sensory nerve action potentials (SNAPs) seemed to be higher in patients with pain, but were below the lower limit of normal. Patients with pain had a higher mRS than patients without pain (p < 0,007). CONCLUSION: This study supports previous published results and highlights a trend for higher sensory amplitudes in HNPP patients with pain. We found a prevalence of neuropathic pain of 52% in patients with HNPP, underlining the need to systematically assess pain in such patients in order to improve their management.

Development of an online registry for adults with arthrogryposis multiplex congenita: A protocol paper.

Arthrogryposis multiplex congenita (AMC) is considered a rare disorder resulting in multiple congenital contractures in two or more areas. Considerable literature is available on managing the contractures during an affected child's development but little information is available to those managing these ongoing issues in adulthood. Due to the heterogeneity etiological factors and presentation of AMC, and the small sample sizes of previous studies, it has been difficult to generalize results to the adult population. This current study presents the several steps taken to create an international AMC database for adults to populate with their own data over time. The methods included a scoping review of the literature for valid and reliable outcome measures used for AMC, a Delphi methodology to create the database with a team of clinicians, researchers and patients, a Beta testing of the database, and a final launch of the Adult AMC Registry. This registry includes 48 nonstandardized questions and 12 standardized questionnaires. It takes 35-45 min for a participant to complete. A shorter version will be created for participants to complete for years 2 and 3, followed by this longer version every 4 years. The protocol for referring English-speaking patients and access to the registry is provided. Data will be reviewed every year to ensure quality. The registry will be maintained for a minimum of 10 years and data will be comprehensively analyzed every 5 years. Our goal is to have 500 adults with AMC from around the world as participants.

Arthrogryposis multiplex congenita in utero: radiologic and pathologic findings.

Arthrogryposis multiplex congenita (AMC) refers to the development of multiple joint contractures affecting two or more areas of the body prior to birth. It affects approximately 1 in 3000 individuals, mostly reported in individuals of Asian, African and European descent with equal incidence in males and females. Arthrogryposis is associated with over 400 medical conditions and 350 known genes with considerable variability in phenotypic expression. The primary underlying mechanism is decreased fetal movement during development. Prenatal imaging is crucial in early diagnosis by identifying fetal movement limitations and the presence of club foot or joint contractures. Postnatal autopsy confirms the diagnosis and extent of associated congenital anomalies and provides a valuable source of DNA material. Molecular methods are particularly useful in delineating novel gene mutations, locus heterogeneity and phenotype genotype correlation. Prenatal evaluation with early diagnosis via image scanning and further genetic surveillance give the opportunity for family counseling concerning future pregnancy management and expected neonatal morbidity and mortality.

Disability in adults with arthrogryposis is severe, partly invisible, and varies by genotype.

OBJECTIVE: To understand the disability of adults with arthrogryposis multiplex congenita (AMC), a rare disease spectrum characterized by at least 2 joint contractures at birth in different body areas. METHODS: This is a retrospective analysis of data for unselected persons with AMC referred to the French center for adults with AMC from 2010 to 2016. All underwent a pluriprofessional systematic and comprehensive investigation of deficits, activity limitation, and participation restriction according to the International Classification of Functioning, Disability and Health and genetic analysis when indicated. Participants were divided by amyoplasia and other AMC types. RESULTS: Mean (SD) age of the 43 participants (27 female) was 33.2 (13.4) years; 28 had amyoplasia and 15 other types of AMC. Beyond joint stiffness, deformities, and muscle weakness, the well-known core symptoms that we quantified and for which first-line treatment involved technical aids, other less visible disorders that could contribute to severe participation restriction were particularly pain and psychological problems including anxiety, fatigue, difficulty in sexual life, altered self-esteem, and feelings of solitude. Severe respiratory disorders were infrequent and were linked to PIEZO2 mutations. Gait disorders were not due to respiratory impairment but to skeletal problems and were always associated with amyoplasia when severe. Functional independence was worse but respiratory and swallowing capacities were better with amyoplasia than other AMC types. CONCLUSION: This study describes disability patterns of a cohort of adults with AMC by genotype. The disability of adults with AMC is influenced by genotype, with important invisible disability.

Frequency of hereditary neuropathy with liability to pressure palsies (HNPP) due to 17p11.2 deletion in a Korean newborn population.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder mainly due to a deletion of chromosome 17p11.2 including PMP22 (PMP22 Del HNPP). The prevalence of HNPP is estimated to be 0.84 to 16 per 100,000, but could be underestimated because of the mild symptoms of HNPP. In this study, we estimated the prevalence of PMP22 Del HNPP in a Korean newborn population who underwent next-generation sequencing (NGS)-based copy number variation (CNV) analysis. Of the 11,885 newborns tested by NGS-based CNV analysis, 17p11.2 deletions were found in seven samples. The prevalence of PMP22 Del HNPP was estimated to be 58.9 per 100,000 (95% confidence interval (CI), 25.8-116.5) or 1 in 1698 (95% CI, 1/909-1/5000). Our data suggest that PMP22 Del HNPP might not be uncommon at least in the Korean population.

Risk Factors of Impaired Pulmonary Function in Arthrogryposis Multiplex Congenital Patients With Concomitant Scoliosis: A Comparison With Adolescent Idiopathic Scoliosis.

STUDY DESIGN: A retrospective study. OBJECTIVE: To investigate the severity of pulmonary function impairment for arthrogryposis multiplex congenital (AMC) patients with concomitant scoliosis and to determine risk factors associated with the impaired pulmonary function in these patients. SUMMARY OF BACKGROUND DATA: AMC patients are generally believed to have impaired pulmonary function. However, the severity of respiratory morbidity and the associated risk factors have not been reported. METHODS: The pulmonary function tests data including the percentage predicted values of forced vital capacity (%FVC), forced expiratory volume in 1 second (%FEV1), and the ratio of FEV1 to FVC (%FEV1/FVC) were reviewed and compared for 48 AMC patients with secondary scoliosis and 48 patients with adolescent idiopathic scoliosis. The radiographic parameters of coronal and sagittal plane deformities and body mass index (BMI) were measured and correlated with impaired pulmonary function in these AMC patients. RESULTS: AMC patients with concomitant scoliosis had significant lower mean %FVC, %FEV1, and %FEV1/FVC than adolescent idiopathic scoliosis patients (48.8 vs. 70.3 for %FVC, P < 0.001; 45.3 vs. 69.7 for %FEV1, P < 0.001; 92.1 vs. 96.9 for %FEV1/FVC, P < 0.05, respectively). Seventy percent of AMC patients had severe pulmonary function impairment. A positive correlation was found between BMI and %FVC and %FEV1 (P < 0.01) and between hypokyphosis and %FVC and %FEV1 (P < 0.05). A negative correlation was found between coronal angle and pulmonary function (P < 0.05). Multiple regression analysis showed that all of the three variables were independent predictors associated with a reduced pulmonary function. With a combination of these variables, the multiple regression model could account for 38.7% of the variance in %FVC and 41.5% in %FEV1. CONCLUSION: There exists severe impairment of pulmonary function in AMC patients with concomitant scoliosis. The scoliotic curve, hypokyphosis, and BMI were independent risk factors associated with the pulmonary dysfunction in these patients. As the majority of the variability of impaired pulmonary function tests are still poorly understood, more risk factors await to be uncovered in future studies. LEVEL OF EVIDENCE: 4.

Does Reoperation Risk Vary for Different Types of Pediatric Scoliosis?

STUDY DESIGN: Retrospective cohort study of spine fusion surgery utilizing the New York State Inpatient Database. OBJECTIVE: The objective was to determine whether there were differences in reoperation rates among pediatric scoliosis associated with various etiologies compared with idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: The incidence of postoperative complications and reoperations is known to vary among patients with diverse scoliosis pathologies. As these are heterogeneous conditions and often with rare occurrence, it is difficult to compare them in a single study. We aimed to assess reoperation events after fusion for several etiologies of pediatric scoliosis. METHODS: The 2008 to 2011 New York State Inpatient Database was queried using International Classification of Diseases (ICD-9-CM) codes for patients with in-hospital stays including a spine arthrodesis for scoliosis. All approaches, all fusion lengths, and ages 10 to 21 were included. Patient identifiers and linkage variables were used to identify revisits. The relative risk of reoperation was calculated for several rare conditions associated with scoliosis. RESULTS: Two thousand three hundred fifty-six pediatric scoliosis fusion surgeries were identified in 2008 in the state of New York. The 1- and 4-year reoperation rate for idiopathic scoliosis was 0.9% and 1.6%, respectively. For nonidiopathic scoliosis, the 1- and 4-year rates were 4.2% and 20.4%, respectively. Of the nonidiopathic scoliosis subtypes, congenital scoliosis (4.7% risk at 1 y, 41.6% at 4 y), the neuromuscular disease arthrogryposis (7.3% risk at 1 y, 28.6% at 4 y), and syndrome neurofibromatosis (9.1% at 1 y, 32.3% at 4 y) showed the highest risk for reoperation. Length of stay and hospital charges were higher for reoperations. CONCLUSIONS: Using a large administrative database, we identified neuromuscular, syndromic, and congenital forms of scoliosis that have the highest relative risk for a reoperation within 1 year. At-risk populations should be identified and resources allocated and preventative measures instituted accordingly to prevent these costly events. LEVEL OF EVIDENCE: Level III.

Characterisation of pain in people with hereditary neuropathy with liability to pressure palsy.

Hereditary neuropathy with liability to pressure palsy (HNPP) has historically been considered a pain-free condition, though some people with HNPP also complain of pain. This study characterised persistent pain in people with HNPP. Participants provided cross-sectional demographic data, information on the presence of neurological and persistent pain symptoms, and the degree to which these interfered with daily life. The painDETECT and Central Sensitization Inventory questionnaires were used to indicate potential neuropathic, central sensitisation and musculoskeletal (nociceptive) pain mechanisms. Additionally, participants were asked if they thought that pain was related to/part of HNPP. 32/43 (74%) subjects with HNPP had persistent pain and experience this pain in the last week. Of those with pain, 24 (75%) were likely to have neuropathic pain and 27 (84%) were likely to have central sensitisation. All 32 participants felt that their pain could be related to/part of their HNPP. Significant negative impact of the pain was common. Pain characterisation identified neuropathic pain and/or central sensitisation as common, potential underlying processes. Pain may plausibly be directly related to the underlying pathophysiology of HNPP. Further consideration of including pain as a primary symptom of HNPP is warranted.

Congenital Malformations of Calves Infected with Shamonda Virus, Southern Japan.

In 2015 and 2016, we observed 15 malformed calves that were exposed to intrauterine infection with Shamonda virus, a Simbu serogroup orthobunyavirus, in Japan. Characteristic manifestations were arthrogryposis and gross lesions in the central nervous system. Our results indicate that this arbovirus should be considered a teratogenic virus in ruminants.

Evidence of extensive renewed Schmallenberg virus circulation in Belgium during summer of 2016 - increase in arthrogryposis-hydranencephaly cases expected.

A seroprevalence study carried out between June and September 2016 in the Belgian sheep population showed a significant increase in overall (from 25% to 62%) and between-herd (from 60% to 96%) seroprevalence against Schmallenberg virus (SBV) during this period, indicating the most extensive recirculation of SBV since its original emergence in 2011. SBV recirculation was confirmed by the detection of SBV RNA-positive Culicoides obsoletus complex midges collected in the region of Antwerp in August 2016, reaching a minimum infection rate of 3%. The recirculation of SBV in the largely unprotected ruminant population during summer 2016 will likely cause an increase in the number of arthrogryposis-hydranencephaly cases in newborn ruminants during the coming months.

Long-term functional and mobility outcomes for individuals with arthrogryposis multiplex congenita.

Arthrogryposis multiplex congenita (AMC) is a birth defect that involves congenital joint contractures in two or more joints including the limbs, spine, and jaw. The purpose of our study was to identify long-term outcomes of adults with AMC. We recruited 177 participants from over 15 countries, making this the largest international study of adults with AMC. Participants provided demographic information including living situation and mobility and completed two standardized outcome measures, of quality of life and physical activity, using an online survey format. The data were compiled and descriptive analyses were performed. The study group consisted of 72% females and a mean age of 39 years. Over 90% of participants had upper and lower limb involvement, 35% had scoliosis or lordosis while 16% had jaw problems. Participants had an average of nine (0-70) surgeries at the time of the study. The majority (75%) of respondents lived independently of family members (on their own or with a partner). Participants were nearly three times more likely to have a graduate degree than the general US population. Participants reported lower physical function scores than the general US population; however, they reported similar or higher scores for the other quality of life domains of the SF-36. They were considerably less physically active than able-bodied individuals. Half of participants experienced chronic back pain and 60% reported joint pain. Additionally, almost half of the participants took regular pain medications.