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: 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.

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.

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.

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.

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.

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.

Lessons Learned at the Epicenter of Brazil's Congenital Zika Epidemic: Evidence From 87 Confirmed Cases.

Congenital Zika virus infection has stimulated great international concern. A prospective case series of 87 infants with laboratory-confirmed congenital Zika syndrome (CZS) at the epicenter of the Brazilian Zika epidemic in Pernambuco state is presented. Mothers were interviewed for symptoms of possible Zika virus (ZIKV) infection during pregnancy, and fetal ultrasounds were obtained. Infant cerebrospinal fluid (CSF) samples were tested for ZIKV-specific antibodies, and sera were screened for other congenital infections. Neuroimaging and ophthalmologic evaluations were also performed. Sixty-six mothers (76%) reported symptoms of ZIKV infection during gestation. Fetal ultrasounds were available from 90% of the mothers, and all demonstrated brain structural abnormalities. All of the CSF samples tested positive for ZIKV immunoglobulin M. The majority of infants (89%) were term; the mean birth weight was 2577 ± 260 g, and the mean head circumference was 28.1 ± 1.8 cm. Severe microcephaly, defined as head circumference 3 SD below the mean for sex and gestational age, was found in 72 (82%) infants. All infants had an abnormal neurological exam, and 18 (20.7%) had arthrogryposis. The main abnormalities detected in computed tomography scans were calcifications (99%), followed by ventricular enlargement (94%), cortical hypogyration (81%), and less commonly, cerebellar hypoplasia (52%). Unilateral diaphragm paralysis was identified in 3 infants. Maternal young age, term infant, small for gestational age, and the presence of ophthalmologic abnormalities were significantly associated with a smaller head circumference Z score. Our findings, based on laboratory-confirmed ZIKV infection, add valuable evidence for the understanding of CZS.

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.

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.

Anesthetic Outcomes of Children With Arthrogryposis Syndromes: No Evidence of Hyperthermia.

BACKGROUND: Arthrogryposis syndromes are a heterogeneous group of disorders characterized by congenital joint contractures often requiring multiple surgeries during childhood to address skeletal and visceral abnormalities. Previous reports suggest that these children have increased perioperative risk, including hypermetabolic events discrete from malignant hyperthermia, difficult airway management, isolated hyperthermia, and difficult IV line placement. We sought to compare children with arthrogryposis multiplex congenita (AMC) versus the less severe, distal arthrogryposis syndromes (DAS) and to evaluate possible intraoperative hyperthermia of patients with AMC. We hypothesized that children with AMC had a greater incidence of intraoperative hyperthermia and more difficulty with airway management and IV access. METHODS: Children aged 0 to 25 years with arthrogryposis syndromes who underwent anesthesia from 1972 to 2013 were identified. The medical records were reviewed for demographics, arthrogryposis type, and anesthetic complications. AMC subjects were compared with DAS subjects. To evaluate the probability of hyperthermia and hypermetabolic responses of patients with AMC, we performed a post hoc case-control analysis. Patients with AMC were matched in a 1:2 ratio to patients without arthrogryposis to evaluate the primary outcome of maximum intraoperative temperature. RESULTS: Forty-five patients with AMC and 16 patients with DAS underwent 264 and 105 unique anesthetics, respectively. There was no significant difference in intraoperative hyperthermia or hypermetabolic events (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.36-2.47; P = .90). Children with AMC were more likely to have difficult IV access (OR, 7.1; 95% CI, 1.81-27.90; P = .005). Additional evidence suggested that difficult airway management (OR, 4.06; 95% CI, 1.01-16.39; P = .049) and hemodynamic instability (OR, 4.22; 95% CI, 1.03-17.26; P = .045) were more likely in children with AMC. From post hoc case-control analysis, there was no significant difference in the mean maximum intraoperative temperature (estimated difference +0.04°C; 95% CI, -0.14 to +0.22; P = .64) or odds of intraoperative hyperthermia (OR, 1.49; 95% CI, 0.78-2.82; P = .223) for patients with AMC compared with control subjects. CONCLUSIONS: Children with arthrogryposis syndromes present challenges to the anesthesia and surgical teams, including greater neuromuscular disease burden and challenging peripheral IV placement, with additional evidence suggesting difficult airway management and intraoperative hemodynamic instability. Although more definitive studies are warranted, we did not find evidence of increased odds of intraoperative hyperthermia or hypermetabolic responses.

Prevalence of Common Types of Compression Neuropathies in Qena Governorate/Egypt: A Population-Based Survey.

BACKGROUND: No epidemiological studies on the prevalence of compressive neuropathy have been undertaken in Arab countries. The aim of the study was to estimate the prevalence of the most common types of compressive neuropathies in Qena governorate/Egypt. METHODS: The study was part of a community-based survey carried out to assess the prevalence of neuromuscular disorders among the Qena population. A random sampling of 10 districts, 5,039 inhabitants aged ≥20. There were 3,050 urban residents (60.5%) and 1,989 (39.5%) from the rural community. Patients were diagnosed using a screening questionnaire for diagnosis of entrapment neuropathies. Positive cases were referred to the Qena University Hospital. They were given full clinical, electrophysiological and laboratory investigations. RESULTS: Compressive neuropathy was recorded in 165 cases giving a CPR = 3.3% of population at risk (≥20 years). Carpal tunnel syndrome (CTS) was diagnosed in 155 cases giving a CPR = 3.1% with a significantly higher prevalence among females than males (5.3 vs. 0.9%) and in rural compared with urban populations (4.6 vs. 2.1%). Ulnar neuropathy at the elbow was the second common type of entrapment with a CPR = 0.1% followed by radial nerve palsy, tarsal tunnel syndrome and common peroneal nerve palsy. CONCLUSION: The overall crude prevalence rate of CTS is comparable with that in other countries.

Arthrogryposis multiplex congenital - multidisciplinary care - including own experience.

Arthrogryposis multiplex congenital (AMC) is a heterogeneous disorder, characterized by nonprogressive multiple intra-articular contractures, which can be recognized at birth. The prevalence in Europe is estimated at about 1 per 12,000. Etiopathogenesis of arthrogryposis is multifactorial. Symptoms of some forms of arthrogryposis can be found in the clinical presentation of selected genetic disorders, e.g. Pena Shokeir syndrome. Arthrogryposis can also result from environmental factors such as medication, trauma or chronic illness during pregnancy, as well as from oligohydramnios or abnormal structure of the uterus. In this particular disorder prenatal diagnosis is crucial, because it determines the level of hospital reference during the delivery of the affected child. The highest reference degree hospital is preferential, with staff prepared for the multidisciplinary approach to the treatment of the newborn. The key to success is rehabilitation treatment and it should be initiated as soon as possible. In a substantial number of cases, physical therapy can replace invasive corrective surgery, but even when orthopedic treatment is required, it should always be preceded and followed by rehabilitation.

The LITAF/SIMPLE I92V sequence variant results in an earlier age of onset of CMT1A/HNPP diseases.

Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) represent the most common heritable neuromuscular disorders. Molecular diagnostics of CMT1A/HNPP diseases confirm clinical diagnosis, but their value is limited to the clinical course and prognosis. However, no biomarkers of CMT1A/HNPP have been identified. We decided to explore if the LITAF/SIMPLE gene shared a functional link to the PMP22 gene, whose duplication or deletion results in CMT1A and HNPP, respectively. By studying a large cohort of CMT1A/HNPP-affected patients, we found that the LITAF I92V sequence variant predisposes patients to an earlier age of onset of both the CMT1A and HNPP diseases. Using cell transfection experiments, we showed that the LITAF I92V sequence variant partially mislocalizes to the mitochondria in contrast to wild-type LITAF which localizes to the late endosome/lysosomes and is associated with a tendency for PMP22 to accumulate in the cells. Overall, this study shows that the I92V LITAF sequence variant would be a good candidate for a biomarker in the case of the CMT1A/HNPP disorders.

Amyoplasia revisited.

Amyoplasia is a specific type and the most common form of arthrogryposis (multiple congenital contractures). It is a clinical diagnosis at this time. Care should be used making the diagnosis because of the implications for recurrence, natural history, associated anomalies, and both etiology and pathogenesis. We reviewed over 600 published reports and 2,500 individual records to identify the 560 individuals reported here. Affected limbs had characteristic positions with fatty-fibrous replacement of muscle. Upper limb involvement was usually characterized by extended elbows. Lower limbs were held in various positions at birth; however, equinovarus positioning of feet was almost always present. Symmetric involvement was common. Among 560 affected individuals, subtypes were identified: four-limb symmetric involvement (331/560 = 55.9%), severe involvement (41/560 = 7.3%), three-limb involvement (27/560 = 4.8%), upper limb only Amyoplasia (ULA; 94/560 = 16.8%), and lower limb only Amyoplasia (LLA; 25/560 = 15.5%). Discordant monozygotic twinning was increased, occurring in 6.6% (37/560; OR 10.9). A variety of additional anomalies were seen, attributed to apparent vascular compromise. Gastrointestinal vascular compromise-type anomalies were present in 9.1% (51/560), trunk muscle defects in another 2.7% (15/560), digit compromise in 12.1% (68/560), constriction rings in 4.3% (24/560), and perinatal long bone fractures in 10.5% (59/560). Although prenatal ultrasound became the standard of care in 1990, only about one quarter of affected pregnancies were diagnosed prenatally since 1990. Amyoplasia appears to be completely sporadic. Novel pathogenetic mechanisms for the congenital anomalies seen in Amyoplasia need to be identified.

Delineation of the 3p14.1p13 microdeletion associated with syndromic distal limb contractures.

Distal limb contractures (DLC) represent a heterogeneous clinical and genetic condition. Overall, 20-25% of the DLC are caused by mutations in genes encoding the muscle contractile apparatus. Large interstitial deletions of the 3p have already been diagnosed by standard chromosomal analysis, but not associated with a specific phenotype. We report on four patients with syndromic DLC presenting with a de novo 3p14.1p13 microdeletion. The clinical features associated multiple contractures, feeding problems, developmental delay, and intellectual disability. Facial dysmorphism was constant with low-set posteriorly rotated ears and blepharophimosis. Review of previously reported cases with a precise mapping of the deletions, documented a 250 kb smallest region of overlap (SRO) necessary for DLC. This region contained one gene, EIF4E3, the first three exons of the FOXP1 gene, and an intronic enhancer of FOXP1 named hs1149. Sanger sequencing and locus quantification of hs1149, EIF4E3, and FOXP1 in a cohort of 11 French patients affected by DLC appeared normal. In conclusion, we delineate a new microdeletion syndrome involving the 3p14.1p13 locus and associated with DLC and severe developmental delay.

The efficacy of rib-based distraction with VEPTR in the treatment of early-onset scoliosis in patients with arthrogryposis.

BACKGROUND: Although arthrogryposis multiplex congenital (AMC) is a rare condition, rapidly progressive scoliosis is common in children with AMC. Only a limited number of studies characterize the nature of these curves, and even fewer describe surgical outcomes. To determine efficacy or rib-based distraction in these patients, we reviewed the outcomes of the use of the Vertical Expandable Prosthetic Titanium Rib (VEPTR) device in what we believe is the first study to report this. METHODS: Search of the Chest Wall Spinal Deformity Study Group database identified 10 children with AMC and early-onset scoliosis who were treated with the VEPTR device at 6 different pediatric health centers. The 7 female and 3 male patients had their initial surgery at an average age of 5 years. Mean follow-up was 4.2 years. RESULTS: The most common curve was from T5 to L2. After initial VEPTR insertion, the scoliosis decreased from a mean of 67 to 43 degrees (37% correction) and kyphosis from 65 to 48 degrees (29% correction). The mean proximal junctional kyphosis after initial insertion was 33 degrees. At final follow-up, scoliosis and kyphosis were 55 degrees (17% correction) and 62 degrees (8% correction), respectively. Spinal growth during the treatment period showed a mean T1-S1 increase of 4.2 cm or approximately 1 cm/y. In the 62 procedures performed over the course of the study period, 6 complications occurred in 4 patients: 3 infections, 2 rib failures, and 1 implant failure. Six patients had proximal junctional kyphosis of ≥45 degrees at the last follow-up. CONCLUSIONS: In children with AMC, rib-based distraction using the VEPTR is an effective treatment method for controlling scoliosis and kyphosis and maintaining thoracic growth, but proximal junctional kyphosis remains a problem.

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.

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.