Intrafamilial Variability of the R694C Variant in BICD2 Presenting with Lethal Severe Arthrogryposis

Arthrogryposis multiplex congenita (AMC) is a heterogeneous condition comprising congenital multiple joint contractures, and it is secondary to decreased fetal mobility following environmental/genetic abnormalities. BICD2 pathogenic variants have been associated with autosomal dominant spinal muscular atrophy with lower extremity predominance (SMALED2). We report the case of a newborn with decreased fetal movements and ventriculomegaly diagnosed in utero, born with severe AMC, multiple bone fractures, congenital hip dislocation, and respiratory insufficiency that led to neonatal death. His mother had AMC diagnosis without established etiology. Her phenotype characterization was key to guide the genetic investigation. A BICD 2 heterozygous variant (NM_001003800.1; c.2080C > T; p. [Arg694Cys]) was detected both in the mother and the newborn. This variant had previously been reported in 3 cases, all having de novo severe SMALED-type 2B (MIM#618291) phenotype. This is the first report of this variant (p. [Arg694Cys]) presenting with an inherited, severe, and lethal phenotype associated to intrafamilial variability, suggesting a more complex phenotype-genotype correlation than previously stated.

Rare health conditions 54: arthrogryposis multiplex congenita, Edwards syndrome, and offering spiritual support

The purpose of this series is to highlight a range of rare health conditions. Rare health conditions are those that affect no more and usually fewer than 1 person in every 2000 and many HCAs and nurses will encounter some of these conditions, given the high number of them. This 54th article will examine two of these conditions, arthrogryposis multiplex congenita and Edwards syndrome, along with an exploration of the idea of support staff offering spiritual support to those with rare health conditions and their families.

Speech development in children of preschool age with arthrogryposis multiplex congenital with upper limb deformities

BACKGROUND: The difficulties or gross disturbance in motor development, which are diagnosed in children at an early age, are one of the prognostic markers of further problems in their speech development. AIM: This study aimed to determine the speech development of children with arthrogryposis multiplex congenita with upper limb deformities. MATERIALS AND METHODS: Speech examination was conducted in 21 children with arthrogryposis multiplex congenita preschool age (average age: 5.16 1.49 years) from 2020 to 2021. Patients were divided into 2 groups: group 1 (10 people) with children of younger and middle preschool age (average age 3.81 0.63 years) and group 2 (11 people) with children of older and preparatory preschool age (average age 6.39 0.78 years). The speech examination results were exposed to statistical analysis. RESULTS: The majority of children with arthrogryposis multiplex congenita had speech pathology (90.5%), whereas general speech underdevelopment dominated over speech development delay (78.9% and 21.1%, respectively). A high frequency of perinatal hypoxic-ischemic encephalopathy in children with arthrogryposis multiplex congenita (80.9%), a complicated perinatal anamnesis (57.1%), and a delay in early motor or speech development (100% and 52.4%, respectively) links with speech disorder development in the future. Patients with arthrogryposis have a large percentage of congenital pathology of the articulatory apparatus structure (57.1%). Of the children, 76.2% were with a total form of arthrogryposis multiplex congenita, whereas 23.8% with an isolated upper extremity lesion. No statistically significant differences were determined in the form of speech pathology between patients with various forms of arthrogryposis multiplex congenita. Children of the first age group had speech disorders in 90% of cases, whereas 90.9% in group 2. Based on the form of speech pathology, patients with general speech underdevelopment and speech development delay were determined in group 1 (55.6% and 44.4%, respectively), whereas children with general speech underdevelopment in group 2 (100%). In the clinical form of speech pathology, dysarthria prevailed in children of both age groups (80%). CONCLUSIONS: Children with arthrogryposis multiplex congenita with upper limb deformities have a high incidence of speech disorders. Early speech examination and speech therapy eliminated all detected disturbances.

Diagnostic workup in children with arthrogryposis: description of practices from a single reference centre, comparison with literature and suggestion of recommendations

IntroductionArthrogryposis multiplex congenita (AMC) refers to a clinical presentation of congenital contractures involving two or more body areas. More than 400 distinct conditions may lead to AMC, making the aetiological diagnosis challenging. The objective of this work was to set up evidence-based recommendations for the diagnosis of AMC by taking advantage of both data from our nation-wide cohort of children with AMC and from the literature.Material and methodsWe conducted a retrospective single-centre observational study. Patients had been evaluated at least once at a paediatric age in the AMC clinic of Grenoble University Hospital between 2007 and 2019. After gathering data about their diagnostic procedure, a literature review was performed for each paraclinical investigation to discuss their relevance.ResultsOne hundred and twenty-five patients were included, 43% had Amyoplasia, 27% had distal arthrogryposis and 30% had other forms. A definitive aetiological diagnosis was available for 66% of cases. We recommend a two-time diagnostic process: first, non-invasive investigations that aim at classifying patients into one of the three groups, and second, selected investigations targeting a subset of patients.ConclusionThe aetiological management for patients with AMC remains arduous. This process will be facilitated by the increasing use of next-generation sequencing combined with detailed phenotyping. Invasive investigations should be avoided because of their limited yield.

Psychosocial wellbeing among children and adults with arthrogryposis: a scoping review

Background Arthrogryposis multiplex congenita (AMC) is a group of congenital conditions characterized by joint contractures in two or more body areas. Management of AMC starts early in life and focuses on improving mobility and function through intensive rehabilitation and surgical interventions. Psychosocial wellbeing is an important determinant of health and the psychosocial experience of individuals with AMC should be considered in the management of this condition. The aim of this scoping review was to explore what is known about the psychosocial wellbeing of children and adults with AMC, to identify the outcome measures used and to explore the factors associated with psychosocial outcomes in this population. Methods A comprehensive search in four databases was conducted. Articles discussing psychosocial outcomes and outcome measures used with children or adults with AMC were included. Data on the measures used, psychosocial outcomes, and factors associated with psychosocial outcomes, were extracted and analyzed descriptively and synthesized narratively. Results Seventeen articles were included in this scoping review, ten including the pediatric population, six including adults and one article including both children and adults with AMC. The most commonly used outcome measures were the PODCI in the pediatric studies, and the SF-36 in studies on adults. In the pediatric studies, psychosocial outcomes were often secondary, compared to the studies on adults. Results showed that in both children and adults, psychosocial outcomes are comparable with the levels of the general population. Qualitative studies reflected the affective needs of this population and issues with emotional wellbeing. Factors such as fatigue and pain were associated with poorer psychosocial outcomes in adults with an impact on social relationships, intimacy and family planning. Conclusion Validated outcome measures, qualitative approaches and longitudinal studies are needed to better understand the psychosocial outcomes in AMC over time. Psychosocial support should be part of the multidisciplinary management of AMC throughout the lifespan.

First Report of SYNE1 Arthrogryposis Multiplex Congenita From Saudi Arabia With a Novel Mutation: A Case Report

Introduction: Arthrogryposis multiplex congenita (AMC), is a rare congenital condition characterized by multiple joint contractures often affecting both arms and legs which start prior to birth.Patient concern: The pediatrician attending delivery noticed the baby being dysmorphic with generalized hypotonia and multiple joint contractures at birth with antenatal history of reduced fetal movement. The patient was admitted to the neonatal intensive care unit for strict observation and further work up.Diagnosis: Whole Exome Sequencing was performed and identified the novel homozygous variant in the synaptic nuclear envelope protein1 [SYNE1] gene.Intervention: Multidisciplinary team were involved in the management plan, supportive care was the mainstay of treatment.Outcomes: Due to feeding difficulties and on and off requirement of oxygen support, the patient remained hospitalized for a long period then was discharged home on supplemental oxygen and gastrostomy tube feeding.Conclusions: AMC3 should be suspected in patients with decreased fetal movements, dysmorphic features, hypotonia, and arthrogryposis. Molecular testing of the SYNE1 gene confirms diagnosis.

Care pathway for fetal joint contractures, Fetal Akinesia Deformation Sequence and Arthrogryposis Multiplex Congenita.

Introduction The majority of arthrogryposis multiplex congenita (AMC) and lethal forms of AMC such as fetal akinesia deformation sequence (FADS) cases are missed prenatally. We have demonstrated the additional value of fetal motor assessment and evaluation in a multidisciplinary team for the period 2007-2016. An applied care pathway for fetuses presenting with joint contracture(s) in one anatomic region (e.g. talipes equinovares), more than one body part with non-progressive contractures and motility (AMC) and with deterioration over time (FADS). Methods The multidisciplinary team of Amsterdam University Medical Centre Expertise Centre FADS and AMC developed the care pathway. Additional tools are provided including a motor assessment by ultrasound examination and postmortem assessment form. Results An eight-step care pathway is presented with a proposed timing for prenatal sonographic examination, genetic examinations, multidisciplinary meetings, prenatal and postnatal counselling of the parents by specialist also treating after birth, follow-up of prenatal and postnatal findings with counselling for future pregnancies. Discussion/conclusion The scheduled serial structural and motor sonograpahic assessment together with follow-up examinations and genetic analysis, should be tailored per prenatal centre per available resources. The multidisciplinary care pathway may pave the way to increase detection rate and diagnosis of isolated contracture(s), talipes equinovares with underlying genetic causes and the rare phenotypes AMC/FADS and prompt treatment after birth within expertise teams.