Arthrogryposis is a clinical finding that is present either as a feature of a neuromuscular condition or as part of a systemic disease in over 400 Mendelian conditions. The underlying molecular etiology remains largely unknown because of genetic and phenotypic heterogeneity. We applied exome sequencing (ES) in a cohort of 89 families with the clinical sign of arthrogryposis. Additional molecular techniques including array comparative genomic hybridization (aCGH) and Droplet Digital PCR (ddPCR) were performed on individuals who were found to have pathogenic copy number variants (CNVs) and mosaicism, respectively. A molecular diagnosis was established in 65.2% (58/89) of families. Eleven out of 58 families (19.0%) showed evidence for potential involvement of pathogenic variation at more than one locus, probably driven by absence of heterozygosity (AOH) burden due to identity-by-descent (IBD). RYR3, MYOM2, ERGIC1, SPTBN4, and ABCA7 represent genes, identified in two or more families, for which mutations are probably causative for arthrogryposis. We also provide evidence for the involvement of CNVs in the etiology of arthrogryposis and for the idea that both mono-allelic and bi-allelic variants in the same gene cause either similar or distinct syndromes. We were able to identify the molecular etiology in nine out of 20 families who underwent reanalysis. In summary, our data from family-based ES further delineate the molecular etiology of arthrogryposis, yielded several candidate disease-associated genes, and provide evidence for mutational burden in a biological pathway or network. Our study also highlights the importance of reanalysis of individuals with unsolved diagnoses in conjunction with sequencing extended family members.

Our results show that the Ponseti technique is reproducible and effective in children at least up to 12 months of age. It can also produce good correction in children presenting with complex idiopathic deformities. Therefore, extensive joint releases should not be considered immediately in such cases. The treating surgeon should be meticulous in using the technique and ensure compliance to foot abduction brace in order to avoid recurrences.

Non-compliance with periods of intolerance is very common for children during orthosis treatment. Parents' coping strategies are very important to avoid relapses. It is important to develop strategies to guide parents.

Background Treatment of hip instability in patients with lower lumbar level myelomeningocele is clinically challenging. Muscle transfer procedures, release of contractures, and intertrochanteric varus-rotation osteotomies have been described to restore weak or absent abductor strength as well as relocation of the hip. However, controlled trials evaluating hip instability in lower lumbar myelomeningocele are limited in the current literature. Questions/purposes The purposes of this study were to compare the (1) radiographic evidence for joint stability; (2) clinical outcomes (including abductor strength, ambulatory ability, and residual use of orthoses); and (3) complications between patients undergoing combined periarticular contracture releases and bony procedures with and without external oblique abdominal muscle transfers. Methods Between 2004 and 2013, 14 pediatric patients (16 hips) were treated for hip instability secondary to myelomeningocele using releases with or without muscle transfer. From those, 13 patients (15 hips) with a mean age of 6 years who had L3 to L5 level involvement were evaluated retrospectively. The patients were separated into two groups. Nine hips (in eight patients) were treated by performing a combination of external oblique abdominal muscle transfer to the greater trochanter, periarticular release of contractures, and bony procedures. These were compared with six hips (five patients) treated by performing a combination of periarticular release of contractures and bony procedures without external oblique abdominal muscle transfer. This study compared the results between two surgeons, one of whom always performed these muscle transfers in this setting and the other who never performed muscle transfer during the study period. The patients were clinically followed up at a mean of 41 months (range, 14-122 months); none of the patients was lost to followup. Radiographic evaluation criteria included Reimer's migration index, acetabular index, femoral neck-shaft angle, pelvic obliquity, and the presence of scoliosis. Clinical evaluation included muscle strength examination, periarticular contractures, necessity for using orthoses as walking aids, and Hoffer criteria of mobility. All complications were also noted from a chart review. Results There were no differences between the two groups regarding postoperative femoral head localization, reflecting the presence or absence of residual subluxation, according to Reimer's index (Reimer's index = 32%; range, 10%-40%, in the muscle transfer group compared Each author certifies that he or she, or a member of his or her immediate family, has no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research 1 editors and board members are on file with the publication and can be viewed on request. Each au...

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