Rare missense variants in are associated with severe adolescent idiopathic scoliosis.

Background: Scoliosis is the most common paediatric spinal deformity. More than 80% of scoliosis is idiopathic and appears during the adolescent growth spurt. Spinal fusion surgery is often required for patients with progressive adolescent idiopathic scoliosis (AIS), and the genetic risk factors for severe disease (defined here as curve >35 degrees) are largely unknown.

Tarsal coalition resection in children: Is it effective?

Tarsal coalitions in children are a group of disorders that typically present as a rigid flatfoot deformity. Operative treatment generally consists of resecting the coalition alone or resection plus flatfoot reconstructive procedures. The purpose of this study was to evaluate the rate and risk factors for complications, including infection, recurrence, and reoperation, following the surgical management of tarsal coalitions in children.

BrAIST-Calc: Prediction of Individualized Benefit From Bracing for Adolescent Idiopathic Scoliosis.

Study Design: Prospective multicenter study data were used for model derivation and externally validated using retrospective cohort data.

Objective: Derive and validate a prognostic model of benefit from bracing for adolescent idiopathic scoliosis (AIS).

Summary Of Background Data: The Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST) demonstrated the superiority of bracing over observation to prevent curve progression to the surgical threshold; 42% of untreated subjects had a good outcome, and 28% progressed to the surgical threshold despite bracing, likely due to poor adherence.

Clubfoot: Emphasis on the Complex and Atypical Subsets.

The Ponseti method has proven to be successful in the treatment of both isolated and non-isolated clubfoot. The method should be executed prior to any pediatric invasive procedures and likewise should be attempted with any pediatric recurrence. A thorough neurologic examination and attention to clinical signs will help distinguish the atypical clubfoot.

A pathogenic mechanism associated with myopathies and structural birth defects involves TPM2-directed myogenesis.

Nemaline myopathy (NM) is the most common congenital myopathy, characterized by extreme weakness of the respiratory, limb, and facial muscles. Pathogenic variants in Tropomyosin 2 (TPM2), which encodes a skeletal muscle-specific actin binding protein essential for sarcomere function, cause a spectrum of musculoskeletal disorders that include NM as well as cap myopathy, congenital fiber type disproportion, and distal arthrogryposis (DA). The in vivo pathomechanisms underlying TPM2-related disorders are unknown, so we expressed a series of dominant, pathogenic TPM2 variants in Drosophila embryos and found 4 variants significantly affected muscle development and muscle function.

Diagnostic yield of exome sequencing in congenital vertical talus.

Background: Congenital vertical talus (CVT), also known as "rocker-bottom foot", is a rare foot deformity associated with a dislocation of the talonavicular joint. Although genetic causes of CVT have been described in single isolated and syndromic families, whole-exome sequencing (WES) of large cohorts have not yet been reported.

Methods: In this study, 62 probands with CVT were evaluated for likely causative single nucleotide variants (SNVs) and copy number variants (CNVs) using WES.

Clubfoot.

Clubfoot or talipes equinovarus deformity is one of the most common anomalies affecting the lower extremities. This review provides an update on the outcomes of various treatment options used to correct clubfoot. The ultimate goal in the treatment of clubfoot is to obtain a fully functional and pain-free foot and maintain a long-term correction.

Whole Exome Sequencing in Individuals with Idiopathic Clubfoot Reveals a Recurrent Filamin B (FLNB) Deletion.

Background: Clubfoot, a congenital deformity that presents as a rigid, inward turning of the foot, affects approximately 1 in 1000 infants and occurs as an isolated birth defect in 80% of patients. Despite its high level of heritability, few causative genes have been identified, and mutations in known genes are only responsible for a small portion of clubfoot heritability.

Questions/purposes: (1) Are any rare gene variants enriched (that is, shared) in unrelated patients with isolated clubfoot? (2) Are there other rare variants in the identified gene (Filamin B) in these patients with clubfoot?

Methods: Whole-exome sequence data were generated from a discovery cohort of 183 unrelated probands with clubfoot and 2492 controls.

A Decade in Review after Idiopathic Scoliosis Was First Called a Complex Trait-A Tribute to the Late Dr. Yves Cotrel for His Support in Studies of Etiology of Scoliosis.

Adolescent Idiopathic Scoliosis (AIS) is a prevalent and important spine disorder in the pediatric age group. An increased family tendency was observed for a long time, but the underlying genetic mechanism was uncertain. In 1999, Dr.

Late Effects of Clubfoot Deformity in Adolescent and Young Adult Patients Whose Initial Treatment Was an Extensive Soft-tissue Release: Topic Review and Clinical Case Series.

Children with congenital clubfoot often have residual deformity, pain, and limited function in adolescence and young adulthood. These patients represent a heterogeneous group that often requires an individualized management strategy. This article reviews the available literature on this topic while proposing a descriptive classification system based on a review of patients at our institution who underwent surgery for problems related to previous clubfoot deformity during the period between January 1999 and January 2012.

Rare and de novo coding variants in chromodomain genes in Chiari I malformation.

Chiari I malformation (CM1), the displacement of the cerebellum through the foramen magnum into the spinal canal, is one of the most common pediatric neurological conditions. Individuals with CM1 can present with neurological symptoms, including severe headaches and sensory or motor deficits, often as a consequence of brainstem compression or syringomyelia (SM). We conducted whole-exome sequencing (WES) on 668 CM1 probands and 232 family members and performed gene-burden and de novo enrichment analyses.

Genetic association and characterization of FSTL5 in isolated clubfoot.

Talipes equinovarus (clubfoot, TEV) is a congenital rotational foot deformity occurring in 1 per 1000 births with increased prevalence in males compared with females. The genetic etiology of isolated clubfoot (iTEV) remains unclear. Using a genome-wide association study, we identified a locus within FSTL5, encoding follistatin-like 5, significantly associated with iTEV.

MYH3-associated distal arthrogryposis zebrafish model is normalized with para-aminoblebbistatin.

Distal arthrogryposis (DA) is group of syndromes characterized by congenital joint contractures. Treatment development is hindered by the lack of vertebrate models. Here, we describe a zebrafish model in which a common MYH3 missense mutation (R672H) was introduced into the orthologous zebrafish gene smyhc1 (slow myosin heavy chain 1) (R673H).

Selective Dorsal Rhizotomy for the Treatment of Spastic Hemiplegic Cerebral Palsy.

Background Selective dorsal rhizotomy (SDR) can remove spasticity in cerebral palsy (CP). Spastic hemiplegia is associated with spasticity in the upper and lower limbs on one side. Only a single report described the outcome of SDR specifically in patients with spastic hemiplegic CP.

Selective Dorsal Rhizotomy for the Treatment of Spastic Triplegic Cerebral Palsy.

Background Spastic triplegia is a recognized subtype of cerebral palsy (CP). In the course of treating spastic triplegic children with selective dorsal rhizotomy (SDR), we found that some children who had "minimal or mild involvement" in the stronger arm improved strikingly after undergoing SDR. Some of them became independent ambulators, which was an outcome that is not usually achieved in spastic quadriplegic children.

Treatment of femoral fractures in children aged two to six.

Aims: Current American Academy of Orthopaedic Surgeons (AAOS) guidelines for treating femoral fractures in children aged two to six years recommend early spica casting although some individuals have recommended intramedullary stabilization in this age group. The purpose of this study was to compare the treatment and family burden of care of spica casting and flexible intramedullary nailing in this age group.

Methods: Patients aged two to six years old with acute, non-pathological femur fractures were prospectively enrolled at one of three tertiary children's hospitals.

Improving musculoskeletal health for children and young people - A 'call to action'.

This chapter describes the musculoskeletal (MSK) context in children and young people as an important contributor to the global non-communicable disease burden. Through selected MSK conditions, we describe the impact on patients, families and communities and highlight the challenges that need to be addressed. We focus on opportunities for better working together and describe exemplar initiatives to raise awareness, workforce capacity building, models of care and research agendas to have a greater global context.

The paediatric global musculoskeletal task force - 'towards better MSK health for all'.

There is increasing concern about the emerging global non-communicable diseases (NCDs) burden. The focus has mainly been on NCDs in adults but it is important that MSK morbidity in both children and adults is included in strategic planning. There have been considerable advances in the understanding and treatment options for children and young people (CYP) and clinical outcomes are improving for those who can access such high quality care.