Exome sequencing (ES) and gene panels can be considered for fetal anomalies. Whether ES offers substantial benefit over targeted panels is not clear. Secondary analysis of a prospective cohort study of pregnancies with fetal anomalies undergoing ES. We included cases with isolated or multisystem skeletal dysplasias, CNS anomalies, and/or cardiac anomalies. Participants underwent ES, and pathogenic (P) and likely pathogenic (LP) variants were reported. The primary outcome was the percentage of P/LP variants found on ES that would have been identified on panels available prenatally in the United States. 109 cases with relevant anomalies were included in the primary analysis. Of these, 20 (18%) had P/LP variant(s) identified on ES-4 multisystem, 4 isolated CNS, 6 isolated cardiac, and 6 isolated skeletal dysplasia. Gene panels would have detected 50 (88%) of the variants identified by ES. Yield was highest for isolated skeletal anomalies (100%) compared to CNS and cardiac malformations (75% and 67%, p=0.02). Yield was higher for isolated anomalies than multisystem anomalies (median 91.5% vs. 50%, p<0.01). In cases of fetal anomalies with genetic etiologies identified on ES, commercial gene panels had variable diagnostic yields. Panels performed worst for multisystem anomalies.

Lower extremity Ilizarov surgery, a common procedure for correcting bone deformities, is often associated with reduced physical activity (PA) and functional decline. The home-based PA intelligent programme (HB-PAIP) has shown promise in improving postoperative outcomes. However, standardised, intelligent programmes specifically designed for patients undergoing lower extremity Ilizarov surgery are lacking. This study aims to evaluate the effects of a 6-month home-based intelligent interaction programme on PA levels and to assess its impact on mental health, self-efficacy and quality of life among patients with lower extremity Ilizarov. A total of 166 participants aged ≥18 years who have undergone lower extremity Ilizarov surgery will be randomly allocated to either the HB-PAIP group or control group (CG) at a 1:1 ratio. The HB-PAIP group will receive a 6-month, structured and algorithm-guided home rehabilitation programme via an intelligent motion rehabilitation management system, whereas CG will receive traditional care. The assessments will be conducted at baseline, 3 months (mid-intervention) and 6 months (post-intervention). The primary outcome is functional mobility assessed by the Timed Up-and-Go test. Secondary outcomes include the 10-metre walking test, the passive ankle range of motion, the Activity of Daily Living score, the Visual Analogue Scale score, the mental status measured using the Hamilton Anxiety and Hamilton Depression Scales and serum levels of haemoglobin and albumin. This study was initially approved by the Human Ethics Review Board of the Second Affiliated Hospital of Zhejiang University School of Medicine on 26 January 2024 (approval number: 20240139). The protocol amendment was approved on 28 January 2026 (approval number: 20260134). Results will be disseminated through peer-reviewed publications and presentations at relevant scientific conferences. ChiCTR2400093880.

Total Knee Arthroplasty in Post-Polio Residual Paralysis: A Systematic Review and Pooled Analysis of Its Outcomes and Complications.

Mutations in the Rab33b protein that lead to the skeletal disease Smith-McCort dysplasia result in unstable proteins and altered autophagy function.

Real-world outcomes of vosoritide in achondroplasia: A systematic review and meta-analysis of multinational clinical evidence.

Achondroplasia is a skeletal dysplasia associated with multisystem complications including genu varum, which causes pain and limits mobility. Vosoritide, a targeted treatment for achondroplasia, improves growth in children and has an established safety profile, but its effect on genu varum is unclear. Data were collected from 183 participants from randomized, double-blind, placebo-controlled phase 2 (CANOPY ACH-2I [111-206; NCT03583697]) and phase 3 (CANOPY ACH-3 [111-301; NCT03197766]) studies evaluating vosoritide (weight-based dose of 15 or 30 µg/kg/day) in children aged 0-5 and >5 years, respectively. Anterior/posterior lower limb radiographs were taken at baseline and 1 year to measure parameters associated with genu varum. Differences in least-squares mean (LSM) change from baseline were calculated for vosoritide vs placebo using an analysis of covariance model. In both studies, age at treatment initiation and sex distribution were generally balanced between vosoritide and placebo (except 58% males received vosoritide in CANOPY ACH-2I). After 1 year of vosoritide treatment vs placebo, tibial bowing decreased in children who initiated treatment aged <5 years (n = 40) and remained stable in those ≥5 years (n = 57). Vosoritide-treated participants with evidence of abnormal fibular growth at baseline had reduced overall and distal fibular overgrowth vs placebo. Children aged ≥5 years improved in ankle joint to distal fibula physis distance (difference in LSM change from baseline, -0.07, P = .010) and fibula/tibia ratio (-0.025, P < .0001), and children aged 2-5 years had improved fibula/tibia ratio (-0.033, P = .0032). Preliminary results suggest vosoritide may improve or limit genu varum in children with achondroplasia.

The growth plate: Zonal architecture, plasticity, and endocrine control of linear growth.

Mucopolysaccharidosis IVA (MPS IVA) is caused by the accumulation of undegraded glycosaminoglycans due to the deficiency of the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) enzyme. MPS IVA manifests as progressive systemic skeletal dysplasia. Gene therapy (GT) is potentially a one-time treatment in which the enzyme is continuously produced, circulated, and delivered to target tissues. However, immune responses to gene products can diminish therapeutic efficacy. We hypothesized that oral delivery of tolerogenic peptides induces immune tolerance to human GALNS (hGALNS) in MPS IVA mice, enhancing therapeutic efficacy. Neonatal mice deficient in mouse GALNS (mGALNS) were treated orally with three T-cell/B-cell epitope peptides or hGALNS protein on alternate days from day 3 after birth to day 20 before intravenous injection with AAV9 vectors encoding human GALNS on day 30. The results are encouraging, with anti-hGALNS antibodies undetectable in the plasma of orally administered peptide groups. hGALNS enzyme activities in plasma and tissues were higher in the orally treated groups than in the non-tolerized control group. Keratan sulfate levels in plasma, liver, and bone were normalized. Complete correction for heart vacuolization was achieved in peptide-treated groups, and partial correction for bone pathology was observed in all GT-treated groups. Overall, oral tolerance induction using immunodominant peptides promises to significantly enhance the efficacy of AAV-GT for MPS IVA.

Primary osteoporosis can be caused by pathogenic variants in multiple genes. Recently, rare heterozygous variants in SGMS2, encoding SGMS2, have been identified to cause early-onset osteoporosis or more severe skeletal dysplasia. The incidence of pathogenic SGMS2 variants and their consequent clinical features, however, remain limited. This study aimed to identify the prevalence and nature of SGMS2 variants in Finnish patients with genetically undiagnosed idiopathic early-onset osteoporosis. All eleven exons and exon-intron boundaries of SGMS2 were sequenced. In a cohort of 44 patients (42 females and two males, median age at the time of recruitment 60 years, range 25-76 years), we identified one rare heterozygous missense variant (c.715T>C, p.Phe239Leu) and three intronic variants with unknown functional consequences; no pathogenic or likely pathogenic variants were found. Our results suggest that pathogenic variants in SGMS2 are not a common cause of early-onset idiopathic osteoporosis in Finnish patients. Further studies in larger cohorts and variable skeletal phenotypes are needed to increase our understanding of the role of SGMS2 in skeletal fragility.

Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive skeletal dysplasia. It is often associated with short stature, metaphyseal abnormalities, hair hypoplasia and immune dysfunction. This case describes a pregnant woman in her mid-30s with two previous children diagnosed with CHH with molecular confirmation of two pathogenic variants of the ribonuclease mitochondrial RNA processing gene. The couple is healthy and non-consanguineous. Routine ultrasound examination of the current pregnancy suggested this fetus was also likely to be affected. The couple opted not to perform invasive prenatal diagnosis. Umbilical cord blood was collected at birth for genetic testing, confirming the diagnosis. CHH has a significant impact on the quality of life of those affected. Genetic counselling may help parents understand the disease and its prognosis. Obstetric ultrasound plays an important role in the diagnosis by allowing early detection of suspected cases as well as assessing fetal growth.

ABSTRACT This study examines a case of skeletal dysplasia in an adult male (B290) from the Bronze Age at the site of Ban Non Wat, Northeast Thailand. Skeletal dysplasia, a group of genetic disorders affecting bone and cartilage growth, presents diagnostic challenges due to overlapping clinical features. B290 exhibited rhizomelia, humeral varus deformity, coxa vara, and block thoracic vertebra. A thorough differential diagnosis comparing 56 skeletal dysplasias identified that B290's skeletal pathology was consistent with conditions including hypochondroplasia or pseudoachondroplasia. The case contributes to a growing body of literature identifying extreme short stature and/or skeletal dysplasia in adults from the prehistory of Mainland Southeast Asia, indicating inclusion of differently abled individuals in society was not rare in this region, potentially highlighting a shared understanding of human value.

Telescoping intramedullary rods have transformed the management of long bone deformity and fragility fractures in children, yet complications and revision surgery remain common. This systematic review synthesizes outcomes across telescoping systems to evaluate complication and revision rates, telescoping success, and design evolution to guide implant selection and surgical decision-making in pediatric orthopedics. A search was conducted through July 2025 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies reporting outcomes of telescoping rods in pediatric patients were included. Due to heterogeneity, results were synthesized descriptively and presented as weighted means per operated bone. Thirty-three studies (861 patients; 2054 rods) were included. Weighted mean complication and revision rates were 49.6% and 25.7% for Bailey-Dubow rods, 61.1% and 24.5% for Sheffield rods, 37.1% and 30.5% for Fassier-Duval rods, 14.9% and 9.0% for corkscrew-locking rods, and 46.7% and 6.7% for distal-female rods. Telescoping success was 48% for Bailey-Dubow, 74% for Fassier-Duval, 94% for corkscrew, and 100% for distal-female designs. Variation in follow-up duration and definitions of complications contributed to differences in reported rates. Modern telescoping rods have reduced migration and mechanical failure compared with earlier designs, yet complication and revision rates remain substantial. Newer systems show encouraging early results but require longer follow-up for validation. Differences in bone anatomy and biomechanics strongly influence implant performance, underscoring the need to tailor rod selection to individual bones. This review consolidates published complication and revision rates across telescoping rod designs, establishing a foundation for comparison as newer implants are introduced and long-term outcome data become available. III.

Smith-McCort dysplasia (SMC) is a rare autosomal recessive disease characterised by short-trunk dwarfism, skeletal dysplasia, and platyspondyly. It is closely related to Dyggve–Melchior–Clausen syndrome, but patients with SMC have normal mental functions. Both disorders are caused by mutations in the Dymeclin gene (DYM). We report the case of an 8-year-old girl presenting with disproportionate short stature, rhizomelic limb shortening, pectus carinatum, Harrison sulcus, and metaphyseal dysplastic changes in the knee, hip and shoulder joints. Genetic analysis identified a mutation in the DYM gene: Homozygous splice site variant (c.1126-2A&gt;G). Notably, echocardiography revealed a small secundum atrial septal defect, a finding rarely associated with SMC.

Ilizarov correction of extreme anterior tibial bowing (≈100°) secondary to fibrous dysplasia: a case report from Afghanistan

Short stature is the most common reason for referral to pediatric endocrinology. Diagnosis primarily relies on history, physical exam and auxological assessment. Although growth hormone (GH) stimulation tests (GHST) are controversial, they remain relevant for determining eligibility for GH therapy. Individuals with idiopathic short stature (ISS) exhibit normal GHST results and lack features of skeletal dysplasia or syndromic conditions. Despite the strong genetic contribution to adult height (70%-90%), genetic testing is not included in routinely evaluation of children with short stature. To assess the added diagnostic value of exome sequencing (ES) in children with short stature evaluated by GHST with variable outcomes. Sixty children with short stature were evaluated by ES and stratified into three groups based on GHST peak concentrations: group a, ≤7 ng/mL; group b, 7-10 ng/mL, and group c, ≥10 ng/mL (n = 20 per group). Identified variants were analyzed and genotype-phenotype associations explored. Disease-causing variants were identified in 8/60 children (13.3%), most commonly in the GH peak 7-10 ng/mL group (n = 4), followed by ≥10 ng/mL (n = 3) and ≤7 ng/mL (n = 1) groups. Most pathogenic variants were in genes related to growth plate development; a subset was associated with syndromic conditions. Fourteen candidate variants of uncertain significance potentially linked to short stature were detected in 13 children (21.6%). The limited correlation between GHST results and genetic findings highlights the diagnostic value of ES. Integrating genetic testing into the evaluation of short stature can enhance etiological understanding and support personalized management, particularly in ISS cases and decisions regarding GH therapy.

Pathologies of the cervical spine in skeletal syndromes and dysplasias.

UFMylation: biology mechanisms, functions, and clinical implications.

ABSTRACTObjectiveTo characterize the metacarpophalangeal pattern profile (MCPP) of healthy children and adolescents from São Paulo, Brazil, and to establish percentile curves by chronological age (CA), bone age (BA), and sex using the LMS method. Additionally, to compare these findings with previous population‐based data and to apply the derived standards to patients with skeletal dysplasias.MethodsLeft hand and wrist radiographs were obtained from healthy individuals and age‐matched patients with confirmed skeletal dysplasias. Tubular bone lengths were compared across CA and BA, against prior normative studies, and with dysplastic cohorts using Student's t‐test. Patient Z‐scores were calculated from LMS parameters generated from the healthy population.ResultsWe analyzed 974 radiographs from healthy subjects and 83 from patients (18 hypochondroplasia, 27 achondroplasia, 14 osteogenesis imperfecta, 24 Turner syndrome). In healthy participants, hand bone lengths correlated significantly with CA and BA. Compared with international reference data, differences in mean metacarpal and phalangeal lengths were noted. Patients with achondroplasia and hypochondroplasia exhibited markedly reduced Z‐scores relative to controls, whereas those with Turner syndrome showed reductions of up to 1.8 SD in the fourth metacarpal. Patients with osteogenesis imperfecta demonstrated no significant deviations.ConclusionThis study established MCPP reference percentiles for Brazilian children and adolescents using the LMS method. Bone measurements showed consistent associations with CA and BA. Although differences were observed relative to international cohorts, the generated standards effectively discriminated dysplastic phenotypes, particularly achondroplasia and hypochondroplasia, supporting the use of MCPP analysis as an adjunct tool for evaluating short stature and suspected skeletal dysplasias.

Radiographs of the head and spine are now obtained less frequently, and their clinical significance has become limited. Nevertheless, they remains useful for the overall assessment of the cranial and spinal structures. In particular, X-rays still provide high diagnostic value in hematologic disorders, drug-induced conditions, metabolic bone diseases, skeletal dysplasia, congenital anomalies, and bone tumors. This article reviews representative diseases in which a radiography can serve as the initial clue for diagnosis, including conditions discovered incidentally.

Real-world safety and age-dependent effectiveness of vosoritide in achondroplasia: A single-center retrospective analysis of transition from growth hormone to vosoritide.