Vosoritide treatment for children with hypochondroplasia: a phase 2 trial. Hypochondroplasia is a rare autosomal dominant skeletal dysplasia due to activating variants in . It presents with disproportionate short stature with a wide range of clinical severity. There are currently no approved medications to treat short stature in children with hypochondroplasia. Vosoritide is a C-type natriuretic peptide analog that was recently approved for improving growth in children with achondroplasia. We aimed to evaluate the safety and efficacy of vosoritide in children with hypochondroplasia. We conducted a single-arm, phase 2, open-label trial at a single centre in the USA and enrolled 26 children with hypochondroplasia. The trial consists of a 6-month observation period to establish a baseline
Failure to diagnose hypochondroplasia by prenatal diagnosis: a case report. Hypochondroplasia (HCH) is a common nonlethal skeletal dysplasia caused by pathogenic variations in the fibroblast growth factor receptor 3 (FGFR3) gene, and HCH has similar clinical manifestations with achondroplasia (ACH), which can be screened during the fetal period by prenatal ultrasound testing and diagnosed
Hypochondroplasia gain-of-function mutation in FGFR3 causes defective bone mineralization in mice. Hypochondroplasia (HCH) is a mild dwarfism caused by missense mutations in fibroblast growth factor receptor 3 (FGFR3), with the majority of cases resulting from a heterozygous p.Asn540Lys gain-of-function mutation. Here, we report the generation and characterization of the first mouse model and aging processes, with potential implications for the management of elderly patients with hypochondroplasia and osteoporosis.
Identification of a novel mutation of FGFR3 gene in a large Chinese pedigree with hypochondroplasia by next-generation sequencing: A case report and brief literature review. Hypochondroplasia (HCH) is the mildest form of chondrodysplasia characterized by disproportionate short stature, short extremities, and variable lumbar lordosis. It is caused by mutations in fibroblast growth factor receptor
A novel S269C mutation in fibroblast growth factor receptor 3 in a Japanese child with hypochondroplasia Functionally activating mutations in fibroblast growth factor receptor 3 (FGFR3) can cause four types of autosomal dominant skeletal dysplasia with short-limbed dwarfism that include the mildest phenotype, hypochondroplasia (HCH). A novel mutation (c.805A>T, p.S269C) was identified
An International Study of Infigratinib in Children with Hypochondroplasia (HCH) ACCEL2/3 is a Phase 2/3 study. The purpose of the Phase 2 portion of the study (ACCEL2/3) is to evaluate the efficacy and safety, of infigratinib in children with hypochondroplasia (HCH) receiving infigratinib, at one of two doses, of who have completed at least 26 weeks of participation in QED-sponsored ACCEL
Dentoalveolar Abscesses Not Associated with Caries or Trauma: A Diagnostic Hallmark of Hypophosphatemic Rickets Initially Misdiagnosed as Hypochondroplasia Hypophosphatemic rickets is a rare genetic disorder involving the regulation of fibroblast growth factor 23 (FGF23), a phosphaturic agent, clinically showing bowing of the legs, short stature and dentoalveolar abscesses. A 7-year-old boy , with previous hypochondroplasia diagnosis, was referred to our pediatric dentistry clinic presenting short stature, bone deformities and sinus tracts at deciduous teeth apex levels not related with trauma, restorations or dental caries. After deciduous teeth extraction, due to root resorption and mobility, light microscopy exhibited typical hypophosphatemic dentin, and micro-computed tomography revealed
Acanthosis nigricans in a Japanese boy with hypochondroplasia due to a K650T mutation in FGFR3 Acanthosis nigricans (AN) is observed in some cases of skeletal dysplasia. However, AN has occasionally been reported in patients with hypochondroplasia (HCH), and a clinical diagnosis is sometimes difficult when its physical and radiological features are mild. Mutations in the gene encoding
Prospective Clinical Assessment Study in Children With Hypochondroplasia This is a long-term, multicenter, non-interventional study of children ages 2.5 to \<17 years with hypochondroplasia (HCH). The objective is to evaluate growth, HCH-related medical complications, health-related quality of life, functional abilities and cognitive functions of study participants. Data collected will contribute
Interventional Study of Vosoritide for the Treatment of Children With Hypochondroplasia The intent and design of this Phase 3 study is to assess vosoritide as a therapeutic option for the treatment of children with hypochondroplasia (HCH). This is a Phase 3 randomized, stratified, placebo-controlled, double-blind multicenter study to evaluate the effect of 52 weeks of daily vosoritide
A Multicenter Multinational Observational Study of Children With Hypochondroplasia This study will assess growth over time and the clinical course of HCH in children by collecting growth measurements and other variables of interest. undefined
C-type natriuretic peptide (CNP) plasma levels are elevated in subjects with achondroplasia, hypochondroplasia, and thanatophoric dysplasia. C-type natriuretic peptide (CNP) is a crucial regulator of endochondral bone growth. In a previous report of a child with acromesomelic dysplasia, Maroteaux type (AMDM), caused by loss-of-function of the CNP receptor (natriuretic peptide receptor-B [NPR-B ]), plasma levels of CNP were elevated. In vitro studies have shown that activation of the MAPK kinase (MEK)/ERK MAPK pathway causes functional inhibition of NPR-B. Achondroplasia, hypochondroplasia, and thanatophoric dysplasia are syndromes of short-limbed dwarfism caused by activating mutations of fibroblast growth factor receptor-3, which result in overactivation of the MEK/ERK MAPK pathway. The purpose
Prenatal magnetic resonance imaging detection of temporal lobes and hippocampal anomalies in hypochondroplasia. Hypochondroplasia (HCH) is a genetic skeletal dysplasia, inherited in an autosomal dominant fashion. About 50-70% of HCH patients have a mutation in FGFR3 gene and in the majority of cases it is a de novo mutation. Recent magnetic resonance imaging studies on relative large cohorts
Early and late fracture following extensive limb lengthening in patients with achondroplasia and hypochondroplasia. Two types of fracture, early and late, have been reported following limb lengthening in patients with achondroplasia (ACH) and hypochondroplasia (HCH). We reviewed 25 patients with these conditions who underwent 72 segmental limb lengthening procedures involving the femur
Registry for Patients With Achondroplasia / Hypochondroplasia (OMPR-Ach/Hy) This registry is a observational, single-center study designed to collect clinical data on patients with achondroplasia and hypochondroplasia. undefined
Treatment of Varus Deformities of the Lower Limbs in Patients with Achondroplasia and Hypochondroplasia Angular deformities of the lower limbs are a common clinical problem encountered in pediatric orthopaedic practices particularly in patients with osteochondrodysplasias. The varus deformity is more common than the valgus deformity in achondroplasia and hypochondroplasia patients because
this treatment approach. Positive outcomes of vosoritide in achondroplasia have inspired trials of vosoritide in other genetic diseases causing short stature related to the CNP/NPR2 pathway (24). An Italian registry study of individuals with achondroplasia or hypochondroplasia (NCT05328050) and an investigator-initiated, open-label, single-arm study (NCT04219007) of the effects of vosoritide in patients with various skeletal dysplasias, including hypochondroplasia, ACAN variants, SHOX gene defects, Noonan syndrome, and neurofibromatosis type 1, are expected to provide preliminary information about the effectiveness of vosoritide for treatment of these other skeletal disorders.There are other treatments in clinical development that target the FGFR3/CNP pathway for treatment of achondroplasia, including
intracellular signals through the STAT and MAPK pathways5 (Fig. 1).Although achondroplasia can be diagnosed on a clinical basis without molecular tests, genetic testing can lead to rapid confirmation when limited clinical signs are present (for example, prenatally). Thus, genetic testing can help distinguish achondroplasia from hypochondroplasia or other skeletal dysplasias and can enable increased precision