3,031 results match your criteria Achondroplasia


The Functions and Effects of CUL3-E3 Ligases Mediated Non-degradative Ubiquitination.

Gene 2022 May 14:146562. Epub 2022 May 14.

The Affiliated Hospital of Medical School, Ningbo University, Ningbo 315020, China; Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathphysiology, Medical School of Ningbo University, Ningbo 315211, China. Electronic address:

Ubiquitination of substrates usually have two fates: one is degraded by 26S proteasome, and the other is non-degradative ubiquitination modification which is associated with cell cycle regulation, chromosome inactivation, protein transportation, tumorigenesis, achondroplasia, and neurological diseases. Cullin3 (CUL3), a scaffold protein, binding with the Bric-a-Brac-Tramtrack-Broad-complex (BTB) domain of substrates recognition adaptor and RING-finger protein 1 (RBX1) form ubiquitin ligases (E3). Based on the current researches, this review has summarized the functions and effects of CUL3-E3 ligases mediated non-degradative ubiquitination. Read More

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Achondroplasia and severe sensorineural hearing loss: The role of active bone conduction implants.

Cochlear Implants Int 2022 May 16:1-9. Epub 2022 May 16.

Department of Otolaryngology-Head and Neck Surgery, Schulich School of Medicine and Dentistry, Western University, London, Canada.

The BONEBRIDGE is a partially implantable, transcutaneous bone conduction device that can be used to treat conductive or mixed mild-to-moderate hearing loss in patients who do not attain sufficient improvement from conventional hearing aids. The following case report describes sequential bilateral BONEBRIDGE implantation in a 25-year-old patient with achondroplasia and bilateral mixed-hearing loss with a significant sensorineural component in the setting of chronic suppurative otitis media. Although the patient did not meet the approved BONEBRIDGE criteria, implantation was successful with improvements in audiological outcomes and self-reported quality of life. Read More

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Improved distribution of leg forces after fibular resection and synostosis.

J Exp Orthop 2022 May 16;9(1):43. Epub 2022 May 16.

Department of Orthopaedics, Nemours Children's Hospital Delaware, 1600 Rockland Road, Wilmington, DE, 19803, USA.

Purpose: Genu varum- a common symptom in achondroplasia- may lead to ankle valgus in children. Ankle valgus may be mitigated by tibiofibular synostosis, but this is not always the case. The mechanical environment around the growth plates plays an important role in ankle valgus. Read More

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Emerging drug targets for achondroplasia.

Authors:
Ravi Savarirayan

Expert Opin Ther Targets 2022 May 18:1-3. Epub 2022 May 18.

Murdoch Children's Research Institute, University of Melbourne, Parkville, Victoria, Australia.

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[Clinical features and mutations of children with achondroplasia].

Zhongguo Dang Dai Er Ke Za Zhi 2022 Apr;24(4):405-410

Department of Pediatrics, First Affiliated Hospital of Air Force Military Medical University, Xi'an 710032, China.

Objectives: To study the clinical features and fibroblast growth factor receptor 3 () gene mutations of children with achondroplasia (ACH) through an analysis of 17 cases.

Methods: A retrospective analysis was performed on the clinical data and gene detection results of 17 children with ACH who were diagnosed from January 2009 to October 2021.

Results: Of the 17 children with ACH, common clinical manifestations included disproportionate short stature (100%, 17/17), macrocephaly (100%, 17/17), trident hand (82%, 14/17), and genu varum (88%, 15/17). Read More

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Key measurement concepts and appropriate clinical outcome assessments in pediatric achondroplasia clinical trials.

Orphanet J Rare Dis 2022 05 7;17(1):182. Epub 2022 May 7.

Pfizer Inc, New York, USA.

Background: This study aimed to identify fit-for-purpose clinical outcome assessments (COAs) to evaluate physical function, as well as social and emotional well-being in clinical trials enrolling a pediatric population with achondroplasia. Qualitative interviews lasting up to 90 min were conducted in the US with children/adolescents with achondroplasia and/or their caregivers. Interviews utilized concept elicitation methodology to explore experiences and priorities for treatment outcomes. Read More

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Role of sperm DNA damage in creating de-novo mutations in human offspring: the 'post-meiotic oocyte collusion' hypothesis.

Reprod Biomed Online 2022 Mar 17. Epub 2022 Mar 17.

Priority Research Centre for Reproductive Science, College of Engineering, Science and Environment, The University of Newcastle, Callaghan New South Wales, Australia; Hunter Medical Research Institute, New Lambton Heights New South Wales, Australia. Electronic address:

Spermatogonial stem cells exhibit a low level of spontaneous mutation that is heavily impacted by paternal age via mechanisms that appear to involve the aberrant repair of DNA damage. This background de-novo mutation frequency can be increased 1000-fold by mutations affecting a key signal transduction pathway that confers upon its descendants a selective advantage, leading to clonal expansion and nests of mutant germ cells in the testes of ageing males. This 'selfish selection' model effectively explains the origin of several dominant developmental disorders, such as achondroplasia and Apert syndrome, but cannot be generalized to account for the majority of de-novo mutations where no selective advantage is apparent. Read More

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New insights in craniovertebral junction MR changes leading to stenosis in children with achondroplasia.

Childs Nerv Syst 2022 May 3. Epub 2022 May 3.

Claude Bernard Lyon 1 University, Lyon, France.

Purpose: To characterize natural history and early changes of craniovertebral junction stenosis in achondroplasia correlating with clinical and radiological outcome.

Methods: Retrospective measures on craniovertebral junction were performed blindly, on sagittal T2-weighted images, in 21 patients with achondroplasia referred from 2008 to 2020. Clinical and polysomnography data were retrospectively collected. Read More

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Gait in children with achondroplasia - a cross-sectional study on joint kinematics and kinetics.

BMC Musculoskelet Disord 2022 Apr 28;23(1):397. Epub 2022 Apr 28.

Department of Women's and Children's Health, Karolinska Institutet, Motoriklab, Q2:07, Karolinska University Hospital, 171 76, Stockholm, Sweden.

Background: Children with achondroplasia have extreme short stature due to short limbs, as well as several other clinical features that may affect their gait. The purpose of this cross-sectional study was to provide a detailed description of gait in children with achondroplasia compared to age-matched controls.

Methods: Between the years 2007 and 2010, 16 children with achondroplasia [mean age 9. Read More

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Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamics results of a long-acting C-type Natriuretic Peptide prodrug, TransCon CNP.

Br J Clin Pharmacol 2022 Apr 28. Epub 2022 Apr 28.

Ascendis Pharma A/S, Hellerup, Denmark.

Aim: TransCon CNP is a novel prodrug designed to provide sustained release of C-type natriuretic peptide (CNP) for once-weekly therapy, addressing the pathology leading to aberrant skeletal development in achondroplasia. This phase 1 trial was initiated to assess safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of TransCon CNP.

Methods: This randomized, placebo-controlled, single-ascending dose phase 1 trial was performed at 2 sites in Australia and enrolled 45 healthy adult males. Read More

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What Are the Risks and Functional Outcomes Associated With Bilateral Humeral Lengthening Using a Monolateral External Fixator in Patients With Achondroplasia?

Clin Orthop Relat Res 2022 Apr 25. Epub 2022 Apr 25.

Pediatric Orthopaedics, Deformity Reconstruction and Foot Surgery, University Hospital Muenster, Muenster, Germany.

Background: Many patients with achondroplasia experience functional impairments because of rhizomelic upper extremities (proximal limb shortening). Bilateral humeral lengthening may overcome these functional limitations, but it is associated with several risks, such as radial nerve palsy and insufficient bone regeneration. Only a few studies have reported on patient satisfaction and functional outcome after humeral lengthening in patients with achondroplasia. Read More

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Clinical and radiologic evaluation of a Turkish family with hypochondroplasia and a rare variant.

J Pediatr Endocrinol Metab 2022 Apr 20. Epub 2022 Apr 20.

Medical Genetics Department, Ankara University School of Medicine, Ankara, Turkey.

Objectives: Hypochondroplasia (HCH) is characterized by disproportionate short stature and regarded as a milder form of achondroplasia (ACH), which is another skeletal dysplasia, both caused by variants in fibroblast growth factor receptor 3 ( gene. HCH diagnosis is based on the clinical features and skeletal survey findings. The most common variant in HCH affects the codon 540, leading to substitution of asparagine with lysine in about 70% of patients. Read More

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The (extended) achondroplasia foramen magnum score has good observer reliability.

Pediatr Radiol 2022 Apr 9. Epub 2022 Apr 9.

Sheffield Children's Hospital NHS Foundation Trust, Sheffield, UK.

Background: Achondroplasia is the most common skeletal dysplasia. A significant complication is foramen magnum stenosis. When severe, compression of the spinal cord may result in sleep apnea, sudden respiratory arrest and death. Read More

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Cranial features of achondroplasia presenting with headaches.

Br J Hosp Med (Lond) 2022 03 31;83(3). Epub 2022 Mar 31.

Department of Medical Imaging, Mater Dei Hospital, Msida, Malta.

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Lower Back Pain Heralding Cauda Equina Syndrome in a Patient With Achondroplasia.

Cureus 2022 Feb 19;14(2):e22380. Epub 2022 Feb 19.

Physical Medicine and Rehabilitation, Hacettepe University Medical School, Ankara, TUR.

Achondroplasia is the most common cause of congenital dwarfism and is associated with multiple complications due to impaired skeletal development. Herein, we report a 21-year-old woman with achondroplasia experiencing lower back pain which progressed to lower limb weakness and urinary retention. Magnetic resonance imaging revealed decreased interpedicular distance and severe stenosis of the lumbosacral spinal canal. Read More

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February 2022

Infigratinib in children with achondroplasia: the PROPEL and PROPEL 2 studies.

Ther Adv Musculoskelet Dis 2022 21;14:1759720X221084848. Epub 2022 Mar 21.

Guy's and Saint Thomas' NHS Foundation Trust, London, UK.

Background: Achondroplasia is the most common short-limbed skeletal dysplasia resulting from gain-of-function pathogenic variants in fibroblast growth factor receptor 3 () gene, a negative regulator of endochondral bone formation. Most treatment options are symptomatic, targeting medical complications. Infigratinib is an orally bioavailable, FGFR1-3 selective tyrosine kinase inhibitor being investigated as a direct therapeutic strategy to counteract FGFR3 overactivity in achondroplasia. Read More

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Management of procidentia in an achondroplastic patient.

Int Urogynecol J 2022 Mar 21. Epub 2022 Mar 21.

Jamaica Hospital Medical Center, Queens, NY, 11418, USA.

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Airways and craniofacial assessment in children affected by achondroplasia with and without sleep-disordered breathing: quantitative magnetic resonance study.

Childs Nerv Syst 2022 Mar 12. Epub 2022 Mar 12.

Institute of Radiology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

Purpose: To identify MRI-based quantitative craniofacial variables linked to airways narrowing and obstructive sleep apnea (OSA) development in children with achondroplasia.

Methods: We evaluated skull base and midface MRI in two cohorts of children affected by achondroplasia, with (group 1) or without OSA (group 2). 3DFSPGR-T1weighted images were used to assess airways volume (nasopharynx, oropharynx, and laryngopharynx), jugular foramina (JF) and hypoglossal foramina (HF) areas, foramen magnum area, cervical cord area, and maxillary retrusion (SNA angle). Read More

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Collagen X Marker Levels are Decreased in Individuals with Achondroplasia.

Calcif Tissue Int 2022 Mar 11. Epub 2022 Mar 11.

Nemours Children's Hospital, Delaware, 1600 Rockland Road, Wilmington, DE, 19803, USA.

Collagen X marker (CXM) is a degradation fragment of collagen type X. It is a real-time biomarker of height velocity with established norms. Plasma C-type natriuretic peptide (CNP) and NTproCNP levels have also been found to correlate with growth velocity in the general population and are elevated in individuals with achondroplasia compared with age- and sex-matched controls. Read More

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Two-stage Bone Lengthening With Reuse of a Single Intramedullary Telescopic Nail in Patients With Achondroplasia.

J Pediatr Orthop 2022 Mar 7. Epub 2022 Mar 7.

Limb Lengthening and Reconstruction Unit, Orthopaedic Surgery and Traumatology Department Department of Orthopaedic Surgery and Traumatology Spinal Unit, Department of Orthopaedic Surgery and Traumatology Hip Unit, Department of Orthopaedic Surgery and Traumatology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.

Background: Patients with achondroplasia may benefit from limb-lengthening surgery with telescopic intramedullary nails (TIMNs). However, the 5-cm maximum length of the nails used in these patients in their original design may be insufficient. The aim of this research is to analyze the outcomes and complications after reusing the same TIMN for a second consecutive 5-cm lengthening in patients with achondroplasia. Read More

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Symptomatic thoracic ossified ligamentum flavum in achondroplasia: A case report and literature review.

Surg Neurol Int 2022 25;13:70. Epub 2022 Feb 25.

Pars Advanced and Minimally Invasive Medical Manners Research Center, Pars Hospital, Iran University of Medical Sciences, Tehran, Iran.

Background: In a patient with achondroplasia, it is rare to encounter thoracic cord compression due to both spinal stenosis and ossification of the yellow ligament (OYL).

Case Description: A 33-year-old achondroplastic female presented with a progressive spastic paraparesis attributed to thoracic stenosis combined with T10-T11 OYL. Following a laminectomy, the patient demonstrated a marked recovery of neurological function. Read More

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February 2022

Medical complications in children with achondroplasia.

Dev Med Child Neurol 2022 Mar 2. Epub 2022 Mar 2.

Department of Health Sciences, Macquarie University, Sydney, New South Wales, Australia.

Aim: To determine the rates of medical investigations, complications, interventions, and outcomes in children with achondroplasia.

Method: Children and adolescents with achondroplasia born between 2000 and 2019, aged between 0 and 18 years of age, and seen at The Children's Hospital at Westmead skeletal dysplasia clinic were included. Data were collected retrospectively from clinical records. Read More

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Longitudinal Imaging of the Skull Base Synchondroses Demonstrate Prevention of a Premature Ossification After Recifercept Treatment in Mouse Model of Achondroplasia.

JBMR Plus 2022 Feb 9;6(2):e10568. Epub 2021 Nov 9.

InnoSkel Biot France.

Achondroplasia is the most common form of short-limb dwarfism. In this disorder, endochondral ossification is impaired due to gain-of-function mutation in the Fibroblast Growth Factor Receptor 3 (FGFR3) gene. In addition to short limbs, cranial base bones are also affected leading to shortening of the skull base and to serious neurological complications associated with foramen magnum stenosis. Read More

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February 2022

New Drug Treats Pediatric Achondroplasia.

Am J Nurs 2022 03;122(3):18

Diane S. Aschenbrenner is a former member of the faculty at Notre Dame of Maryland University and the Johns Hopkins University School of Nursing. She coordinates Drug Watch:

The Food and Drug Administration has granted accelerated approval to vosoritide (Voxzogo) to treat children ages five years and older with achondroplasia who still have open epiphyses.Children prescribed vosoritide should have a meal and 240 to 300 mL of fluid in the hour prior to drug administration to prevent hypotensive episodes. Read More

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Mitral and tricuspid repair in an adult achondroplastic patient.

J Card Surg 2022 May 13;37(5):1425-1427. Epub 2022 Feb 13.

Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, New York, USA.

Achondroplasia is a rare genetic disorder with multiple anatomic abnormalities making surgery, and anesthesia more challenging. The reported cases of cardiac interventions in this population are few, and to the best of our knowledge, only 16 cases are documented. Herein, we represent the first case of mitral and tricuspid repair in one of these patients, which performed without the need for specific equipment with a smooth postoperative course. Read More

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Sagittal alignment at 3 years old determines future thoracolumbar kyphosis in achondroplasia: A prospective study with minimum 5-year follow-up from infancy.

N Am Spine Soc J 2021 Jun 13;6:100070. Epub 2021 May 13.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine 65, Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan.

Background: Little is known about the progression of Thoracolumbar kyphosis (TLK) in achondroplasia. The aim of the study was to evaluate natural progression of TLK and establish risk factors for progression.

Methods: We reviewed 21 patients (11 males, 10 females) diagnosed clinically and radiographically with achondroplasia as infants and followed for a minimum of 5 years from infancy, and analyzed to compare differences between data at 0, 1, 3, 5, 7-10, and 11-18 years old. Read More

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Experiences of children and adolescents living with achondroplasia and their caregivers.

Mol Genet Genomic Med 2022 04 9;10(4):e1891. Epub 2022 Feb 9.

BioMarin Pharmaceutical Inc., Novato, California, USA.

Background: Achondroplasia, caused by a pathogenic variant in the fibroblast growth factor receptor 3 gene (FGFR3), leads to significant multisystem complications across the lifespan that may affect the health-related quality of life (HRQoL) of individuals and families living with the condition.

Methods: The objective of this qualitative study was to describe the HRQoL of children and adolescents with achondroplasia and their caregivers. Thirty-four caregivers and 12 adolescents from the United States and Spain participated in one of eight focus groups or completed an individual interview, which was audio-recorded and transcribed. Read More

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[MATHEMATICAL MODELING OF OPTIONS FOR MOUNTING AN EXTERNAL FIXATION DEVICE ON THE TIBIA DURING ITS LENGTHENING].

Georgian Med News 2022 Jan(322):150-157

Sytenko Institute of Spine and Joints Pathology of the National Academy of Medical Sciences of Ukraine, Kharkov, Ukraine.

The main problem in the treatment of axial deformities and limb shortening in pediatric orthopedics is the presence of incomplete growth of the patient, which gives an unfavorable basis for the achieved correction. The most advanced technology for the treatment of deformities and limb shortening is the use of external fixation devices (AVF). Target. Read More

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January 2022

Meclozine Attenuates the MARK Pathway in Mammalian Chondrocytes and Ameliorates FGF2-Induced Bone Hyperossification in Larval Zebrafish.

Front Cell Dev Biol 2021 18;9:694018. Epub 2022 Jan 18.

Division of Molecular Therapeutics, Aichi Cancer Center Research Institute, Nagoya, Japan.

Meclozine has been developed as an inhibitor of fibroblast growth factor receptor 3 (FGFR3) to treat achondroplasia (ACH). Extracellular signal regulated kinase (ERK) phosphorylation was attenuated by meclozine in FGF2-treated chondrocyte cell line, but the site of its action has not been elucidated. Although orally administered meclozine promoted longitudinal bone growth in a mouse model of ACH, its effect on craniofacial bone development during the early stage remains unknown. Read More

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January 2022