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JCI Insight 2021 May 10;6(9). Epub 2021 May 10.

Université de Paris, Imagine Institute, Laboratory of Molecular and Physiopathological Bases of Osteochondrodysplasia, INSERM UMR 1163, F‑75015, Paris, France.

Activating mutations in fibroblast growth factor receptor 3 (FGFR3) and inactivating mutations in the natriuretic peptide receptor 2 (NPR2) guanylyl cyclase both result in decreased production of cyclic GMP in chondrocytes and severe short stature, causing achondroplasia (ACH) and acromesomelic dysplasia, type Maroteaux, respectively. Previously, we showed that an NPR2 agonist BMN-111 (vosoritide) increases bone growth in mice mimicking ACH (Fgfr3Y367C/+). Here, because FGFR3 signaling decreases NPR2 activity by dephosphorylating the NPR2 protein, we tested whether a phosphatase inhibitor (LB-100) could enhance BMN-111-stimulated bone growth in ACH. Read More

Int J Paleopathol 2021 May 10;33:196-208. Epub 2021 May 10.

School of Human Evolution and Social Change, Arizona State University, PO Box 872402, Tempe, AZ, 85287-2402, USA. Electronic address:

Objective: The article reviews the study of rare diseases and their nomenclature, emerging government policies and initiatives, and the concerns voiced by the modern rare disease communities. An interpretive model is then presented for the bioarchaeological interpretations of individuals with paleopathological evidence of rare diseases.

Materials: In demonstration of the application of the proposed framework, we evaluate the skeletal remains of an adult female (EZ 3-7-1) excavated in the 1980s from the Middle Woodland (50BCE-CE400) context of the Elizabeth site (11PK512) in the lower Illinois Valley, USA. Read More

Am J Med Genet C Semin Med Genet 2021 May 13. Epub 2021 May 13.

School of Obstetrics and Gynecology, Women's Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou, People's Republic of China.

Dwarfism has been depicted in various Chinese art forms including literature, sculpture, and painting. This article examines several representative Chinese works of art from different ages of Chinese history, in order to glimpse the living situations of people with dwarfism, their professions and social status, as well as the social attitude toward them in China. We highlight " (Shan Hai Jing, translated as the Classic of Mountains and Seas), a remarkable collection of myths and illustrations which documented the existence of dwarf communities where the residents were capable of producing high-quality grains. Read More

Growth Horm IGF Res 2021 Apr 30;57-58:101392. Epub 2021 Apr 30.

UCL Great Ormond Street Institute of Child Health, London, UK.

Objective: We sought to obtain a better understanding of the burden of short stature using a systematic literature review.

Methods: Studies of the burden of short stature, of any cause in adults and children, were searched using Embase, MEDLINE and Cochrane databases in April 2020, capturing publications from 2008 onwards. Case series and populations with adult-onset growth hormone deficiency (GHD) were excluded. Read More

Case Rep Endocrinol 2021 15;2021:9944552. Epub 2021 Apr 15.

Complicated Metabolic Bone Disorders Clinic, Osteoporosis and Bone Metabolism Unit, Department of Endocrinology, Singapore General Hospital, Singapore.

X-linked hypophosphatemia (XLH) is the most prevalent form of hereditary hypophosphatemic rickets associated with phosphate wasting. However, its diagnosis is often missed, resulting in patients presenting late in the course of the disease when complications such as tertiary hyperparathyroidism and renal failure have already set in. Phosphate and calcitriol replacement, both of which have undesirable consequences of their own, have historically been the main stay of therapy. Read More

Proc (Bayl Univ Med Cent) 2021 Jan 28;34(3):419-421. Epub 2021 Jan 28.

Department of Radiology, Yale New Haven Health Bridgeport Hospital, Bridgeport, Connecticut.

Achondroplasia is a genetic condition caused by disordered endochondral ossification, which leads to rhizomelic dwarfism and midfacial hypoplasia. Additionally, several morphologic changes in the temporal bone are thought to at least partially contribute to hearing loss in these patients. We present a patient with achondroplasia who presented with hearing loss and was referred to radiology for temporal bone imaging. Read More

Sci Transl Med 2021 May;13(592)

Department of Biology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic.

Achondroplasia is the most prevalent genetic form of dwarfism in humans and is caused by activating mutations in FGFR3 tyrosine kinase. The clinical need for a safe and effective inhibitor of FGFR3 is unmet, leaving achondroplasia currently incurable. Here, we evaluated RBM-007, an RNA aptamer previously developed to neutralize the FGFR3 ligand FGF2, for its activity against FGFR3. Read More

Br J Radiol 2021 Apr 29:20210223. Epub 2021 Apr 29.

Royal National Orthopaedic Hospital NHS Trust, London, UK.

Achondroplasia is the commonest hereditary skeletal dysplasia exhibiting dwarfism with characteristic rhizomelic (proximal) shortening of the limbs. It is predominantly linked with an autosomal dominant inheritance, but sporadic mutations can occur which are associated with advanced maternal age. Approximately 1 in every 25 000-30 000 live births are affected, and the overall life expectancy is marginally reduced by ~10 years. Read More

Stem Cell Res 2021 Apr 5;53:102322. Epub 2021 Apr 5.

Department of Obstetrics and Gynecology, Department of Fetal Medicine and Prenatal Diagnosis, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. Electronic address:

Achondroplasia (ACH; MIM #100800) is an autosomal dominant genetic disease caused by gain-of-function mutations in FGFR3 gene and results in short-limb dwarfism. Here, we generated an induced pluripotent stem cell line GZHMCi004-A derived from umbilical cord blood mononuclear cells (UCBMCs) of a fetus with heterozygous G380R mutation in FGFR3 gene. This iPSC line is a valuable in vitro model to study the pathological mechanism and the treatment of ACH. Read More

Orv Hetil 2021 04 10;162(17):683-688. Epub 2021 Apr 10.

3 Heim Pál Országos Gyermekgyógyászati Intézet, Alvásdiagnosztikai és Terápiás Labor, Budapest.

Összefoglaló. Az achondroplasia kialakulásáért az FGFR3-gén mutációja tehető felelőssé, mely a porc növekedési lemezében található chondrocyták érésében okoz zavart. Az esetbemutatásban szereplő lánygyermeknél a születést követő első hónapban a klinikai, laboratóriumi és röntgenvizsgálatok alapján achondroplasia igazolódott. Read More

Orphanet J Rare Dis 2021 Apr 7;16(1):156. Epub 2021 Apr 7.

Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Background: Previous studies have found a high prevalence of obstructive sleep apnea (OSA) in children with achondroplasia, but clinical studies on this complication in adults with achondroplasia are lacking.

Objectives: This population-based, cross-sectional study investigated the prevalence, severity, and predictive factors of OSA in Norwegian adults with achondroplasia.

Methods: We collected clinical data on 49 participants. Read More

Int J Paleopathol 2021 Apr 1;33:94-102. Epub 2021 Apr 1.

German Archaeological Institute, Department of Natural Sciences, Berlin, Germany.

Objective: This paper aims to provide a quantitative estimation of the representation of diseases defined as rare today in the bioarchaeological literature and to outline the reasons for this.

Materials: A 45-year bibliometric study of publications in seven bioarchaeological journals, along with two journals and editorial groups of broader scientific focus.

Methods: Analyses of distribution patterns of the search hits and diachronic trends for achondroplasia, autosomal-dominant osteopetrosis, osteogenesis imperfecta, and osteopoikilosis, compared to those for tuberculosis as control measure of coverage. Read More

JCI Insight 2021 May 10;6(9). Epub 2021 May 10.

Departments of Integrative Biology and Physiology and.

Activating mutations in the fibroblast growth factor receptor 3 (FGFR3) or inactivating mutations in guanylyl cyclase-B (GC-B), also known as NPR-B or Npr2, cause short-limbed dwarfism. FGFR3 activation causes dephosphorylation and inactivation of GC-B, but the contribution of GC-B dephosphorylation to achondroplasia (ACH) is unknown. GC-B7E/7E mice that express a glutamate-substituted version of GC-B that cannot be inactivated by dephosphorylation were bred with mice expressing FGFR3-G380R, the most common human ACH mutation, to determine if GC-B dephosphorylation is required for ACH. Read More

Childs Nerv Syst 2021 Mar 29. Epub 2021 Mar 29.

Shriners Hospitals for Children-Philadelphia, 3551 N Broad St, Philadelphia, PA, 19140, USA.

Bimodal intraoperative neuromonitoring (IONM), combining transcranial motor-evoked potentials (tcMEP) and somatosensory-evoked potentials (SSEP), enables real-time detection and prevention of spinal cord injury during pediatric spinal deformity correction. Although rare, false-positive and false-negative signal alerts have been reported. However, no previously published accounts have described the use of postoperative neurophysiological testing to both identify new-onset neurological injury and guide reintervention. Read More

Childs Nerv Syst 2021 Mar 29. Epub 2021 Mar 29.

Department of Neurosurgery, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, Gifu, 501-1194, Japan.

Hydrocephalus, a complication of achondroplasia, requires treatment when it is symptomatic. Hydrocephalus associated with achondroplasia is often treated with ventriculoperitoneal shunting, and endoscopic third ventriculostomy (ETV) is rarely performed in these patients. Here, we report the case of an 18-month-old boy with achondroplasia and progressive hydrocephalus who underwent ETV. Read More

Internist (Berl) 2021 May 29;62(5):486-495. Epub 2021 Mar 29.

Orthopädisches Zentrum für Muskuloskeletale Forschung, Universität Würzburg, Brettreichstr. 11, 97074, Würzburg, Deutschland.

Delineating the genetic background and the underlying pathophysiology of rare skeletal dysplasias enables a broader understanding of these disorders as well as novel perspectives regarding differential diagnosis and targeted development of therapeutic approaches. Hypophosphatasia (HPP) due to genetically determined Alkaline Phosphatase deficiency exemplifies this development. While an enzyme replacement therapy could be established for severe HPP with the prevailing bone manifestation, the clinical impact of not immediately bone-related manifestations just being successively understood. Read More

Sci Prog 2021 Jan-Mar;104(1):368504211003782

BioMarin (U.K.) Limited, London, UK.

Achondroplasia causes narrowing of the foramen magnum and the spinal canal leading to increased mortality due to cervicomedullary compression in infants and significant morbidity due to spinal stenosis later in adulthood. Vosoritide is a C-natriuretic peptide analogue that has been shown to improve endochondral ossification in children with achondroplasia. The objective of this trial is to evaluate the safety of vosoritide and whether vosoritide can improve the growth of the foramen magnum and spinal canal in children that may require decompression surgery. Read More

Indian J Radiol Imaging 2020 Oct-Dec;30(4):436-447. Epub 2021 Jan 13.

Department of Radiodiagnosis, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.

Spine radiograph is an essential component of a skeletal survey. It provides important diagnostic clues to various types of skeletal dysplasia. In some conditions, a spine radiograph alone may be diagnostic and characteristic; but mostly, it yields more value as a part of the complete skeletal survey. Read More

Dis Model Mech 2021 Apr 23;14(4). Epub 2021 Apr 23.

Laboratory of Molecular and Physiopathological Bases of Osteochondrodysplasia, INSERM UMR 1163, Imagine Institute, Paris 75015, France.

Achondroplasia (ACH), the most common form of dwarfism, is caused by a missense mutation in the gene coding for fibroblast growth factor receptor 3 (FGFR3). The resulting increase in FGFR3 signaling perturbs the proliferation and differentiation of chondrocytes (CCs), alters the process of endochondral ossification and thus reduces bone elongation. Increased FGFR3 signaling in osteoblasts (OBs) might also contribute to bone anomalies in ACH. Read More

Arthroplast Today 2021 Apr 24;8:24-28. Epub 2021 Feb 24.

Department of Orthopaedic Surgery, University of California, Los Angeles, Los Angeles, CA, USA.

Genu varum in patients with achondroplasia is common and is often exacerbated by the associated generalized ligamentous laxity. Despite this, development of knee osteoarthritis is rare. There are only a few previously published case reports of total knee arthroplasty in this population. Read More

Lakartidningen 2021 02 26;118. Epub 2021 Feb 26.

professor, överläkare, barnkliniken, Universitetssjukhuset Örebro; Örebro universitet; Skelettdysplasiteamet och barnendokrinologiska mottagningen, Astrid Lindgrens barnsjukhus, Karolinska universitetssjukhuset, Stockholm.

Achondroplasia is the most common form of monogenic skeletal dysplasia and is caused by activating mutations in fibroblast growth factor receptor 3 (FGFR3) resulting in exaggerated MAPK signaling in the growth cartilage chondrocytes and thus reduced growth. C-type natriuretic peptide (CNP) stimulates growth by inhibiting MAPK signaling in growth plate cartilage. Several new treatments that target these pathways are currently in clinical trials for the treatment of achondroplasia. Read More

Am J Med Genet A 2021 05 27;185(5):1481-1485. Epub 2021 Feb 27.

Department of Health Professions, Macquarie University, New South Wales, Australia.

The aim of this study was to estimate the childhood prevalence of achondroplasia, trends over time in birth prevalence, and age at diagnosis in Australia. Children born between 1990 and 2019 with a clinical and radiological and/or molecular diagnosis of achondroplasia were identified from a tertiary hospital servicing New South Wales (NSW) and the Australian Capital Territory (ACT) and compared with population data from the Australian Bureau of Statistics. Childhood prevalence of achondroplasia, based on children ≤19 years of age and resident in NSW/ACT on June 30, 2019 (n = 109), was 5. Read More

J Biomech 2021 Apr 12;119:110313. Epub 2021 Feb 12.

Movement Analysis Laboratory, Central Remedial Clinic, Clontarf, Dublin 3, Ireland. Electronic address:

Achondroplasia is an autosomal dominant disorder that has been reported to be the most common condition associated with severe disproportionate short stature. A limited number of studies exist in the literature reporting kinematic abnormalities in children with Achondroplasia. Reported deviations include increased pelvic tilt, flexed knees during stance and excessive hip abduction. Read More

Global Spine J 2021 Feb 22:2192568221989291. Epub 2021 Feb 22.

Department of Orthopaedic Surgery, 34732Peking Union Medical College Hospital (PUMCH), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Study Design: Retrospective cohort study.

Objective: We aimed to evaluate the safety and validity of posterior vertebral column resection (pVCR) for severe thoracolumbar kyphosis (TLK) in the achondroplasia (ACH) patients.

Methods: Seven ACH patients (male: female = 6:1) who underwent pVCR procedures due to severe TLK from December 2008 to December 2017 in the authors' hospital were included in this retrospective study. Read More

Global Spine J 2021 Feb 18:2192568221994786. Epub 2021 Feb 18.

Hospital for Special Surgery, New York, NY, USA.

Study Design: Retrospective case series.

Objective: To report contemporary rates of complications and subsequent surgery after spinal surgery in patients with skeletal dysplasia.

Methods: A case series of 25 consecutive patients who underwent spinal surgery between 2007 and 2017 were identified from a single institution's skeletal dysplasia registry. Read More

Neurosci Biobehav Rev 2021 May 10;124:267-290. Epub 2021 Feb 10.

Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA, 02478, USA. Electronic address:

For patients diagnosed with a rare musculoskeletal or neuromuscular disease, pain may transition from acute to chronic; the latter yielding additional challenges for both patients and care providers. We assessed the present understanding of pain across a set of ten rare, noninfectious, noncancerous disorders; Osteogenesis Imperfecta, Ehlers-Danlos Syndrome, Achondroplasia, Fibrodysplasia Ossificans Progressiva, Fibrous Dysplasia/McCune-Albright Syndrome, Complex Regional Pain Syndrome, Duchenne Muscular Dystrophy, Infantile- and Late-Onset Pompe disease, Charcot-Marie-Tooth Disease, and Amyotrophic Lateral Sclerosis. Through the integration of natural history, cross-sectional, retrospective, clinical trials, & case studies we described pathologic and genetic factors, pain sources, phenotypes, and lastly, existing therapeutic approaches. Read More

Orphanet J Rare Dis 2021 02 12;16(1):81. Epub 2021 Feb 12.

Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, 03080, Seoul, Republic of Korea.

Background: Cervical myelopathy and hydrocephalus occasionally occur in young children with achondroplasia. However, these conditions are not evaluated in a timely manner in many cases. The current study presents significant predictors for cervical myelopathy and hydrocephalus in young children with achondroplasia. Read More

Neuropediatrics 2021 Feb 12. Epub 2021 Feb 12.

Department of Pediatrics, Section of Pediatric Neurology and Developmental Neuroscience, Baylor College of Medicine, Houston, Texas, United States.

Wien Med Wochenschr 2021 Apr 11;171(5-6):102-110. Epub 2021 Feb 11.

Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria.

Children and adolescents with bone and growth disorders require interdisciplinary care from various specialists including pediatric radiologists with a focus on musculoskeletal disorders. This article covers routine topics, differential diagnoses, and selected research imaging in children with osteogenesis imperfecta (OI), X‑linked hypophosphatemic rickets (XLH), achondroplasia, and other bone and growth disorders from the standpoint of a tertiary referral center. Read More

J Pediatr Orthop 2021 Apr;41(4):e328-e336

Department of Bone Reconstruction Surgery, San Juan de Dios Hospital, Pamplona, Navarra, Spain.

Purpose: The purpose of this study was to analyze the long-term results of humeral lengthening in achondroplastic patients and make suggestions on the most appropriate surgical technique to improve patient outcomes.

Methods: Fifty-four humeral lengthening procedures performed in 27 achondroplastic patients were reviewed. Elongations were performed by means of callotasis with unilateral external fixation. Read More