Search Our Scientific Publications & Authors

J Neurosurg Pediatr 2018 Dec 14:1-7. Epub 2018 Dec 14.

OBJECTIVEThe goal of this study was to determine the rates of screening and surgery for foramen magnum stenosis in children with achondroplasia in a large, privately insured healthcare network.METHODSRates of screening and surgery for foramen magnum stenosis in children with achondroplasia were determined using de-identified insurance claims data from a large, privately insured healthcare network of over 58 million beneficiaries across the United States between 2001 and 2014. Cases of achondroplasia and screening and surgery claims were identified using a combination of International Classification of Diseases diagnosis codes and Current Procedural Terminology codes. Read More

Biochem Soc Trans 2018 Dec 13;46(6):1753-1770. Epub 2018 Dec 13.

Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.

The receptor tyrosine kinase family of fibroblast growth factor receptors (FGFRs) play crucial roles in embryonic development, metabolism, tissue homeostasis and wound repair via stimulation of intracellular signalling cascades. As a consequence of FGFRs' influence on cell growth, proliferation and differentiation, FGFR signalling is frequently dysregulated in a host of human cancers, variously by means of overexpression, somatic point mutations and gene fusion events. Dysregulation of FGFRs is also the underlying cause of many developmental dysplasias such as hypochondroplasia and achondroplasia. Read More

Musculoskelet Surg 2018 Dec 10. Epub 2018 Dec 10.

ICATME, Hospital Universitari Quiron-Dexeus, Carrer Sabino de Arana, 5-19, 08028, Barcelona, Spain.

Background: Elongation in patients with achondroplasia provides better overall skeletal proportionality and significantly improves such individuals' access to their perineal region to self-manage personal hygiene. This paper describes our surgical technique and outcomes for bilateral humeral lengthening in achondroplasia patients over 26 years.

Methods: Ours was a retrospective study of 55 patients with achondroplasia-related short stature, in whom bilateral humeral lengthening was performed from 1990 to 2016. Read More

Medicine (Baltimore) 2018 Nov;97(48):e13269

Neonatal Service, Metabolic Unit, Department of Pediatrics, Santiago de Compostela University Hospital, IDIS (Health Research Institute of Santiago de Compostela), Ciberer, Spain.

Rationale: Hypophosphatasia (HPP) is a very rare metabolic bone disease caused by loss-of-function mutations in the ALPL gene encoding the tissue nonspecific alkaline phosphatase. The severe neonatal form is considered lethal but insights into manifestations of the disease can help to increase our knowledge of the natural history for an early initiation of treatment and improvement of survival.

Patient Concerns: We report the case of a newborn in which his fetal imaging showed findings of skeletal dysplasia disorder, considering initially achondroplasia as a potential diagnosis. Read More

BMC Musculoskelet Disord 2018 Nov 29;19(1):417. Epub 2018 Nov 29.

Department of Orthopaedic Surgery and Institute for Rare Diseases, Korea University Medical Center, Guro Hospital, 148 Gurodong-ro, Guro-gu, Seoul, 152-703, Republic of Korea.

Background: Hip flexion contracture often occurs after femoral lengthening in patients with achondroplasia, but few studies have investigated its development in these patients. The purpose of this study was to analyze sustained hip flexion contracture in achondroplasia patients who underwent femoral lengthening and to identify contributing factors.

Methods: This study included 34 patients with achondroplasia who underwent femoral lengthening (mean age at operation, 11. Read More

J Biol Chem 2018 Nov 28. Epub 2018 Nov 28.

University of Macau, Macao.

CRISPR/Cas9 is a powerful technology widely used for genome editing, with the potential to be used for correcting a wide variety of deleterious disease-causing mutations. However, the technique tends to generate more indels (insertions and deletions) than precise modifications at the target sites, which might not resolve the mutation and could instead exacerbate the initial genetic disruption. We sought to develop an improved protocol for CRISPR/Cas9 that would correct mutations without unintended consequences. Read More

Gait Posture 2018 Nov 16;68:150-154. Epub 2018 Nov 16.

Health, Exercise and Active Living Research, Manchester Metropolitan University, United Kingdom.

Background: Achondroplasia is characterised by a shorter appendicular limb-to-torso ratio, compared to age matched individuals of average stature (controls). Previous work shows gait kinematics of individuals with Achondroplasia differing to controls, but no global quantification of gait has been made in adults with Achondroplasia.

Aim: The aim of this study was to quantify gait differences between a group of adult males with Achondroplasia and controls during self-selected walking (SSW) using the Gait Profile Score (GPS). Read More

J Pediatr Orthop B 2018 Nov 15. Epub 2018 Nov 15.

IV Division of Orthopaedics and Traumatology, 'Gaetano Pini' Orthopaedic Institute.

Staged leg lengthening allows achondroplastic dwarfs to reach nearly normal height, but it takes long periods of external fixation and it can be burdened by delayed unions. Between 2009 and 2013, eight achondroplastic dwarfs showed delayed unions in the callus formation during femoral lengthening stages in our institute. We performed in-situ injections of bone marrow-derived stem cell concentrates. Read More

JNMA J Nepal Med Assoc 2018 Mar-Apr;56(211):683-686

Institute of Medicine, Maharajgunj Medicine Campus, Tribhuvan University, Maharajgunj, Kathmandu, Nepal.

Introduction: Achondroplasia is the most common form of skeletal dysplasia of genetic origin in humans which is characterized by disproportionate rhizomelic dwarfism. Heterozygous mutation in the transmembrane domain of the FGFR3 gene (4p16.3) occurs as a de novo mutation in most of the cases. Read More

Am J Med Genet A 2018 Oct 31:e40506. Epub 2018 Oct 31.

Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.

Acanthosis nigricans (AN) in those with achondroplasia has been reported occasionally in the literature previously. Other disorders arising from constitutive activation of FGFR3 also manifest AN at various frequencies. We assessed the prevalence of AN in a sequential series of 477 individuals with achondroplasia. Read More

Pediatr Endocrinol Rev 2018 Sep;16(Suppl 1):123-128

Division of Pediatric Endocrinology and Metabolism, Children's Medical Center, Osaka City General Hospital, Miyakojima, Osaka, Japan.

Achondroplasia (ACH) is the most common form of skeletal dysplasia causing rhizomelic, short-limb short stature. Short- and long-term clinical trials have been conducted with rhGH, with similar results across these studies. At supraphysiological dose of GH, height gain of 1-1. Read More

Genome Res 2018 12 24;28(12):1779-1790. Epub 2018 Oct 24.

Clinical Genetics Group, MRC-Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom.

Mosaic mutations present in the germline have important implications for reproductive risk and disease transmission. We previously demonstrated a phenomenon occurring in the male germline, whereby specific mutations arising spontaneously in stem cells (spermatogonia) lead to clonal expansion, resulting in elevated mutation levels in sperm over time. This process, termed "selfish spermatogonial selection," explains the high spontaneous birth prevalence and strong paternal age-effect of disorders such as achondroplasia and Apert, Noonan and Costello syndromes, with direct experimental evidence currently available for specific positions of six genes (, , , , , and ). Read More

Ann Transl Med 2018 Sep;6(17):343

Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy.

Childhood obstructive sleep apnea syndrome (OSAS) is characterized by anatomical and functional upper airway abnormalities as pathophysiological determinants, and clinical symptoms are frequently clear. OSAS is widely described in rare genetic disorders, such as achondroplasia, Down syndrome, Prader-Willi syndrome, Pierre Robin sequence, and mucopolysaccharidosis. Craniofacial and upper airway involvement is frequently morbid conditions. Read More

J Craniofac Surg 2018 Nov;29(8):2186-2191

Department of Oral and Maxillofacial Surgery, University of Lille, CHU Lille.

In this study, the authors aimed to describe orocraniofacial features and to suggest orthodontic-surgical managements in achondroplasia, based on a literature review. The authors focused on skeletal and dentoalveolar malocclusion in order to highlight the place of orthognathic surgery, based on our experience of 3 patients. Maxillary hypoplasia in achondroplasia typically results in an Angle class III malocclusion with an anterior open bite. Read More

Am J Med Genet A 2018 Nov 1;176(11):2359-2364. Epub 2018 Oct 1.

Department of Pediatrics, McGovern Medical School at UTHealth, Houston, Texas.

Sudden death and higher mortality are recognized in achondroplasia, with acute brainstem compression, a common cause of mortality in children <4 years and cardiovascular deaths being more prevalent in adults. Although, changes in clinical management have improved survival, mortality is still higher than in the general population. The aim of this multicenter clinic-based study was to assess the rate and causes of mortality in patients seen in clinic since 1986. Read More

Sleep Breath 2018 Sep 5. Epub 2018 Sep 5.

Pediatric noninvasive ventilation and sleep unit, AP-HP, Hôpital Necker Enfants-Malades, Paris, France.

Purpose: Co-sleeping is common in children with co-morbid conditions. The aim of the study was to analyze the prevalence and determinants of parent-child co-sleeping in children with co-morbid conditions and sleep-disordered breathing and the impact on parental sleep.

Methods: Parents of consecutive children undergoing a sleep study filled in a questionnaire on co-sleeping. Read More

Ann Med Surg (Lond) 2018 Oct 27;34:17-22. Epub 2018 Aug 27.

Department of Orthopedic Surgery, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Introduction: The most cases of excessive femoral anteversion may be asymptomatic, because the he hip joint is a ball joint. However, when the hip, knee, or ankle joint is in a pathological state, excessive femoral anteversion may not be compensated for and induce symptoms.

Case Report: A 16-year-old female with achondroplasia. Read More

Am J Med Genet A 2018 Jul;176(7):1675-1679

Department of Medical Genetics, University of Washington Medical Center, Seattle, Washington.

Pathogenic variants in the fibroblast growth factor receptor 3 (FGFR3) gene are responsible for a broad spectrum of skeletal dysplasias, including achondroplasia (ACH). The classic phenotype of ACH is caused by two highly prevalent mutations, c.1138G > A and c. Read More

Am J Med Genet A 2018 Sep 27;176(9):1819-1829. Epub 2018 Aug 27.

Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.

The aims of this study was to construct references for sitting height, leg length, arm span, relative sitting height (sitting height/height), and foot length and to discuss the development for these anthropometric variables in achondroplasia. Sex-specific references covering ±2 SD are presented for ages 2-20 years. Legs and arms in achondroplasia are already at 2 years of age considerably shorter than in the general population and this deviation increases with age. Read More

J Glaucoma 2018 Oct;27(10):e165-e167

Department of Ophthalmology, University of Florida, Gainesville, FL.

We report the first case to our knowledge of a 1-week-old female infant with familial inherited achondroplasia associated with bilateral congenital onset glaucoma, posterior embryotoxon and iris hypoplasia suggestive of ocular Axenfeld-Rieger anomaly. Read More

Endocrinol Diabetes Metab Case Rep 2018 26;2018. Epub 2018 Jul 26.

Department of Diabetes and Endocrinology, Flinders Medical Centre, Bedford Park, South Australia, Australia.

A 40-year-old man with achondroplasia presented with symptoms of hypogonadism, low libido and gynaecomastia. He was found to have hypergonadotropic hypogonadism, and karyotype and fluorescent hybridisation analysis showed -positive 46, XX disorder of sex development (DSD). He was tested to have the common activating mutation of the gene implicated in achondroplasia, indicating that he had the two rare conditions independently, with an extremely low incidence of 1 in 400 million. Read More

Front Physiol 2018 20;9:867. Epub 2018 Jul 20.

Health, Exercise and Active Living Research, Manchester Metropolitan University, Manchester, United Kingdom.

Achondroplasia is a genetic mutation of fibroblast growth factor receptor resulting in impaired growth plate development in long bones due to lower collagen turnover. Despite the characteristic shorter stature and lower strength in Achondroplasic groups, little is known of the tendon mechanical properties under loading. The aim of this study was therefore to conduct a between measure design of patella tendon (PT) mechanical properties (stress, strain, stiffness and Young's Modulus) in 10 men with Achondroplasia (22 ± 3 years) and 17 male controls (22 ± 2 years). Read More

Am J Med Genet A 2018 Aug 2;176(8):1723-1734. Epub 2018 Aug 2.

Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.

As growth references for achondroplasia are limited to reports from United States, Japan, Argentina, and Australia, the aim of this study was to construct growth references for height, weight, head circumference, and body mass index (BMI) from a European cohort of children with achondroplasia and to discuss the development of these anthropometric variables. A mix of cross-sectional and longitudinal, retrospective, and prospective data from 466 children with achondroplasia and 4,375 measuring occasions were modeled with generalized additive model for location, scale and shape (GAMLSS) to sex-specific references for ages 0 to 20 years. Loss in height position, that is, reduction in height standard deviation scores, occurred mainly during first 2 years of life while pubertal growth seemed normal if related to adult height. Read More

Pediatr Pulmonol 2018 Oct 1;53(10):1422-1428. Epub 2018 Aug 1.

Pediatric Noninvasive Ventilation and Sleep Unit, AP-HP, Hôpital Necker-Enfants Malades, Paris, France.

Introduction: Current guidelines recommend initiating continuous positive airway pressure (CPAP) in children during an overnight in-hospital titration study. Due to a shortage of hospital beds and economic constraints, we started a program for outpatient initiation of CPAP in selected children with obstructive sleep apnea (OSA).

Methods: Objective CPAP compliance and efficacy were evaluated in consecutive children enrolled in an outpatient CPAP program when they fulfilled the following criteria: persistent OSA, age >6 months, stable condition, family living in the Parisian area and agreeing with a regular follow-up. Read More

Prenat Diagn 2018 Oct 19;38(11):821-828. Epub 2018 Aug 19.

Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing, China.

Objective: To explore the feasibility and accuracy of a noninvasive prenatal test for fibroblast growth factor receptor 3 (FGFR3)-related skeletal dysplasia based on next-generation sequencing (NGS) of plasma cell-free DNA.

Method: Fragmented genome DNA (gDNA) of fetuses with achondroplasia (ACH) and thanatophoric dysplasia type I (TD I) was mixed with postdelivery maternal plasma cell-free DNA to generate spiked samples of different modeled fetal fractions. Multiplex polymerase chain reaction was used to amplify the 19 FGFR3 loci, and the amplification products were then sequenced by NGS to detect the fetal mutant alleles. Read More

J Maxillofac Oral Surg 2018 Sep 28;17(3):296-300. Epub 2017 Nov 28.

1Maxillo-Facial Surgery Department, E.O. Ospedali Galliera, Via Mura delle Cappuccine 14, 16128 Genoa, Italy.

Patients with hypoplasia of the midface normally present a flattening of their facial profile due to insufficient development of the nose and maxilla. Treatment aimed to restore function and an aesthetic appearance calls for a Le Fort III osteotomy and the advancement of the midfacial segment either through distraction or interposition of autogenous bone blocks. However, drawbacks in using autogenous bone suggest that use of alternative graft material may be advisable. Read More

Clinics (Sao Paulo) 2018 07 2;73:e324. Epub 2018 Jul 2.

Unidade de Genetica, Instituto da Crianca (ICR), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR.

Objectives: To characterize the natural history of 39 achondroplastic patients diagnosed by clinical, radiological and molecular assessments.

Methods: Observational and retrospective study of 39 patients who were attended at a public tertiary level hospital between 1995 and 2016.

Results: Diagnosis was made prenatally in 11 patients, at birth in 9 patients and within the first year of life in 13 patients. Read More

Pediatr Rev 2018 Jul;39(7):359-362

Department of Medical Genetics and Genomic Medicine, Saint Peter's University Hospital, New Brunswick, NJ.

Childs Nerv Syst 2018 Nov 29;34(11):2275-2281. Epub 2018 Jun 29.

Department of Neurosurgery, Brain Research Institute, University of Niigata, 1-757, Asahimachi-dori, Chuo-ku,, Niigata City, Niigata, 951-8585, Japan.

Objective: Management of cervicomedullary compression due to foramen magnum stenosis in achondroplasia remains controversial, especially for patients with no symptoms or mild symptoms. We examined the effectiveness of polysomnography (PSG) as an indicator for cervicomedullary decompression treatment.

Methods: We retrospectively reviewed nine achondroplasia cases (mean age 1 year and 9 months) treated from 2008 to 2015. Read More

Med Princ Pract 2018 21;27(5):451-458. Epub 2018 Jun 21.

Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy.

Objective: Craniofacial disharmony in skeletal diseases is strongly associated with sleep-disordered breathing. This study was aimed at studying the sleep respiratory patterns in young children with rare skeletal disorders.

Design: This retrospective study included children with achondroplasia (ACH), osteogenesis imperfecta (OI) and Ellis van Creveld Syndrome. Read More

J Fr Ophtalmol 2018 Jun 13;41(6):e287-e289. Epub 2018 Jun 13.

Centre hospitalier Hrazem, CHU Hassan II-Fès, Atlas, avenue Hassan-II, BP1835 Fès, Morocco.

Otol Neurotol 2018 Jul;39(6):732-738

Centre of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem.

Objectives: The purpose of this study is to report the results of a comprehensive etiological work-up for congenitally deaf children including targeted next generation sequencing.

Study Design: Retrospective case review.

Setting: Tertiary referral center. Read More

Surg Case Rep 2018 Jun 8;4(1):53. Epub 2018 Jun 8.

Department of Cardiovascular Surgery, Kumamoto Rosai Hospital, 1670 Takehara, Yatsushiro, Kumamoto, 866-8533, Japan.

Background: Achondroplasia is an inherited disorder and the most common type of short-limbed dwarfism in human beings, affecting more than 250,000 individuals worldwide. To the best of our knowledge, no study has reported a correlation between achondroplasia and aortic dissection. Here, we report a rare case of acute type A aortic dissection repair in a patient with achondroplasia. Read More

World Neurosurg 2018 Aug 5;116:e1188-e1193. Epub 2018 Jun 5.

Division of Pediatric Neurosurgery, Department of Neurosurgery, Primary Children's Medical Center, University of Utah, Salt Lake City, Utah, USA.

Objective: The need for neurosurgical supervision as well as the general safety and utility of dynamic magnetic resonance imaging (MRI) of the cervical spine in children remains controversial. We present the largest descriptive cohort study of cervical flexion-extension MRI scans in pediatric patients to help elucidate the safety and utility of this technique.

Methods: We retrospectively reviewed all cervical spine MRI scans performed at Lucile Packard Children's Hospital at Stanford from 2009 to 2015. Read More

J Pediatr Orthop B 2018 Nov;27(6):535-540

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Increase in the magnitude of lengthening during the limb lengthening procedure involves a high risk of decreased range of motion (ROM) in adjacent joints. Even though patients with achondroplasia can tolerate a relatively larger amount of lengthening owing to its inherent soft-tissue laxity, they often exhibit significant joint contractures during extensive lengthening. In the present study, we evaluated temporal changes in the ROM of the hip, knee, and ankle joints throughout the treatment period in 12 limbs of six patients with achondroplasia who had undergone extensive tibial lengthening. Read More

Genet Med 2018 Jun 5. Epub 2018 Jun 5.

Division of Genetics, Birth Defects and Metabolism, Ann & Robert H. Lurie Children's Hospital of Chicago, Professor of Pediatrics, Feinberg School of Medicine, Northwestern University, Evanston, Illinois, USA.

Purpose: To examine results of magnetic resonance imaging (MRI), polysomnograms (PSG), and patient outcomes in patients with achondroplasia in light of recent screening recommendations for infants with achondroplasia.

Methods: We reviewed medical records of 49 patients with achondroplasia followed at our institution between September 1997 and January 2017, including physical exams, MRIs, PSGs (when available), and surgical histories. Appropriate PSG data were available for 39 of these patients. Read More

Eur J Orthop Surg Traumatol 2018 Dec 24;28(8):1569-1572. Epub 2018 May 24.

Biomedical Research Foundation of the Academy of Athens, Athens, Greece.

Pycnodysostosis or Maroteaux-Lamy syndrome is a genotypic bone disorder, with autosomal recessive inheritance, individualized by Lamy and Maroteaux in 1962. It is characterized by diffuse condensation of the skeleton with thickening of the cortex and narrowing of the medullary cavity. This condensation is reminiscent of the one observed in Albers-Schönberg disease, which differs essentially in dysmorphism of the skull (no closure of fontanelles, gaping sutures, hypoplasia of the lower jaw with open mandibular angle) and extremities (hypoplasia or osteolysis of the phalanges). Read More

Curr Neurol Neurosci Rep 2018 May 23;18(7):38. Epub 2018 May 23.

Department of Pediatrics, Children's Mercy Hospital, 2401 Gillham Road, Kansas City, MO, USA.

Purpose Of Review: Congenital malformations of the central nervous system may be seen in isolation or in association with syndromes that have multiorgan involvement. Among the potential health challenges these children may face, sleep concerns are frequent and may include chronic insomnia, sleep-related breathing disorders, and circadian rhythm disorders.

Recent Findings: In this review, we describe recent research into sleep disorders affecting children with congenital malformations of the CNS including visual impairment, septo-optic dysplasia, agenesis of the corpus callosum, Aicardi syndrome, Chiari malformation, spina bifida, achondroplasia, Joubert syndrome, fetal alcohol spectrum disorders, and congenital Zika syndrome. Read More

Front Physiol 2018 18;9:410. Epub 2018 Apr 18.

Health, Exercise and Active Living Research Centre, Department of Exercise and Sport Science, Manchester Metropolitan University, Manchester, United Kingdom.

The disproportionate body mass and leg length of Achondroplasic individuals may affect their net oxygen consumption ([Formula: see text]O) and metabolic cost (C) when walking at running compared to those of average stature (controls). The aim of this study was to measure submaximal [Formula: see text]O and C during a range of set walking speeds (SWS; 0.56 - 1. Read More

Cir Cir 2018 ;86(1):89-98

Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social. Guadalajara, Jal. México.

Background: Achondrogenesis is a skeletal dysplasia characterized primarily by short stature, severe micromelia, short and narrow chest, prematurity, polyhydramnios, fetal hydrops, and in utero or neonatal death. Based on the radiological and histopathological findings, there are three types of achondrogenesis: type 1A (Houston-Harris), type 1B (Fraccaro) and type 2 (Langer-Saldino).

Clinical Case: A premature female product was studied whose clinical, radiological and histopathological characteristics were compatible with achondrogenesis Type 1A. Read More

Am J Med Genet A 2018 May;176(5):1225-1231

Médico Residente de Genética Médica, Departamento de Genética Humana, Instituto Nacional de Pediatría, Ciudad de México, México.

Achondroplasia-hypochondroplasia (ACH-HCH) complex is caused by the presence of two different pathogenic variants in each allele of FGFR3 gene. Only four patients with confirmed molecular diagnoses have been reported to date, and the phenotype has not been fully defined. Here, we describe a Mexican patient with a confirmed molecular diagnosis of ACH-HCH complex. Read More

PLoS One 2018 13;13(4):e0195876. Epub 2018 Apr 13.

Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France.

Background: Achondroplasia is a rare genetic disease is characterized by abnormal bone development and early obesity. While the bone aspect of the disease has been thoroughly studied, early obesity affecting approximately 50% of them during childhood has been somewhat neglected. It nevertheless represents a major health problem in these patients, and is associated to life-threatening complications including increasing risk of cardiovascular pathologies. Read More

Egypt Heart J 2017 Mar 15;69(1):85-88. Epub 2016 Mar 15.

Mssh, Saket, New Delhi 110017, India.

Mol Syndromol 2018 Feb 2;9(2):92-99. Epub 2018 Feb 2.

Laboratório de Medicina Genômica, Departamento de Genética Médica.

Mutations in the fibroblast growth factor receptor 3 gene () cause achondroplasia (ACH), hypochondroplasia (HCH), and thanatophoric dysplasia types I and II (TDI/TDII). In this study, we performed a genetic study of 123 Brazilian patients with these phenotypes. Mutation hotspots of the gene were PCR amplified and sequenced. Read More

Congenit Anom (Kyoto) 2018 Mar 14. Epub 2018 Mar 14.

Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan.

Thanatophoric dysplasia and achondroplasia are allelic disorders caused by a constitutively active mutation in the FGFR3 gene. Because thanatophoric dysplasia is a lethal disorder and achondroplasia is non-lethal, they need to be distinguished after ultrasound identification of fetal growth retardation with short limbs. Accordingly, we have developed a noninvasive prenatal test using cell-free fetal DNA in the maternal circulation to distinguish thanatophoric dysplasia and achondroplasia. Read More

Disabil Rehabil 2018 Mar 8:1-11. Epub 2018 Mar 8.

a Department of Medical Psychology , Center for Psychosocial Medicine, University Medical Center Hamburg-Eppendorf , Hamburg , Germany.

Background: This study describes the psychometric testing of the Achondroplasia Personal Life Experience Scale (APLES): a new disease- and functioning-specific health-related quality of life instrument for young people with achondroplasia, which was developed based on the International Classification of Functioning-Children and Youth Version.

Method: The qualitative analysis of focus group statements from German patients and parents using the International Classification of Functioning-Children and Youth Version yielded 59 items, which after cognitive debriefing were included in a pilot-test. Psychometric performance was cross-culturally examined in a field- and re-test in Germany and Spain. Read More

Clin Calcium 2018;28(3):381-388

Department of Bone and Mineral Research, Research Institute, Osaka Women's and Children's Hospital, Osaka Prefectural Hospital Organization, Japan.

Congenital skeletal dysplasias have been considered to be fundamentally untreatable diseases. However, molecular diagnosis by genetic testing has become more prevalent, and efforts are being made to develop novel therapies based on the pathogenesis. As treatments for osteogenesis imperfecta, in addition to anti-resorptive agents, neutralizing antibodies against sclerostin and transforming growth factor(TGF)-β and chemical chaperones can be beneficial. Read More

Int J Paleopathol 2018 03 14;20:65-71. Epub 2017 Dec 14.

The University of Western Ontario, Department of Anthropology, N6A-3K7, London, Canada; Leiden University, Faculty of Archaeology, Laboratory for Human Osteoarchaeology, Postbus 9514, 2300RA, Leiden, The Netherlands.

A 66 year-old woman with a disproportionate dwarfism and who bore seven children was discovered at the Middenbeemster archaeological site (The Netherlands). Three are perinates and show no macroscopic or radiological evidence for a FGFR3 mutation causing hypo-or achondroplasia. This mutation induces dysfunction of the growth cartilage, leading to abnormalities in the development of trabecular bone. Read More