Chondrodysplasia

BACKGROUND: Mutations in PTH1R are associated with Jansen-type metaphyseal chondrodysplasia (JMC), Blomstrand osteochondrodysplasia (BOCD), Eiken syndrome, enchondroma, and primary failure of tooth eruption (PFE). Inheritance of the PTH1R gene can be either autosomal dominant or autosomal recessive, indicating the complexity of the gene. Our objective was to identify the phenotypic differences in members of a family with a novel PTH1R mutation. METHODS: The proband was a 13-year, 6-month-old girl presenting with short stature, abnormal tooth eruption, skeletal dysplasia, and midface hypoplasia...

Activating parathyroid hormone (PTH)/PTH-related Peptide (PTHrP) receptor (PTH1R) mutations causes Jansen's metaphyseal chondrodysplasia (JMC), a rare disease characterized by growth plate abnormalities, short stature, and PTH-independent hypercalcemia. Previously generated transgenic JMC mouse models, in which the human PTH1R allele with the H223R mutation ( H223R-PTH1R ) is expressed in osteoblasts via type Ia1 collagen or DMP1 promoters cause excess bone mass, while expression of the mutant allele via the type IIa1 collagen promoter results in only minor growth plate changes...

Achondroplasia, the most common chondrodysplasia in humans, is caused by one of two gain of function mutations localized in the transmembrane domain of fibroblast growth factor receptor 3 (FGFR3) leading to constitutive activation of FGFR3 and subsequent growth plate cartilage and bone defects. Phenotypic features of achondroplasia include macrocephaly with frontal bossing, midface hypoplasia, disproportionate shortening of the extremities, brachydactyly with trident configuration of the hand, and bowed legs...

Measurement of plasmalogens is useful for the biochemical diagnosis of rhizomelic chondrodysplasia punctata (RCDP) and is also informative for Zellweger spectrum disorders (ZSD). We have developed a test method for the simultaneous quantitation of C16:0, C18:0, and C018:1 plasmalogen (PG) species and their corresponding fatty acids (FAs) in dried blood spots (DBS) and erythrocytes (RBC) by using capillary gas chromatography-mass spectrometry. Normal reference ranges for measured markers and 10 calculated ratios were established by the analysis of 720 and 473 unaffected DBS and RBC samples, respectively...

The spontaneous mutation stubby (stb) in mice causes chondrodysplasia and male infertility due to impotence through autosomal recessive inheritance. In this study, we conducted linkage analysis to localize the stb locus within a 1.6 Mb region on mouse chromosome 2 and identified a nonsense mutation in Adamtsl2 of stb/stb mice. Histological analysis revealed disturbed endochondral ossification with a reduced hypertrophic chondrocyte layer and stiff skin with a thickened dermal layer. These phenotypes are similar to those observed in humans and mice with ADAMTSL2/Adamtsl2 mutations...

Previous studies showed that chondrodysplasia has intrauterine origin. Although prenatal acetaminophen exposure (PAcE) can cause nervous and reproductive abnormalities in offspring, its effect on cartilage is uninvestigated. Herein, mice were treated with different doses and courses of acetaminophen at various gestational stages (100 or 400 mg/kg∙d on gestational days 10-12 (GD10-12), 400 mg/kg∙d on GD12 or GD15-17) based on clinical administration and conversion between humans and mice...

UNLABELLED: SCHMID metaphyseal chondrodysplasia is a rare cause of short stature with a good prognosis regarding other types of chondrodysplasia in reason of the normal integrity of the growth plate. CASE PRESENTATION: The authors present a rare case of 4-year-2-month-old boy referred to our Unit for harmonious short stature, he had a waddling gait, subtle micromelia, and hyperlordosis, no special facies. CLINICAL DISCUSSION: The skeletal scan made the diagnosis of SCHMID metaphyseal chondrodysplasia...

Carbohydrate sulfotransferases (CHST) catalyse the biosynthesis of proteoglycans that enable physical interactions and signalling between different neighbouring cells in physiological and pathological states. The study aim was to provide an overview of emerging diagnostic and prognostic applications of CHST. PubMed database search was conducted using the keywords "carbohydrate sulfotransferase" together with appropriate inclusion and exclusion criteria, whereby 41 publications were selected. Additionally, 40 records on CHST genetic and biochemical properties were hand-picked from UniProt, GeneCards, InterPro, and neXtProt databases...

Chondrodysplasia punctata (CDP) is a rare congenital syndrome characterized by aberrant, punctate deposition of calcium during endochondral bone formation, resulting in the characteristic finding of epiphyseal stippling on radiographs. While otolaryngologic manifestations such as nasomaxillary hypoplasia and mixed hearing loss are common, tracheobronchial calcification occurs rarely in neonates with CDP. The management of CDP-related airway stenosis is complex and there is limited literature pertaining to outcomes of airway interventions...

We present a comprehensive review dealing with rare genetic skeletal disorders. More than 400 entities are included in the latest classification. The most severe or lethal phenotypes are identifiable in the prenatal period and the pregnancy can be terminated. Perinatal autopsy and posmortem X-rays are crucial in providing a definitive diagnosis. The number of cases confirmed by genetic testing is increasing. We report our own experience with genetic skeletal disorders based on 41 illustrative fetal and neonatal cases which we encountered over a 10-year period...

Diastrophic dysplasia (DTD) is a recessive chondrodysplasia caused by pathogenic variants in the SLC26A2 gene encoding for a cell membrane sulfate/chloride antiporter crucial for sulfate uptake and glycosaminoglycan (GAG) sulfation. Research on a DTD animal model has suggested possible pharmacological treatment approaches. In view of future clinical trials, the identification of non-invasive biomarkers is crucial to assess the efficacy of treatments. Urinary GAG composition has been analyzed in several metabolic disorders including mucopolysaccharidoses...

There is evidence to suggest that microRNA-140-5p (miR-140), which acts as a suppressor, is often elevated and has a role in various malignancies. Nevertheless, neither the function nor the mechanisms in chondrocytes linked with bone disorders, e.g., tibial dyschondroplasia (TD), have been satisfactorily established. The purpose of this study was to look into the role of microRNA-140-5p (miR-140) and its interaction with HDAC4 in chondrocytes, as well as the implications for tibial dyschondroplasia (TD), with a particular focus on the relationship between low miR-140 expression and poor pathologic characteristics, as well as its physiological effects on chondrocyte growth, differentiation, and chondrodysplasia...

OBJECTIVE: To analyze the clinical features and genotype of a child with Schmid type metaphyseal chondrodysplasia. METHODS: Clinical data of the child and her parents was collected. The child was subjected to high-throughput sequencing, and candidate variant was verified by Sanger sequencing of her family members. RESULTS: Whole exome sequencing revealed that the child has harbored a heterozygous c.1772G>A (p.C591Y) variant of the COL10A1 gene, which was not found in either of her parents...

Rhizomelic chondrodysplasia punctata (RCDP) is a rare disorder (~1 in 100,000 live births) of faulty plasmalogen biosynthesis and defective peroxisomal metabolism. RCDP type 2 is specifically caused by glyceronephosphate O-acyltransferase ( GNPAT ) gene mutations and is inherited as an autosomal recessive trait. The disorder is characterized by skeletal abnormalities, distinctive facial features, intellectual disability, and respiratory distress. The case report describes a newborn baby with a dysmorphic facial appearance and skeletal abnormalities who was admitted to neonatal intensive care with respiratory distress...

Motile and non-motile cilia play critical roles in mammalian development and health. These organelles are composed of a 1000 or more unique proteins, but their assembly depends entirely on proteins synthesized in the cell body and transported into the cilium by intraflagellar transport (IFT). In mammals, malfunction of non-motile cilia due to IFT dysfunction results in complex developmental phenotypes that affect most organs. In contrast, disruption of motile cilia function causes subfertility, disruption of the left-right body axis, and recurrent airway infections with progressive lung damage...

BACKGROUND AND OBJECTIVES: Cartilage-hair hypoplasia (CHH) is a rare chondrodysplasia with associated primary immunodeficiency. The aim of this cross-sectional study was to examine oral health indicators in individuals with CHH. METHODS: In total, 23 individuals with CHH, aged between 4.5 and 70 years, and 46 controls aged between 5 and 76 years were clinically examined for periodontal disease, presence of oral mucosal lesions, tooth decay, masticatory system function, and malocclusions...

Mutations in a common extracellular domain of fibroblast growth factor receptor (FGFR)-2 isoforms (type IIIb and IIIc) cause craniosynostosis syndrome and chondrodysplasia syndrome. FGF10, a major ligand for FGFR2-IIIb and FGFR1-IIIb, is a key participant in the epithelial-mesenchymal interactions required for morphogenetic events. FGF10 also regulates preadipocyte differentiation and early chondrogenesis in vitro, suggesting that FGF10-FGFR signaling may be involved in craniofacial skeletogenesis in vivo. To test this hypothesis, we used a tet-on doxycycline-inducible transgenic mouse model (FGF10 Tg) to overexpress Fgf10 from embryonic day 12...

PURPOSE: Plasmalogens (Plgs) are highly abundant lipids in the retina, and their deficiency leads to severe abnormalities during eye development. The first acylation step in the synthesis of Plgs is catalyzed by the enzyme glyceronephosphate O-acyltransferase (GNPAT), which is also known as dihydroxyacetone phosphate-acyltransferase (EC 2.3.1.42). GNPAT deficiency produces rhizomelic chondrodysplasia punctata type 2, a genetic disorder associated with developmental ocular defects. Despite the relevance of retinal Plgs, our knowledge of the mechanisms that regulate their synthesis, and the role of GNPAT during eye development is limited...

Recombinant human growth hormone is a classical therapeutic drug for children with short stature. In recent years, as the mechanism of growth in children has been further explored, growth-promoting therapies other than growth hormone have made great progress. Recombinant human insulin-like growth factor (IGF)-1 is the main treatment for primary IGF-1 deficiency, and C-type natriuretic peptide (CNP) offers a therapeutic option for children with short stature due to chondrodysplasia. Growth hormone-releasing peptide analogues stimulate growth hormone release and may be used for growth-promoting therapy...

INTRODUCTION: Murk Jansen metaphyseal chondrodysplasia is an extremely rare form of skeletal dysplasia. It is caused by the mutation in PTH1R gene (1). MATERIALS: A 13 year old boy presented with history of progressive bowing of both legs since 5 years of age. He had no history of development delay, seizures, renal stones or abdominal distension. On examination, he was having prominent upper face, prominent tip of nose, long philtrum, small mandible and severe bowing of legs with deformed knee joint...