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International Journal of Environmental... Feb 2022Regional odontodysplasia is a rare developmental disorder characterised by hypoplasia and hypomineralisation of enamel and dentin. Our systematic review aimed to... (Review)
Review
Regional odontodysplasia is a rare developmental disorder characterised by hypoplasia and hypomineralisation of enamel and dentin. Our systematic review aimed to organise the knowledge on localisation, symptomatology and treatment methods in patients with regional odontodysplasia based on case reports published in the databases PubMed, Scopus and Web of Science. Case reports were described in 28 different countries, considering 180 patients (including 91 females). Regional odontodysplasia occurs mainly in both deciduous and permanent dentition (66.1%). The affected teeth were observed more frequently in the maxilla (70.0%), especially on the left side (45.6%). The most common reported symptoms were ghost teeth, poorly developed buds, yellowish-brown colour of crowns and delayed eruption of permanent teeth in affected quadrants. The most popular treatment method was surgical treatment (78.6%) with subsequent prosthetic therapy (34.6%). Based on the review of cases, pathognomonic clinical and radiological signs can be found, however, it is difficult to reach a consensus on the choice of treatment method.
Topics: Bibliometrics; Dentition, Permanent; Female; Humans; Maxilla; Odontodysplasia; Radiography; Tooth, Deciduous
PubMed: 35162705
DOI: 10.3390/ijerph19031683 -
American Journal of Medical Genetics.... Jan 2022Pathogenic-activating variants of interferon induced with Helicase C domain 1 (IFIH1) cause Singleton-Merten (S-M) syndrome, which accompanies acro-osteolysis, loss of...
Pathogenic-activating variants of interferon induced with Helicase C domain 1 (IFIH1) cause Singleton-Merten (S-M) syndrome, which accompanies acro-osteolysis, loss of permanent teeth, and aortic calcification, as well as causing Aicardi-Goutières (A-G) syndrome, which shows progressive encephalopathy, spastic paraplegia, and calcification of basal ganglia. Recently, patients with overlapping syndromes presenting with features of S-M syndrome and A-G syndrome were reported. However, progression of clinical features of this condition has not been fully understood. We report a Japanese boy with a novel pathogenic IFIH1 variant who presented with clinical features of S-M syndrome and A-G syndrome.
Topics: Aortic Diseases; Autoimmune Diseases of the Nervous System; Dental Enamel Hypoplasia; Humans; Interferon-Induced Helicase, IFIH1; Interferons; Japan; Male; Metacarpus; Muscular Diseases; Nervous System Malformations; Odontodysplasia; Osteoporosis; Vascular Calcification
PubMed: 34453469
DOI: 10.1002/ajmg.a.62478 -
Biomolecules Aug 2021Melanoma differentiation-associated protein 5 (MDA5) is a crucial RIG-I-like receptor RNA helicase enzyme encoded by in humans. Single nucleotide polymorphisms in the...
Melanoma differentiation-associated protein 5 (MDA5) is a crucial RIG-I-like receptor RNA helicase enzyme encoded by in humans. Single nucleotide polymorphisms in the results in fatal genetic disorders such as Aicardi-Goutières syndrome and Singleton-Merten syndrome, and in increased risk of type I diabetes in humans. In this study, we chose four different amino acid substitutions of the MDA5 protein responsible for genetic disorders: MDA5, MDA5, MDA5, and MDA5 and analyzed their structural and functional relationships using molecular dynamic simulations. Our results suggest that the mutated complexes are relatively more stable than the wild-type MDA5. The radius of gyration, interaction energies, and intra-hydrogen bond analysis indicated the stability of mutated complexes over the wild type, especially MDA5 and MDA5. The dominant motions exhibited by the wild-type and mutant complexes varied significantly. Moreover, the betweenness centrality of the wild-type and mutant complexes showed shared residues for intra-signal propagation. The observed results indicate that the mutations lead to a gain of function, as reported in previous studies, due to increased interaction energies and stability between RNA and MDA5 in mutated complexes. These findings are expected to deepen our understanding of MDA5 variants and may assist in the development of relevant therapeutics against the disorders.
Topics: Aortic Diseases; Autoimmune Diseases of the Nervous System; Computational Biology; Dental Enamel Hypoplasia; Humans; Hydrogen Bonding; Interferon-Induced Helicase, IFIH1; Metacarpus; Molecular Conformation; Molecular Dynamics Simulation; Muscular Diseases; Mutant Proteins; Mutation; Mutation, Missense; Nervous System Malformations; Odontodysplasia; Osteoporosis; Phenotype; Principal Component Analysis; RNA; Thermodynamics; Vascular Calcification
PubMed: 34439917
DOI: 10.3390/biom11081251 -
Journal of Medical Genetics Mar 2022Singleton-Merten syndrome (SGMRT) is a rare immunogenetic disorder that variably features juvenile open-angle glaucoma (JOAG), psoriasiform skin rash, aortic...
BACKGROUND
Singleton-Merten syndrome (SGMRT) is a rare immunogenetic disorder that variably features juvenile open-angle glaucoma (JOAG), psoriasiform skin rash, aortic calcifications and skeletal and dental dysplasia. Few families have been described and the genotypic and phenotypic spectrum is poorly defined, with variants in (DExD/H-box helicase 58) being one of two identified causes, classified as SGMRT2.
METHODS
Families underwent deep systemic phenotyping and exome sequencing. Functional characterisation with in vitro luciferase assays and in vivo interferon signature using bulk and single cell RNA sequencing was performed.
RESULTS
We have identified a novel variant c.1529A>T p.(Glu510Val) that segregates with disease in two families with SGMRT2. Patients in these families have widely variable phenotypic features and different ethnic background, with some being severely affected by systemic features and others solely with glaucoma. JOAG was present in all individuals affected with the syndrome. Furthermore, detailed evaluation of skin rash in one patient revealed sparse inflammatory infiltrates in a unique distribution. Functional analysis showed that the variant is a dominant gain-of-function activator of interferon pathways in the absence of exogenous RNA ligands. Single cell RNA sequencing of patient lesional skin revealed a cellular activation of interferon-stimulated gene expression in keratinocytes and fibroblasts but not in neighbouring healthy skin.
CONCLUSIONS
These results expand the genotypic spectrum of DDX58-associated disease, provide the first detailed description of ocular and dermatological phenotypes, expand our understanding of the molecular pathogenesis of this condition and provide a platform for testing response to therapy.
Topics: DEAD Box Protein 58; Exanthema; Glaucoma, Open-Angle; Humans; Interferons; Metacarpus; Odontodysplasia; Receptors, Immunologic
PubMed: 33495304
DOI: 10.1136/jmedgenet-2020-107447 -
Arteriosclerosis, Thrombosis, and... Jan 2021Arterial calcification is a common phenomenon in the elderly, in patients with atherosclerosis or renal failure and in diabetes. However, when present in very young... (Review)
Review
Arterial calcification is a common phenomenon in the elderly, in patients with atherosclerosis or renal failure and in diabetes. However, when present in very young individuals, it is likely to be associated with an underlying hereditary disorder of arterial calcification. Here, we present an overview of the few monogenic disorders presenting with early-onset cardiovascular calcification. These disorders can be classified according to the function of the respective disease gene into (1) disorders caused by an altered purine and phosphate/pyrophosphate metabolism, (2) interferonopathies, and (3) Gaucher disease. The finding of arterial calcification in early life should alert the clinician and prompt further genetic work-up to define the underlying genetic defect, to establish the correct diagnosis, and to enable appropriate therapy.
Topics: Animals; Aortic Diseases; Arteries; Dental Enamel Hypoplasia; Gaucher Disease; Genetic Predisposition to Disease; Heredity; Humans; Metabolism, Inborn Errors; Metacarpus; Muscular Diseases; Odontodysplasia; Osteogenesis; Osteoporosis; Phenotype; Risk Assessment; Risk Factors; Vascular Calcification
PubMed: 33176451
DOI: 10.1161/ATVBAHA.120.315577 -
European Journal of Paediatric Dentistry Sep 2020Segmental odontomaxillary dysplasia is an uncommon nonhereditary growth disorder that affects the maxilla, gums and ipsilateral dentition. The disorder is diagnosed...
BACKGROUND
Segmental odontomaxillary dysplasia is an uncommon nonhereditary growth disorder that affects the maxilla, gums and ipsilateral dentition. The disorder is diagnosed mainly based on dental (over-retention of primary teeth, dental agenesis and diastemas) and bone findings (bone sclerosis, irregular trabeculation of immature bone and reduced maxillary sinus). This paper provides a case report.
CASE REPORT
A 5-year-old child with skin manifestations including hypertrichosis, facial erythema and pigmented nevus was diagnosed with type II segmental odontomaxillary dysplasia based on clinical, radiographic and histopathological analysis.
CONCLUSION
The skin findings can help with the suspicion of segmental odontomaxillary dysplasia, although the definitive diagnosis is typically established by a paediatric dentist based on clinical and radiological findings.
Topics: Child, Preschool; Diastema; Humans; Maxilla; Odontodysplasia; Skin Diseases; Tooth, Deciduous
PubMed: 32893658
DOI: 10.23804/ejpd.2020.21.03.14 -
Head and Neck Pathology Mar 2021Segmental odontomaxillary dysplasia (SOD) is a developmental condition of the middle and posterior maxilla featuring dysplastic bone overgrowth, dental abnormalities...
Segmental Ipsilateral Odontognathic Dysplasia (Mandibular Involvement in Segmental Odontomaxillary Dysplasia?) and Identification of PIK3CA Somatic Variant in Lesional Mandibular Gingival Tissue.
Segmental odontomaxillary dysplasia (SOD) is a developmental condition of the middle and posterior maxilla featuring dysplastic bone overgrowth, dental abnormalities and, occasionally, various homolateral cutaneous manifestations. Herein, we describe an individual with maxillary abnormality akin to SOD and associated ipsilateral segmental odontomandibular dysplasia. Also, the result of the evaluation of lesional mandibular gingival tissue for overgrowth-related gene variants is reported. An 8-year-old girl presented clinically with congenital maxillary and mandibular alveolar soft tissue enlargement in the area of the premolars. A panoramic radiograph revealed abnormal trabeculation essentially similar to SOD in the maxilla and mandible with congenitally missing maxillary and mandibular first and second premolars and mandibular canines. Diagnostic mandibular bone biopsy was performed and lesional mandibular gingival hyperplastic tissue was obtained for variant analysis of somatic overgrowth genes PIK3CA, AKT1, AKT3, GNAQ, GNA11, MTOR, PIK3R2. Cone beam computerized tomography (CBCT) disclosed osseous abnormalities on the left side of the maxilla and mandible and very mild osseous expansion in the mandible. Histologically, abnormal bone exhibiting prominent reversal lines was present and associated with fibrocollagenous tissue. Genomic DNA analysis disclosed PIK3CAc.1571G>A; pArg524Lys which was seen at a low mosaic level in the blood, indicating a post-zygotic change. Although this case may be a unique disorder, by sharing features with SOD, one can suggest the possibility of mandibular involvement in SOD. The presence of a PIK3CA variant may support the hypothesis that these segmental disorders could be part of the PIK3CA-related overgrowth spectrum.
Topics: Child; Class I Phosphatidylinositol 3-Kinases; Female; Gingival Hyperplasia; Humans; Mandible; Maxilla; Odontodysplasia
PubMed: 32500425
DOI: 10.1007/s12105-020-01185-5 -
International Journal of Molecular... Oct 2019The dental abnormalities are the typical features of many ectodermal dysplasias along with congenital malformations of nails, skin, hair, and sweat glands. However,...
The dental abnormalities are the typical features of many ectodermal dysplasias along with congenital malformations of nails, skin, hair, and sweat glands. However, several reports of non-syndromic/isolated tooth agenesis have also been found in the literature. The characteristic features of hypohidrotic ectodermal dysplasia (HED) comprise of hypodontia/oligodontia, along with hypohidrosis/anhidrosis, and hypotrichosis. Pathogenic variants in , , , and , cause the phenotypic expression of HED. Genetic alterations in and cause particularly non-syndromic/isolated oligodontia. In the current project, we recruited 57 patients of 17 genetic pedigrees (A-Q) from different geographic regions of the world, including Pakistan, Egypt, Saudi Arabia, and Syria. The molecular investigation of different syndromic and non-syndromic dental conditions, including hypodontia, oligodontia, generalized odontodysplasia, and dental crowding was carried out by using exome and Sanger sequencing. We have identified a novel missense variant (c.311G>A; p.Arg104His) in in three oligodontia patients of family A, two novel sequence variants (c.207delinsTT, p.Gly70Trpfs*25 and c.1300T>G; p.Try434Gly) in in three patients of family B and four patients of family C, respectively. To better understand the structural and functional consequences of missense variants in WNT10A and EDAR on the stability of the proteins, we have performed extensive molecular dynamic (MD) simulations. We have also identified three previously reported pathogenic variants (c.1076T>C; p.Met359Thr), (c.1133C>T; p.Thr378Met) and (c.594_595insC; Gly201Argfs*39) in in family D (four patients), E (two patients) and F (one patient), correspondingly. Presently, our data explain the genetic cause of 18 syndromic and non-syndromic tooth agenesis patients in six autosomal recessive and X-linked pedigrees (A-F), which expand the mutational spectrum of these unique clinical manifestations.
Topics: Ectodermal Dysplasia 1, Anhidrotic; Ectodysplasins; Edar Receptor; Humans; Molecular Dynamics Simulation; Mutation, Missense; Pedigree; Phenotype; Protein Stability; Protein Structure, Tertiary; Exome Sequencing; Wnt Proteins
PubMed: 31652981
DOI: 10.3390/ijms20215282 -
Head and Neck Pathology Mar 2020Regional odontodysplasia (RO) is a rare dental anomaly of unknown etiology that can affect both deciduous and permanent dentition. RO is characterized by severe...
Regional odontodysplasia (RO) is a rare dental anomaly of unknown etiology that can affect both deciduous and permanent dentition. RO is characterized by severe hypoplasia of enamel and dentin, and teeth affected are friable and more susceptible to caries and fractures. Most of the lesions occur in the anterior maxilla and correlation with clinical and radiographic features is essential to provide a correct diagnosis. The major criteria for diagnosis are predominantly based on radiography, which shows presence of large pulp chambers and a marked reduction in the radiopacity of enamel and dentin, making the distinction between these mineralized structures difficult. Early diagnosis is important to minimize future sequels and allow preventive or conservative treatment. The therapeutic approach of the RO should be based on the degree of severity of the anomaly and in the individual functional and aesthetic needs of each case. A classic case of RO affecting the maxilla is exemplified in this Sine Qua Non Radiology-Pathology article.
Topics: Child; Female; Humans; Maxilla; Odontodysplasia
PubMed: 30900210
DOI: 10.1007/s12105-019-01031-3