RESUMO
Dental agenesis is the most common developmental anomaly in humans and is frequently associated with several other oral abnormalities. Whereas the incidence of missing teeth may vary considerably depending on dentition, gender, and demographic or geographic profiles, distinct patterns of agenesis have been detected in the permanent dentition. These frequently involve the last teeth of a class to develop (I2, P2, M3) suggesting a possible link with evolutionary trends. Hypodontia can either occur as an isolated condition (non-syndromic hypodontia) involving one (80% of cases), a few (less than 10%) or many teeth (less than 1%), or can be associated with a systemic condition or syndrome (syndromic hypodontia), essentially reflecting the genetically and phenotypically heterogeneity of the condition. Based on our present knowledge of genes and transcription factors that are involved in tooth development, it is assumed that different phenotypic forms are caused by different genes involving different interacting molecular pathways, providing an explanation not only for the wide variety in agenesis patterns but also for associations of dental agenesis with other oral anomalies. At present, the list of genes involved in human non-syndromic hypodontia includes not only those encoding a signaling molecule (TGFA) and transcription factors (MSX1 and PAX9) that play critical roles during early craniofacial development, but also genes coding for a protein involved in canonical Wnt signaling (AXIN2), and a transmembrane receptor of fibroblast growth factors (FGFR1). Our objective was to review the current literature on the molecular mechanisms that are responsible for selective dental agenesis in humans and to present a detailed overview of syndromes with hypodontia and their causative genes. These new perspectives and future challenges in the field of identification of possible candidate genes involved in dental agenesis are discussed.
Assuntos
Anodontia/genética , Anodontia/classificação , Proteína Axina , Proteínas do Citoesqueleto/genética , Humanos , Fator de Transcrição MSX1/genética , Odontogênese/genética , Fator de Transcrição PAX9/genética , Fenótipo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Síndrome , Fator de Crescimento Transformador alfa/genéticaRESUMO
Premature fusion of the calvarial bones at the sutures, or craniosynostosis (CS), is a relatively common birth defect (1:2000-3000) frequently associated with limb deformity. Patients with CS may present oral defects, such as cleft soft palate, hypodontia, hyperdontia, and delayed tooth eruption, but also unusual associations of major dental anomalies such as taurodontism, microdontia, multiple dens invaginatus, and dentin dysplasia. The list of genes that are involved in CS includes those coding for the different fibroblast growth factor receptors and a ligand of ephrin receptors, but also genes encoding transcription factors, such as MSX2 and TWIST. Most of these genes are equally involved in odontogenesis, providing a pausible explanation for clinical associations of CS with dental agenesis or tooth malformations. On the basis of the present knowledge on genes and transcription factors that are involved in craniofacial morphogenesis, and from dental clinics of CS syndromes, the molecular mechanisms that control suture formation and suture closure are expected to play key roles in patterning events and development of teeth. The purpose of this article is to review and merge the recent advances in the field of suture research at the genetic and cellular levels with those of tooth development, and to apply them to the dental clinics of CS syndromes. These new perspectives and future challenges in the field of both dental clinics and molecular genetics, more in particular the identification of possible candidate genes involved in both CS and dental defects, are discussed.
Assuntos
Suturas Cranianas/fisiologia , Craniossinostoses/genética , Odontogênese/genética , Suturas Cranianas/metabolismo , Craniossinostoses/fisiopatologia , Proteínas de Ligação a DNA/genética , Efrinas/genética , Proteínas de Homeodomínio/genética , Humanos , Biologia Molecular , Proteínas Nucleares/genética , Odontogênese/fisiologia , Receptores de Fatores de Crescimento de Fibroblastos/genética , Anormalidades Dentárias/genética , Anormalidades Dentárias/fisiopatologia , Fatores de Transcrição/genética , Proteína 1 Relacionada a Twist/genéticaRESUMO
Histological and ultrastructural observations of dentin of two patients affected with rare types of type I collagen disorders are presented. In the first case, a homozygous nonsense mutation in ADAMTS2 (substitution of a codon for tryptophan by a stopcodon) causes type VIIC Ehlers-Danlos syndrome (EDS) with multiple tooth agenesis and focal dysplastic dentin defects. In the second case, a missense mutation in COL1A1 (substitution of arginine by cysteine) results in a type I EDS phenotype with clinically normal-appearing dentition. Tooth samples are investigated by using light microscopy (LM), transmission electron microscopy (TEM) and immunostaining for types I and III collagen, and tenascin. These are compared with samples from patients with types III and IV osteogenesis imperfecta (OI) in association with dentinogenesis imperfecta (DI), showing a consistently abnormal appearance of the dentin in all specimens, with variations being primarily those of degree of change. Similarities in histological changes include the alternating presence of normal and severe pathological areas in primary and secondary dentin, the latter being characterized by large canal-like structures in atubular areas. Ultrastructural evidence of pathological dentinogenesis include abnormal distribution, size and organization of collagen fibers, which may also be found in clinically unaffected teeth. The histological and ultrastructural changes seen can be explained on the basis of odontoblast dysfunction which may be secondary to the collagen defect, interfering with different levels of odontoblast cell function and intercellular communication. These observations on (ultra)structural dentin defects associated with the two novel gene mutations are the first ever reported.
Assuntos
Colágeno Tipo I/ultraestrutura , Dentina/ultraestrutura , Dentinogênese Imperfeita/genética , Osteogênese Imperfeita/genética , Colágeno Tipo I/genética , Dentina/patologia , Dentinogênese Imperfeita/patologia , Humanos , Microscopia Eletrônica , Mutação/genética , Osteogênese Imperfeita/patologia , Descoloração de Dente/genética , Descoloração de Dente/patologiaRESUMO
Seckel syndrome (SCKL) [OMIM Entry 210600] is a rare, autosomal recessive syndrome, characterized by severe intrauterine and postnatal growth retardation, microcephaly, mental retardation, and typical facial appearance with beaklike protrusion of the midface (bird-headed). Associated findings may include limb anomalies, dislocation of femoral heads, scoliosis, and gastrointestinal malformation. A 14-year-old boy is presented with brain hypoplasia, pachygyria, hydrocephaly, enamel hypoplasia and root dysplasia in the temporary dentition, and oligodontia, severe microdontia, and delayed eruption of the permanent dentition. The association of SCKL with the above unusual dental findings may represent a new phenotype.
Assuntos
Anormalidades Múltiplas , Anodontia , Hipoplasia do Esmalte Dentário , Desmineralização do Dente , Erupção Dentária , Adolescente , Anodontia/diagnóstico por imagem , Anodontia/patologia , Hipoplasia do Esmalte Dentário/diagnóstico por imagem , Hipoplasia do Esmalte Dentário/patologia , Dentina/anormalidades , Nanismo , Fácies , Humanos , Masculino , Fenótipo , Radiografia , Síndrome , Desmineralização do Dente/diagnóstico por imagem , Desmineralização do Dente/patologiaRESUMO
The follow-up history and oral findings in two brothers from consanguineous parents suggest that the association of dentinogenesis imperfecta (DI), delayed tooth eruption, mild mental retardation, proportionate short stature, sensorineural hearing loss and dysmorphic facies may represent a new syndrome with autosomal recessive inheritance. Histological examination of the dentin matrix of a permanent molar from one of the siblings reveals morphological similarities with defective dentinogenesis as presenting in patients affected with Osteogenesis Imperfecta (OI), a condition caused by deficiency of type I collagen. A number of radiographic and histological characteristics, however, are inconsistent with classical features of DI. These findings suggest that DI may imply greater genetical heterogeneity than currently assumed.
Assuntos
Dentinogênese Imperfeita , Perda Auditiva , Deficiência Intelectual , Estatura , Criança , Pré-Escolar , Consanguinidade , Dentinogênese Imperfeita/diagnóstico por imagem , Dentinogênese Imperfeita/patologia , Genes Recessivos , Humanos , Masculino , Radiografia , SíndromeRESUMO
A 13-year-old patient with dermatosparaxis (Ehlers-Danlos syndrome type VIIC), an autosomal recessive disorder of procollagen-I-N-proteinase, is presented. The oral findings comprise micrognathia, hypodontia, localized microdontia, opalescent tooth discoloration, root dysplasia, pulp obliteration, severe gingival hyperplasia, frontal open bite, and severe restriction of TMJ mobility. The reported anomalies suggest the need for expanding the present phenotypic spectrum. This is the first report on oral findings in the syndrome.
Assuntos
Síndrome de Ehlers-Danlos/patologia , Anormalidades da Boca/patologia , Anormalidades Dentárias/patologia , Adolescente , Feminino , Humanos , Anormalidades Maxilomandibulares/patologia , Transtornos da Articulação Temporomandibular/patologiaRESUMO
OBJECTIVE: The purpose of this study was to conduct a complete analysis of the oral abnormalities of patients with Marfan syndrome. STUDY DESIGN: Twenty three patients with Marfan syndrome and 69 healthy controls were studied. The subjects were screened for cariologic and periodontal alterations, as well as structural defects of enamel and dentin. Data analysis was performed by using the t test, the chi-square test, and regression models. RESULTS: Patients aged 0 to 17 years were significantly at risk for caries. Local hypoplastic enamel spots were more frequent in Marfan syndrome and could be related to caries history of the deciduous dentition. Root deformity, abnormal pulp shape, and pulpal inclusions were a frequent finding in patients with Marfan syndrome. Calculus and gingival indices were significantly higher in the study group as well. CONCLUSIONS: This study shows the importance of early diagnosis of oral anomalies and timely treatment of dental problems in Marfan syndrome. A series of therapeutic guidelines to be integrated in treatment strategies is proposed.