Isolated dentinogenesis imperfecta: Novel DSPP variants and insights on genetic counselling.

OBJECTIVE: Dentinogenesis imperfecta (DI) is an inherited dentin defect and may be isolated or associated with disorders such as osteogenesis imperfecta, odontochondrodysplasia Ehler-Danlos and others. Isolated DI is caused mainly by pathogenic variants in DSPP gene and around 50 different variants have been described in this gene. Herein, we report on 19 patients from two unrelated Egyptian families with isolated DI. Additionally, we focused on genetic counselling of the two families. MATERIALS AND METHODS: The patients were examined clinically and dentally. Panoramic X-rays were done to some patients. Whole exome sequencing (WES) and Sanger sequencing were used. RESULTS: WES revealed two new nonsense variants in DSPP gene, c.288T > A (p.Tyr96Ter) and c.255G > A (p.Trp85Ter). Segregation analysis by Sanger sequencing confirmed the presence of the first variant in all affected members of Family 1 while the second variant was confirmed to be de novo in the patient of Family 2. CONCLUSIONS AND CLINICAL RELEVANCE: Our study extends the number of DSPP pathogenic variants and strengthens the fact that DSPP is the most common DI causative gene irrespective of patients' ethnicity. In addition, we provide insights on genetic counseling issues in patients with inherited DSPP variants taking into consideration the variable religion, culture and laws in our society.

The Role of DSPP in Dentine Formation and Hereditary Dentine Defects.

The dentine sialophosphoprotein (DSPP) gene is the only identified causative gene for dentinogenesis imperfecta type 2 (DGI-II), dentinogenesis imperfecta type 3 (DGI-III) and dentine dysplasia type 2 (DD-II). These three disorders may have similar molecular mechanisms involved in bridging the DSPP mutations and the resulting abnormal dentine mineralisation. The DSPP encoding proteins DSP (dentine sialoprotein) and DPP (dentine phosphoprotein) are positive regulators of dentine formation and perform a function during dentinogenesis. The present review focused on the recent findings and viewpoints regarding the relationship between DSPP and dentinogenesis as well as mineralisation from multiple perspectives, involving studies relating to spatial structure and tissue localisation of DSPP, DSP and DPP, the biochemical characteristics and biological function of these molecules, and the causative role of the proteins in phenotypes of the knockout mouse model and in hereditary dentine defects.

[Recognition on dentin dysplasia type â ¡].

Dentin dysplasia type Ⅱ (DD-Ⅱ) is a subtype of hereditary dentin disorders. The dentin sialophosphoprotein (DSPP) gene has been revealed to be the causative gene, whose mutations could affect the normal tooth development process. The lesions involve both deciduous and permanent dentition, mainly manifested as tooth discoloration, attrition and even the subsequent malocclusion. If not treated in time, it will significantly affect the physical and psychological health of patients. The disease is difficult to be diagnosed in clinic accurately as its low incidence and hidden manifestations. The present article aims to discuss the clinical and radiographic characteristics, diagnosis, treatment of DD-Ⅱ, in order to improve the overall understanding on DD-Ⅱ for clinicians.

Hereditary dentin defects with systemic diseases.

OBJECTIVE: This review aimed to summarize recent progress on syndromic dentin defects, promoting a better understanding of systemic diseases with dentin malformations, the molecules involved, and related mechanisms. SUBJECTS AND METHODS: References on genetic diseases with dentin malformations were obtained from various sources, including PubMed, OMIM, NCBI, and other websites. The clinical phenotypes and genetic backgrounds of these diseases were then summarized, analyzed, and compared. RESULTS: Over 10 systemic diseases, including osteogenesis imperfecta, hypophosphatemic rickets, vitamin D-dependent rickets, familial tumoral calcinosis, Ehlers-Danlos syndrome, Schimke immuno-osseous dysplasia, hypophosphatasia, Elsahy-Waters syndrome, Singleton-Merten syndrome, odontochondrodysplasia, and microcephalic osteodysplastic primordial dwarfism type II were examined. Most of these are bone disorders, and their pathogenic genes may regulate both dentin and bone development, involving extracellular matrix, cell differentiation, and metabolism of calcium, phosphorus, and vitamin D. The phenotypes of these syndromic dentin defects various with the involved genes, part of them are similar to dentinogenesis imperfecta or dentin dysplasia, while others only present one or two types of dentin abnormalities such as discoloration, irregular enlarged or obliterated pulp and canal, or root malformation. CONCLUSION: Some specific dentin defects associated with systemic diseases may serve as important phenotypes for dentists to diagnose. Furthermore, mechanistic studies on syndromic dentin defects may provide valuable insights into isolated dentin defects and general dentin development or mineralization.

Identification of DSPP novel variants and phenotype analysis in dentinogenesis dysplasia Shields type II patients.

OBJECTIVES: To investigate the genetic causes and teeth characteristics of dentin dysplasia Shields type II(DD-II) in three Chinese families. MATERIALS AND METHODS: Data from three Chinese families affected with DD-II were collected. Whole-exome sequencing (WES) and whole-genome sequencing (WGS) were conducted to screen for variations, and Sanger sequencing was used to verify mutation sites. The physical and chemical characteristics of the affected teeth including tooth structure, hardness, mineral content, and ultrastructure were investigated. RESULTS: A novel frameshift deletion mutation c.1871_1874del(p.Ser624fs) in DSPP was found in families A and B, while no pathogenic mutation was found in family C. The affected teeth's pulp cavities were obliterated, and the root canals were smaller than normal teeth and irregularly distributed comprising a network. The patients' teeth also had reduced dentin hardness and highly irregular dentinal tubules. The Mg content of the teeth was significantly lower than that of the controls, but the Na content was obviously higher than that of the controls. CONCLUSIONS: A novel frameshift deletion mutation, c.1871_1874del (p.Ser624fs), in the DPP region of the DSPP gene causes DD-II. The DD-II teeth demonstrated compromised mechanical properties and changed ultrastructure, suggesting an impaired function of DPP. Our findings expand the mutational spectrum of the DSPP gene and strengthen the understanding of clinical phenotypes related to the frameshift deletion in the DPP region of the DSPP gene. CLINICAL RELEVANCE: A DSPP mutation can alter the characteristics of the affected teeth, including tooth structure, hardness, mineral content, and ultrastructure.

AAV6-Mediated Gene Therapy Prevents Developmental Dentin Defects in a Dentinogenesis Imperfecta Type â ¢ Mouse Model.

Dentin is a major type of hard tissue of teeth and plays essential roles for normal tooth function. Odontoblasts are responsible for dentin formation. Mutations or deficiency in various genes affect the differentiation of odontoblasts, leading to irreversible dentin developmental defects in animals and humans. Whether such dentin defects can be reversed by gene therapy for odontoblasts remains unknown. In this study, we compare the infection efficiencies of six commonly used adeno-associated virus (AAV) serotypes (AAV1, AAV5, AAV6, AAV8, AAV9, and AAVDJ) in cultured mouse odontoblast-like cells (OLCs). We show that AAV6 serotype infects OLCs with the highest efficiency among the six AAVs. Two cellular receptors, which are able to recognize AAV6, AAV receptor (AAVR), and epidermal growth factor receptor (EGFR), are strongly expressed in the odontoblast layer of mouse teeth. After local administration to mouse molars, AAV6 infects the odontoblast layer with high efficiency. Furthermore, AAV6-Mdm2 was successfully delivered to teeth and prevents the defects in odontoblast differentiation and dentin formation in Mdm2 conditional knockout mice (a mouse model of dentinogenesis imperfecta type Ⅲ). These results suggest that AAV6 can serve as a reliable and efficient vehicle for gene delivery to odontoblasts through local injection. In addition, human OLCs were also successfully infected by AAV6 with high efficiency, and both AAVR and EGFR are strongly expressed in the odontoblast layer of extracted human developing teeth. These findings suggest that AAV6-mediated gene therapy through local injection may be a promising treatment approach for hereditary dentin disorders in humans.

[Mutation of dentin sialophosphoprotein and hereditary malformations of dentin].

The classification as well as the clinical manifestations of hereditary malformations of dentin are of great concern and have been deeply elucidated. The understanding of its genetic basis also increases progressively. Dentin sialophosphoprotein (DSPP) is the pathogenic gene of dentinogenesis imperfecta type Ⅱ, dentinogenesis imperfecta type Ⅲ and dentin dysplasia type Ⅱ. In this article, the classification of DSPP mutations as well as the resultant dysfunction of the mutant DSPP are summarized respectively and the corresponding clinical manifestations are analyzed. This work will provide a reference for the diagnosis and treatment of hereditary malformations of dentin.

A novel DSPP frameshift mutation causing dentin dysplasia type 2 and disease management strategies.

The present study aims to investigate the mutation in a Chinese family with dentin dysplasia type II (DD-II) and to summarize mutation hotspots, clinical manifestations, and disease management strategies. Phenotype analysis, clinical intervention, mutation screening, and cosegregation analysis within the enrolled family were performed. A summary of the reported mutations in the dentin phosphoprotein (DPP) region of dentin sialophosphoprotein (DSPP) was analyzed. Pathogenicity prediction analysis of the physical properties and function of DSPP variants was performed by bioinformatic processing. Clinical management strategies are discussed. A novel pathogenic mutation (c.2035delA) in the DPP region of DSPP was identified, which was cosegregated in the family. The immature permanent teeth of patients with DD-II presented with X-shaped root canal phenotypes. Most of the identified mutations for DD-II were clustered in the DPP region between nucleotides 1686-2134. Points of differential diagnosis, clinical interventions, and management strategies are proposed. This study revealed a novel DSPP frameshift mutation and presented new clinical features of DD-II. The locus involving nucleotides 1686-2134 of DSPP may represent a mutational hotspot for the disease. Appropriate management of DD-II at different stages is important to avoid the development of secondary dental lesions.

Tratamiento integral de una adolescente con dentinogénesis imperfecta tipo I / Comprehensive treatment of an adolescent with type I dentinogenesis imperfecta

La dentinogénesis imperfecta (DI) es un desorden hereditario de carácter autosómico dominante, que se origina durante la etapa de histodiferenciación en el desarrollo dental y altera la formación de la denti-na. Se considera una displasia dentinaria que puede afectar ambas denticiones con una incidencia de 1 en 6000 a 8000 nacimientos. El tratamiento del pa-ciente con DI es complejo y multidisciplinario, supone un desafío para el odontólogo, ya que por lo general están involucradas todas las piezas dentarias y afec-ta no solo la salud buco dental sino el aspecto emo-cional y psicológico de los pacientes. Objetivo: des-cribir el tratamiento integral y rehabilitador realiza-do en una paciente adolescente con diagnóstico de DI tipo I. Relato del caso: Paciente de sexo femenino de 14 años, que concurrió en demanda de atención a la Cátedra de Odontología Integral Niños de la FOU-BA derivada del Hospital "Prof. Dr. Juan P. Garrahan" con diagnóstico de osteogénesis imperfecta tipo III (OI). Nunca recibió atención odontológica y el motivo de consulta fue la apariencia estética de sus piezas dentarias. Se realizó el examen clínico y radiográfico arrojando el diagnóstico de DI tipo I asociada a OI. Conclusión: El tratamiento rehabilitador de la DI tipo I en los pacientes en crecimiento y desarrollo debe estar dirigido a intervenir de manera integral y tem-prana para resolver la apariencia estética y funcio-nal, evitar las repercusiones sociales y emocionales y acompañar a los pacientes y sus familias (AU)

Dentinogenesis imperfecta (DI) is an autosomal dominant inherited disorder that originates during the histodifferentiation stage of tooth development and alters dentin formation. It is considered a den-tin dysplasia that can affect both dentitions with an incidence of 1 in 6000 to 8000 births. The treatment of patients with DI is complex and multidisciplinary, it is a challenge for the dentist, since in general all the teeth are involved and it affects not only oral health but also the emotional and psychological aspect of the patients. Objective: To describe the comprehen-sive and rehabilitative treatment carried out in an adolescent patient with a diagnosis of DI type I. Case report: A 14-year-old female patient, who required dental attention at the Department of Pediatric Den-tistry of FOUBA and was referred from the Hospital "Prof. Dr. Juan P. Garrahan" with a diagnosis of os-teogenesis imperfecta type III (OI). The patient never received dental care and the reason for consultation was esthetic appearance of her teeth. A clinical and radiographic examination was performed, resulting in a diagnosis of DI type I associated with OI. Conclu-sion: Rehabilitative treatment of DI in growing and developing patients will be aimed at early and com-prehensive intervention to resolve esthetic and func-tional appearance, avoid social and emotional reper-cussions and accompany patients and their families (AU)

A Review of Dentinogenesis Imperfecta and Primary Dentin Disorders in Dogs.

This review describes the clinical, radiographic and histologic characteristics of dentinogenesis imperfecta diagnosed in two unrelated young dogs without evidence of concurrent osteogenesis imperfecta. The dentition was noted to have generalized coronal discoloration ranging from grey-blue to golden brown. Clinical pulp exposure, coronal wear and fractures were observed as was radiographic evidence of endodontic disease, thin dentin walls or dystrophic obliteration of the pulp canal. The enamel was severely affected by attrition and abrasion despite histologically normal areas; loss was most likely due to poor adherence or support by the underlying abnormal dentin. Histologically, permanent and deciduous teeth examined showed thin, amorphous dentin without organized dentin tubules and odontoblasts had dysplastic cell morphology. Primary dentin disorders, including dentinogenesis imperfecta and dentin dysplasia, have been extensively studied and genetically characterized in humans but infrequently reported in dogs. Treatment in human patients is aimed at early recognition and multi-disciplinary intervention to restore and maintain normal occlusion, aesthetics, mastication and speech. Treatment in both humans and canine patients is discussed as is the documented genetic heritability of primary dentin disorders in humans.

Interdisciplinary Management of a Patient with Dentinogenesis Imperfecta Type II Using a Combination of CAD-CAM and Analog Techniques: A Clinical Report.

Type II dentinogenesis imperfecta is an autosomal dominant condition that affects dentin which increases the complexity of the predictability of restorative treatment. Computer-aided design and computer-aided manufacturing (CAD-CAM) technologies permit the creation of highly accurate devices and dental prostheses that simplify the planning and execution of advanced implant surgery and full-mouth rehabilitation. This clinical report presents the interdisciplinary management of a 20-year-old male with dentinogenesis imperfecta type II. In this article, a combination of analog and CAD-CAM technologies were used to fabricate devices that aided planning, assisted intermaxillary fixation and implant placement, served as interim prostheses, and permitted the accurate establishment of esthetics and occlusion of the definitive full-arch prostheses.

The Modified Shields Classification and 12 Families with Defined DSPP Mutations.

Mutations in Dentin Sialophosphoprotein (DSPP) are known to cause, in order of increasing severity, dentin dysplasia type-II (DD-II), dentinogenesis imperfecta type-II (DGI-II), and dentinogenesis imperfecta type-III (DGI-III). DSPP mutations fall into two groups: a 5'-group that affects protein targeting and a 3'-group that shifts translation into the −1 reading frame. Using whole-exome sequence (WES) analyses and Single Molecule Real-Time (SMRT) sequencing, we identified disease-causing DSPP mutations in 12 families. Three of the mutations are novel: c.53T>C/p.(Val18Ala); c.3461delG/p.(Ser1154Metfs*160); and c.3700delA/p.(Ser1234Alafs*80). We propose genetic analysis start with WES analysis of proband DNA to identify mutations in COL1A1 and COL1A2 causing dominant forms of osteogenesis imperfecta, 5'-DSPP mutations, and 3'-DSPP frameshifts near the margins of the DSPP repeat region, and SMRT sequencing when the disease-causing mutation is not identified. After reviewing the literature and incorporating new information showing distinct differences in the cell pathology observed between knockin mice with 5'-Dspp or 3'-Dspp mutations, we propose a modified Shields Classification based upon the causative mutation rather than phenotypic severity such that patients identified with 5'-DSPP defects be diagnosed as DGI-III, while those with 3'-DSPP defects be diagnosed as DGI-II.

Mouse Dspp frameshift model of human dentinogenesis imperfecta.

Non-syndromic inherited defects of tooth dentin are caused by two classes of dominant negative/gain-of-function mutations in dentin sialophosphoprotein (DSPP): 5' mutations affecting an N-terminal targeting sequence and 3' mutations that shift translation into the - 1 reading frame. DSPP defects cause an overlapping spectrum of phenotypes classified as dentin dysplasia type II and dentinogenesis imperfecta types II and III. Using CRISPR/Cas9, we generated a Dspp-1fs mouse model by introducing a FLAG-tag followed by a single nucleotide deletion that translated 493 extraneous amino acids before termination. Developing incisors and/or molars from this mouse and a DsppP19L mouse were characterized by morphological assessment, bSEM, nanohardness testing, histological analysis, in situ hybridization and immunohistochemistry. DsppP19L dentin contained dentinal tubules but grew slowly and was softer and less mineralized than the wild-type. DsppP19L incisor enamel was softer than normal, while molar enamel showed reduced rod/interrod definition. Dspp-1fs dentin formation was analogous to reparative dentin: it lacked dentinal tubules, contained cellular debris, and was significantly softer and thinner than Dspp+/+ and DsppP19L dentin. The Dspp-1fs incisor enamel appeared normal and was comparable to the wild-type in hardness. We conclude that 5' and 3' Dspp mutations cause dental malformations through different pathological mechanisms and can be regarded as distinct disorders.

Dentinogenesis imperfecta type 2: a case report.

Dentinogenesis imperfecta type 2, also referred to as Capdepont teeth and hereditary opalescent dentin, is a rare hereditary dysplasia affecting the dentin that occurs during the histodifferentiation stage of tooth development. The resulting brownish gray opalescent hue creates an unesthetic appearance. This form of dentin anomaly occurs in approximately 1 in 8000 individuals in the United States. Teeth affected by hereditary dentin dysplasia chip easily, even under normal masticatory forces; however, as a result of underlying sclerotic dentin formation and obliteration of pulp chambers in response to attrition, these teeth are not hypersensitive. This case report describes this rare anomaly in a 27-year-old woman, whose discolored teeth were restored with ceramic laminate veneers.

Combined exome sequencing and deep phenotyping in highly selected fetuses with skeletal dysplasia during the first and second trimesters improves diagnostic yield.

OBJECTIVE: To investigate the genetic etiology of skeletal dysplasia in highly selected fetuses during the first and second trimesters using deep phenotyping and exome sequencing (ES). METHOD: Fetuses with short femurs were identified using the established prenatal diagnostic approach. A multidisciplinary team reviewed fetal phenotypic information (prenatal ultrasound findings, fetal postmortem, and radiographs) in a cohort of highly selected fetuses with skeletal dysplasia during the first and second trimesters. The affected families underwent multiplatform genetic tests. RESULTS: Of the 27 affected fetuses, 21 (77.8%) had pathogenic or potential pathogenic variations in the following genes: COL1A1, FGFR3, COL2A1, COL1A2, FLNB, DYNC2LI1, and TRIP11. Two fetuses had compound heterozygous mutations in DYNC2LI1 and TRIP11, respectively, and the other 19 carried de novo autosomal dominant variants. Novel variants were identified in COL1A1, COL2A1, COL1A2, DYNC2LI1, and TRIP11 in 11 fetuses. We also included the first description of the phenotype of odontochondrodysplasia in a prenatal setting. CONCLUSIONS: ES or panel sequencing offers a high diagnostic yield for fetal skeletal dysplasia during the first and second trimesters. Comprehensive and complete phenotypic information is indispensable for genetic analysis and the expansion of genotype-phenotype correlations in fetal skeletal abnormalities.

Phenotypic features of dentinogenesis imperfecta associated with osteogenesis imperfecta and COL1A2 mutations.

OBJECTIVE: Dentinogenesis imperfecta (DI) requires dental treatment. This study investigated the characteristics of DI teeth associated with osteogenesis imperfecta (OI) and COL1A2 mutations. STUDY DESIGN: Whole exome and Sanger sequencing were performed. Three primary teeth (called "OIDI teeth") obtained from 3 unrelated COL1A2 patients were investigated and compared with 9 control teeth from age-matched healthy individuals using colorimetry, micro-computed tomography, Knoop microhardness, energy dispersive X-ray spectroscopy, scanning electron microscopy, and histology. RESULTS: All patients were identified with heterozygous glycine substitutions in COL1A2. The COL1A2 mutations, c.1531G>T and c.2027G>T, were de novo, whereas c.3106G>C was inherited. OIDI1, 2, and 3 teeth had a substantial decrease in dentin microhardness and lightness. OIDI2 enamel microhardness was significantly reduced, whereas OIDI1 and 3 had enamel microhardness comparable to that of control individuals. The OIDI1 pulp cavity was large; OIDI2 was narrow; and OIDI3 was obliterated. OIDI1 and 3 had significantly higher carbon levels than those in control individuals. Numerous ectopic calcified masses, sparse and obstructed dentinal tubules, dentin holes, and collagen disorientation were observed. CONCLUSIONS: OIDI teeth had reduced lightness and variable pulp morphology. Weak dentin, mineral disproportion, and abnormal ultrastructure could contribute to the brittleness of OIDI teeth and adhesive restoration failure. Here, we expand the phenotypic spectrum of COL1A2 mutations and raise awareness among dentists seeing patients with OI.

Tratamiento integral y control a 12 años de paciente con Dentinogénesis Imperfecta tipo I / Manejo clínico e seguimento de 12 anos em paciente com Dentinogênese Imperfeita tipo I / Clinical management and 12 years follow up in a patient with Dentinogenesis Imperfecta type I

La Dentinogénesis Imperfecta es una anomalía dentaria determinada genéticamente y caracterizada clínicamente por una apariencia ámbar opalescente de la dentina. Se presenta la resolución clínica, con seguimiento y control a 12 años de un paciente de 3 años de edad al momento de la consulta, con diagnóstico de Dentinogénesis Imperfecta tipo I asociada a Osteogénesis Imperfecta tipo IB. La identificación temprana de esta entidad y el tratamiento oportuno y multidisciplinario, contribuyen a mejorar el pronóstico de la misma.

Dentinogênese Imperfeita é uma anormalidade dentária geneticamente determinada, caracterizada clinicamente pela aparência opalescente e translúcida da dentina. Manejo clínico e seguimento de 12 anos são relatados, em um paciente de 3 anos com Dentinogênese Imperfeita tipo I associado à Osteogenesis Imperfecta tipo IB. O diagnóstico precoce.

Dentinogenesis Imperfecta is a geneti-cally determinated dental abnormality, characterized clinically by opalescent and translucent appearance of the den-tin. Clinical management and a 12 years follow up are reported, in a 3 years old patient with Dentinogenesis Imperfecta type I associated with Osteogenesis Im-perfecta type IB. The earlier diagnosis and the opportune and multidisciplinary treatment, led to improve the prognosis.

Dentinogénesis imperfecta tipo II: Reporte de caso de dos pacientes de un mismo grupo familiar / Dentinogenesis imperfecta type II: Case report of two patients from the same family group

Resumen Introducción: La dentinogenesis imperfecta (DI) se ha definido como una alteración hereditaria de carácter autosómico dominante, que se origina durante la etapa de histodiferenciación en el desarrollo dental, es un tipo de displasia del tejido dentinario que afecta la estructura de la dentina de una o ambas denticiones. Las complicaciones de la DI tiene un fuerte impacto en la calidad de vida de los pacientes ya que la parte funcional, estética y fonética se suelen encontrar afectadas y representan un reto importante para el tratante. El diagnóstico precoz y el tratamiento adecuado son necesarios para lograr mejores resultados funcionales y estéticos, minimizar las deficiencias nutricionales y trastornos psicosociales, permitiendo así mejorarla calidad de vida de la persona. Objetivo: Determinar el tipo de dentinogenesis, la relación familiar, y las características clínicas de cada paciente. Métodos: Acuden a la clínica de Odontología de la Universidad Católica de Cuenca, dos Hermanos procedentes de la ciudad de Cuenca-Ecuador, de las edades de 5 y 6 años respectivamente, por presentar múltiples lesiones cariosas, se puede evidencia destrucción generalizada del remanente coronario y pérdida prematura de las piezas dentales. Después de realizar el diagnóstico clínico y radiográfico, historia familiar, se estableció el diagnóstico de dentinogenesis imperfecta tipo II. Conclusión: es de gran importancia el diagnóstico oportuno y temprano de la dentinogenesis imperfecta para un tratamiento adecuado, debido a que la DI, afecto de mayormente a la dentición temporal, es fundamental las visitas al odontólogo, ya que este podrá diagnosticar tempranamente la patología y evitar grandes daños.

Abstract Introduction: Dentinogenesis imperfecta (DI) has been defined as a hereditary alteration of autosomal dominant character, which originates during the stage of histodifferentiation in dental development, is a type of dysplasia of dentinal tissue that affects the dentine structure of one or both dentitions. The complications of ID have a strong impact on the quality of life of patients since the functional, aesthetic and phonetic part are usually affected and represent an important challenge for the trafficker. Early diagnosis and adequate treatment are necessary to achieve better functional and aesthetic results, minimize nutritional deficiencies and psychosocial disorders, thus improving the quality of life of the person. Objective: To determine the type of dentinogenesis, the family relationship, and the clinical characteristics of each patient. Methods: Two brothers coming from the city of Cuenca-Ecuador, ages 5 and 6 years old, come to the Odontology clinic of the Catholic University of Cuenca, respectively, for presenting multiple carious lesions. Generalized destruction of the coronary remnant and premature loss of teeth. After performing the clinical and radiographic diagnosis, family history, the diagnosis of dentinogenesis imperfecta type II was established. Conclusion: the timely and early diagnosis of dentinogenesisimperfecta is of great importance for an adequate treatment, because the ID, affected mainly by the primary dentition, is fundamental visits to the dentist, since this will be able to diagnose the pathology at an early stage. Avoid big damages.

Fatal neonatal nephrocutaneous syndrome in 18 Roma children with EGFR deficiency.

Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein with tyrosine-kinase signaling activity, involved in many cellular functions including cell growth and differentiation. Germ line loss-of-function mutations in EGFR lead to a severe neonatal skin disorder (Online Mendelian Inheritance in Man #131550). We report 18 premature Roma children from 16 families with birthweights ranging 440-1470 g and multisystem diseases due to the homozygous mutation c.1283G˃A (p.Gly428Asp) in EGFR. They presented with thin, translucent, fragile skin (14/15), skin desquamation (10/17), ichthyosis (9/17), recurrent skin infections and sepsis (9/12), nephromegaly (10/16) and congenital heart defects (7/17). Their prognosis was poor, and all died before the age of 6 months except one 13-year-old boy with a severe skin disorder, dentinogenesis imperfecta, Fanconi-like syndrome and secondary hyperaldosteronism. Management of ion and water imbalances and extremely demanding skin care may improve the unfavorable outcome of such patients.