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Heliyon Jan 2024Brachyolmia is a heterogeneous group of developmental disorders characterized by a short trunk, short stature, scoliosis, and generalized platyspondyly without...
Brachyolmia is a heterogeneous group of developmental disorders characterized by a short trunk, short stature, scoliosis, and generalized platyspondyly without significant deformities in the long bones. DASS (Dental Abnormalities and Short Stature), caused by alterations in the gene, was previously considered as a subtype of brachyolmia. The present study investigated three unrelated consanguineous families (A, B, C) with Brachyolmia and DASS from Egypt and Pakistan. In our Egyptian patients, we also observed hearing impairment. Exome sequencing was performed to determine the genetic causes of the diverse clinical conditions in the patients. Exome sequencing identified a novel homozygous splice acceptor site variant (:c.3629-1G > T; p. ?) responsible for DASS phenotypes and a known homozygous missense variant (: c.590T > C; p.Ile197Thr) causing hearing impairment in the Egyptian patients. In addition, two previously reported homozygous frameshift variants (:c.132delG; p.Pro45Argfs*25) and (:c.2216delG; p.Gly739Alafs*7) were identified in Pakistani patients. This study emphasizes the vital role of in the axial skeleton and tooth morphogenesis and expands the mutational spectrum of . We are reporting variants in seven patients of three families, majorly causing brachyolmia with dental and cardiac anomalies. Skeletal assessment documented short webbed neck, broad chest, evidences of mild long bones involvement, short distal phalanges, pes planus and osteopenic bone texture as additional associated findings expanding the clinical phenotype of DASS. The current study reveals that the hearing impairment phenotype in Egyptian patients of family A has a separate transmission mechanism independent of .
PubMed: 38192829
DOI: 10.1016/j.heliyon.2023.e23688 -
Heliyon Jan 2024Amelogenesis imperfecta is a rare genetic disorder that interferes with normal enamel formation. Of the 4 main types of amelogenesis imperfecta, hypoplastic (type 1) is...
Amelogenesis imperfecta is a rare genetic disorder that interferes with normal enamel formation. Of the 4 main types of amelogenesis imperfecta, hypoplastic (type 1) is the most prevalent, characterized by a quantitative alteration in enamel. The pitting or reduced thickness of the enamel results in generalized hypersensitivity, increased susceptibility to caries and infection, attrition, and a loss in vertical dimension of occlusion. Prosthodontic management of these patients can be challenging not only functionally and restoratively, but also from an emotional and psychosocial standpoint. This clinical report describes the prosthodontic management and rehabilitation of two young adult siblings with hypoplastic (type 1) amelogenesis imperfecta.
PubMed: 38192821
DOI: 10.1016/j.heliyon.2023.e23939 -
Cureus Dec 2023Amelogenesis imperfecta (AI) is a rare genetic disorder affecting children and adults. Knowledge about AI is limited to clinical representation and radiographical... (Review)
Review
Amelogenesis imperfecta (AI) is a rare genetic disorder affecting children and adults. Knowledge about AI is limited to clinical representation and radiographical findings. Various treatments are provided to children with AI, yet no definitive treatment guideline has been suggested in the literature. This scoping review highlights the knowledge of the etiology and classification of AI and synthesizes these findings in a comprehensive review, focusing mainly on the various forms of AI in children and management with a restorative conservative approach. Five electronic databases, namely, PubMed, Google Scholar, Embase, Web of Science, and Scopus, were searched for the relevant articles. The search was performed in two phases: first for title and abstract, and second for full-text articles. The studies included in this scoping review were published from 2013 to August 2023. The data extraction was done on a customized sheet. A total of 33 studies were included in this review, of which 19 were reports and series, seven were observational, and seven were reviews. Most patients included in this review suffered from the hypoplastic type of AI (54%), followed by hypomatured (36%), and hypocalcified (10%). The treatment modalities explained were divided into the following three phases: temporary, transient, and permanent. Almost all included reports suggested the requirement for guidelines for treating AI among young children. This scoping review suggests the need for guidelines for treating AI in children. Moreover, pediatric dentists should prioritize early diagnosis and treatment and long-term follow-up for AI in children to effectively enhance the patient's psychological well-being and overall quality of life.
PubMed: 38179349
DOI: 10.7759/cureus.49968 -
Cureus Dec 2023Odontogenic anomalies encompass deviations in dental morphology, orientation, or spatial positioning within the mandibular structures. This study probed the frequency of...
BACKGROUND
Odontogenic anomalies encompass deviations in dental morphology, orientation, or spatial positioning within the mandibular structures. This study probed the frequency of such dental malformations among orthodontic patients receiving treatment in Riyadh City, Saudi Arabia. Furthermore, the study sought to discern variations in the manifestation of these dental anomalies related to gender and nationality.
MATERIALS AND METHODS
A retrospective analysis was conducted on 384 panoramic radiographs belonging to orthodontic patients (comprising 222 males and 162 females) who sought treatment at orthodontic clinics of a privately owned university hospital in Riyadh City between 2017 and 2019. The patient records were scrutinized for various dental abnormalities, including but not limited to dilacerated teeth, supernumerary teeth, congenital absence of teeth, impactions, hyperdontia, hypodontia, taurodontism, tooth rotation, and amelogenesis imperfecta. The Chi-square test was employed to assess the correlation between the prevalence of dental anomalies and variables such as gender and nationality. A p-value of less than 0.05 was deemed statistically significant for all tests.
RESULTS
Among the assessed sample size of orthodontic patients, dental impactions emerged as the most prevalent dental anomaly, affecting 246 patients (64.1%). This was followed by the occurrence of supernumerary teeth in 31 patients (8.1%), hyperdontia in 29 patients (7.6%), and congenital absence of teeth in 28 patients (7.3%). Other less frequently observed dental irregularities included dilacerated teeth in 23 patients (6%), amelogenesis imperfecta in 12 patients (3.1%), taurodontism in 12 patients (3.1%), and tooth rotations in five patients (1.3%). A statistically significant gender-based disparity was observed, with dental impactions being more prevalent among males (n=154; 69.4%) than females (n=92; 56.8%). Conversely, supernumerary teeth were more prevalent among females (n=24; 14.8%) than males (n=7; 3.2%). No significant variation in the prevalence of dental anomalies was discernible across different nationalities.
CONCLUSION
Impactions and the presence of supernumerary teeth were the predominant dental anomalies detected among the studied orthodontic patient population. The prevalence of dental anomalies exhibited discernible variations based on gender but not nationality. These disparities could potentially influence orthodontic outcomes, underscoring the necessity for meticulous examination and tailored orthodontic treatment planning.
PubMed: 38174162
DOI: 10.7759/cureus.49893 -
Scientific Reports Jan 2024Kohlschütter-Tönz syndrome (KTS) is a rare autosomal recessive disorder characterized by severe intellectual disability, early-onset epileptic seizures, and...
Kohlschütter-Tönz syndrome (KTS) is a rare autosomal recessive disorder characterized by severe intellectual disability, early-onset epileptic seizures, and amelogenesis imperfecta. Here, we present a novel Rogdi mutant mouse deleting exons 6-11- a mutation found in KTS patients disabling ROGDI function. This Rogdi mutant model recapitulates most KTS symptoms. Mutants displayed pentylenetetrazol-induced seizures, confirming epilepsy susceptibility. Spontaneous locomotion and circadian activity tests demonstrate Rogdi mutant hyperactivity mirroring patient spasticity. Object recognition impairment indicates memory deficits. Rogdi mutant enamel was markedly less mature. Scanning electron microscopy confirmed its hypomineralized/hypomature crystallization, as well as its low mineral content. Transcriptomic RNA sequencing of postnatal day 5 lower incisors showed downregulated enamel matrix proteins Enam, Amelx, and Ambn. Enamel crystallization appears highly pH-dependent, cycling between an acidic and neutral pH during enamel maturation. Rogdi teeth exhibit no signs of cyclic dental acidification. Additionally, expression changes in Wdr72, Slc9a3r2, and Atp6v0c were identified as potential contributors to these tooth acidification abnormalities. These proteins interact through the acidifying V-ATPase complex. Here, we present the Rogdi mutant as a novel model to partially decipher KTS pathophysiology. Rogdi mutant defects in acidification might explain the unusual combination of enamel and rare neurological disease symptoms.
Topics: Humans; Animals; Mice; Amelogenesis Imperfecta; Epilepsy; Dementia; Seizures; Mutation; Tooth Abnormalities; Membrane Proteins; Nuclear Proteins
PubMed: 38172607
DOI: 10.1038/s41598-023-50870-2 -
Cureus Nov 2023This clinical case report presents the prosthetic rehabilitation of a 23-year-old male patient with generalized discolored and worn-out teeth, which were of aesthetic...
This clinical case report presents the prosthetic rehabilitation of a 23-year-old male patient with generalized discolored and worn-out teeth, which were of aesthetic and functional concern. In collaboration with the Department of Oral Medicine and Radiology and Oral Pathology, this clinical condition was diagnosed as amelogenesis imperfecta (AGI). AGI is a genetic odontological disorder that is an epithelial derivative of the developed tooth bud with enamel malformation. AGI typically affects both deciduous and permanent teeth. Patients generally have aesthetic complaints and compromised chewing efficiency with loss of vertical dimension. Prosthetically rehabilitating an AGI patient is a multidisciplinary approach to regain aesthetics, phonetics, and mastication. This article describes the full mouth rehabilitation, following the Pankey Mann Schuyler philosophy, of the patient with AGI involving all teeth. Full mouth rehabilitation was planned to restore aesthetics, phonetics, and mastication in four phases. First was prosthetic rehabilitation of the mandibular anterior teeth, followed by the maxillary anterior, mandibular posterior, and, finally, maxillary posterior teeth.
PubMed: 38073947
DOI: 10.7759/cureus.48395 -
International Journal of Oral Science Dec 2023Ameloblasts are specialized cells derived from the dental epithelium that produce enamel, a hierarchically structured tissue comprised of highly elongated...
Ameloblasts are specialized cells derived from the dental epithelium that produce enamel, a hierarchically structured tissue comprised of highly elongated hydroxylapatite (OHAp) crystallites. The unique function of the epithelial cells synthesizing crystallites and assembling them in a mechanically robust structure is not fully elucidated yet, partly due to limitations with in vitro experimental models. Herein, we demonstrate the ability to generate mineralizing dental epithelial organoids (DEOs) from adult dental epithelial stem cells (aDESCs) isolated from mouse incisor tissues. DEOs expressed ameloblast markers, could be maintained for more than five months (11 passages) in vitro in media containing modulators of Wnt, Egf, Bmp, Fgf and Notch signaling pathways, and were amenable to cryostorage. When transplanted underneath murine kidney capsules, organoids produced OHAp crystallites similar in composition, size, and shape to mineralized dental tissues, including some enamel-like elongated crystals. DEOs are thus a powerful in vitro model to study mineralization process by dental epithelium, which can pave the way to understanding amelogenesis and developing regenerative therapy of enamel.
Topics: Mice; Animals; Durapatite; Dental Enamel; Ameloblasts; Amelogenesis; Stem Cells; Organoids
PubMed: 38062012
DOI: 10.1038/s41368-023-00257-w -
Journal of Dental Research Jan 2024Amelogenesis imperfecta (AI) comprises a group of rare, inherited disorders with abnormal enamel formation. Ameloblastin (AMBN), the second most abundant enamel matrix...
Amelogenesis imperfecta (AI) comprises a group of rare, inherited disorders with abnormal enamel formation. Ameloblastin (AMBN), the second most abundant enamel matrix protein (EMP), plays a critical role in amelogenesis. Pathogenic biallelic loss-of-function variants are known to cause recessive hypoplastic AI. A report of a family with dominant hypoplastic AI attributed to AMBN missense change p.Pro357Ser, together with data from animal models, suggests that the consequences of variants in human AI remain incompletely characterized. Here we describe 5 new pathogenic variants in 11 individuals with AI. These fall within 3 groups by phenotype. Group 1, consisting of 6 families biallelic for combinations of 4 different variants, have yellow hypoplastic AI with poor-quality enamel, consistent with previous reports. Group 2, with 2 families, appears monoallelic for a variant shared with group 1 and has hypomaturation AI of near-normal enamel volume with pitting. Group 3 includes 3 families, all monoallelic for a fifth variant, which are affected by white hypoplastic AI with a thin intact enamel layer. Three variants, c.209C>G; p.(Ser70*) (groups 1 and 2), c.295T>C; p.(Tyr99His) (group 1), and c.76G>A; p.(Ala26Thr) (group 3) were identified in multiple families. Long-read locus sequencing revealed these variants are on the same conserved haplotype, implying they originate from a common ancestor. Data presented therefore provide further support for possible dominant as well as recessive inheritance for -related AI and for multiple contrasting phenotypes. In conclusion, our findings suggest pathogenic variants have a more complex impact on human AI than previously reported.
Topics: Animals; Humans; Amelogenesis; Amelogenesis Imperfecta; Dental Enamel Proteins; Pedigree; Phenotype
PubMed: 38058155
DOI: 10.1177/00220345231203694 -
Orphanet Journal of Rare Diseases Nov 2023Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis is a rare, autosomal recessive, skeletal disorder first described in 2018. This syndrome... (Review)
Review
Identification of novel homozygous nonsense SLC10A7 variant causing short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis and surgical management of spine.
BACKGROUND
Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis is a rare, autosomal recessive, skeletal disorder first described in 2018. This syndrome starts with pre- and postnatal developmental delay, and gradually presents with variable facial dysmorphisms, a short stature, amelogenesis imperfecta, and progressive skeletal dysplasia affecting the limbs, joints, hands, feet, and spine.
CASE PRESENTATION
We identified a homozygous novel nonsense mutation in exon 1 of SLC10A7 (NM_001300842.2: c.100G > T / p.Gly34*) segregating with the typical disease phenotype in a Han Chinese family. We reviewed the 12-year surgical treatment history with seven interventions on spine.
CONCLUSION
To date, only 12 cases of the SLC10A7 mutation have been reported, mainly from consanguineous families. Our patient showed a relatively severe and broad clinical phenotype compared with previously reported cases. In this patient, annual check-ups and timely surgeries led to a good outcome.
Topics: Humans; Amelogenesis Imperfecta; Dwarfism; Homozygote; Mutation; Osteochondrodysplasias; Pedigree; Scoliosis
PubMed: 38037133
DOI: 10.1186/s13023-023-02975-0 -
Frontiers in Physiology 2023
PubMed: 38028793
DOI: 10.3389/fphys.2023.1323504