Genetic Variants in KCTD1 Are Associated with Isolated Dental Anomalies.

KCTD1 plays crucial roles in regulating both the SHH and WNT/ß-catenin signaling pathways, which are essential for tooth development. The objective of this study was to investigate if genetic variants in KCTD1 might also be associated with isolated dental anomalies. We clinically and radiographically investigated 362 patients affected with isolated dental anomalies. Whole exome sequencing identified two unrelated families with rare (p.Arg241Gln) or novel (p.Pro243Ser) variants in KCTD1. The variants segregated with the dental anomalies in all nine patients from the two families. Clinical findings of the patients included taurodontism, unseparated roots, long roots, tooth agenesis, a supernumerary tooth, torus palatinus, and torus mandibularis. The role of Kctd1 in root development is supported by our immunohistochemical study showing high expression of Kctd1 in Hertwig epithelial root sheath. The KCTD1 variants in our patients are the first variants found to be located in the C-terminal domain, which might disrupt protein-protein interactions and/or SUMOylation and subsequently result in aberrant WNT-SHH-BMP signaling and isolated dental anomalies. Functional studies on the p.Arg241Gln variant are consistent with an impact on ß-catenin levels and canonical WNT signaling. This is the first report of the association of KCTD1 variants and isolated dental anomalies.

Oral manifestations of Ehlers-Danlos syndromes.

Ehlers-Danlos syndromes (EDS) are a group of inherited connective tissue disorders. Patients with EDS exhibit distinct pathologies of the teeth and the oral cavity. Here, we summarize the current knowledge in the various EDS types, in particular regarding severe changes in oral health-related quality of life, the differential emergence of periodontitis, characteristic yet highly cumbersome dental manifestations, apparent anomalies of oral soft tissues, and relevant issues related to dental implantology. Resolution of remaining open questions will primarily rely on the standardization of diagnostic criteria. Clinical centers that specialize on this rare pathology need to apply congruent approaches for exact characterization of clinical features in conjunction with genetic validation that should be reached without exception in all patients and relevant family members.

Rare Variants in LRP4 Are Associated with Mesiodens, Root Maldevelopment, and Oral Exostoses in Humans.

BACKGROUND: Low density lipoprotein receptor-related protein 4 (LRP4; MIM 604270) modulates WNT/ß-catenin signaling, through its binding of WNT ligands, and to co-receptors LRP5/6, and WNT inhibitors DKK1, SOSTDC1, and SOST. LRP4 binds to SOSTDC1 and WNT proteins establishing a negative feedback loop between Wnt/ß-catenin, Bmp, and Shh signaling during the bud and cap stages of tooth development. Consistent with a critical role for this complex in developing teeth, mice lacking Lrp4 or Sostdc1 have multiple dental anomalies including supernumerary incisors and molars. However, there is limited evidence supporting variants in LRP4 in human dental pathologies. METHODS: We clinically, radiographically, and molecularly investigated 94 Thai patients with mesiodens. Lrp4 mutant mice were generated in order to study the effects of aberrant Lrp4 expression in mice. RESULTS: Whole exome and Sanger sequencing identified three extremely rare variants (c.4154A>G, p.Asn1385Ser; c.3940G>A, p.Gly1314Ser; and c.448G>A, p.Asp150Asn) in LRP4 in seven patients with mesiodens. Two patients had oral exostoses and two patients had root maldevelopments. Supernumerary incisors were observed in Lrp4 mutant mice. CONCLUSIONS: Our study implicates heterozygous genetic variants in LRP4 as contributing factors in the presentation of mesiodens, root maldevelopments, and oral exostoses, possibly as a result of altered WNT/ß-catenin-BMP-SHH signaling.

Mutations in LRP6 highlight the role of WNT signaling in oral exostoses and dental anomalies.

OBJECTIVE: The objective of this study was to investigate molecular etiologies of oral exostoses and dental anomalies in 14 patients from eight families. METHODS: Oral and radiographic examinations were performed on every patient. Whole exome and Sanger sequencing were performed on DNA of the patients, the unaffected parents and unaffected siblings. LRP6 mutant proteins were modeled and analyzed. RESULTS: Five mutations in LRP6, including four missense (p.Glu72Lys, p.Lys82Asn, Tyr418His, and p.Ile773Val) and one nonsense mutation (p.Arg32Ter), were identified. These mutations have not been reported to be associated with dental anomalies or oral exostoses. Oral features included a variety of oral exostoses (7 of the 14 patients), root defects (6 of the 14 patients), and tooth agenesis (5 of the 14 patients). Less common dental anomalies included microdontia, tooth fusion, odontomas, and mesiodens. Analysis of the protein models of the five LRP6 mutations shed light on their likely impact on LRP6 protein structure and function. CONCLUSION: Fourteen patients with five LRP6 mutations, including two recurrent mutations and three novel ones, are reported. Our study shows for the first time that mutations in LRP6 are associated with mesiodens, fusion of teeth, odontomas, microdontia, long roots, molars with unseparated roots, and taurodontism.

Morphological, histological, and chemical analysis of first permanent molars with molar incisor malformation.

PURPOSE: Molar incisor malformation (MIM) is a dental anomaly rendering first permanent molar pulps inflamed/necrotic at a young age. It often affects permanent incisors, primary second molars and less frequently other teeth. The purpose of this study was to investigate the anatomy and histology of MIM in seeking insight into its pathogenesis. METHODS: Five MIM first permanent molars were examined with micro-computed tomography (micro-CT) for 3D morphology, with scanning electron microscopy for microanatomy, with energy-dispersive X-ray spectrometer (EDS) for chemical composition and for histology with optical microscopy. Composition differences were statistically determined using one-way ANOVA. RESULTS: Micro-CT confirmed dentin abnormalities in the middle and cervical third of the crown in the form of the radiodense 'cervical mineralized diaphragm' (CMD). This was peripherally intertwined with enamel fjords and projections severely disrupting the integrity of pulp chamber and its continuity with root canals. EDS showed increased Ca in CMD compared to dentin. The histological examination revealed anomalous osteodentin-like hard tissue with denticles in the CMD. CONCLUSION: An interconnection of anomalous cervical enamel with crown CMD dentin preceded to the severe pulp chamber and root dysplasias in MIM molar teeth.

A new lumbar vertebral anomaly in Goldenhar syndrome: A case report.

Goldenhar syndrome has reported incidence ranging from 1:3500 to 1:20000 live births. It consists of abnormalities involving the first and the second branchial arches and its etiology is heterogenous. A newborn with this condition can have a normal life and intelligence, so it is important to correctly diagnose and manage the various conditions associated with Goldenhar syndrome to preserve patient quality of life. This case report describes a unique vertebral abnormality in a patient with Goldenhar syndrome, where a lumbar nerve root or vessel traverses an anomalous vertically oriented osseous foramen in a lumbar spine pedicle. If this anomaly goes unidentified, pedicle screw placement may pose a significant surgical risk to the traversing nerve or vessel.

Conjoint Nerve Root an Intraoperative Challenge in Minimally Invasive Tubular Discectomy.

Conjoint nerve root (CNR) is an embryological nerve root anomaly that mainly involves the lumbosacral region. The presence of CNR during tubular discectomy raises the chances of failure in spinal surgery and the risk of neural injuries. Tubular discectomy can be challenging in the presence of CNR owing to limited visualization. Here, we present a technical note on two cases of L5-S1 disc prolapse in the presence of conjoint S1 nerve root that was operated via a minimally invasive tubular approach. Any intraoperative suspicion of CNR while using the tubular approach should prompt the surgeon to perform a thorough tubular decompression prior to nerve root retraction. In patients with a large disc, disc should be approached via the axilla because the axillary area between the dura and the medial boarder of the root is very easy to approach in the presence of CNR. Safe performance of tubular discectomy is possible even in the presence of CNR in the lumbar spine.

Novel L5-S1 interbody fusion technique for root anomalies or abnormal root configurations of L5-S1 foramens.

PURPOSE: We show in this study that if a root anomaly does not permit access to the disc space in the usual way, the technique we define here can be used. If the patient has a root anomaly or an abnormal root configuration at this level, inevitably, an anterior approach is preferred. MATERIALS AND METHODS: The patient's previous skin incision was used; the L5-S1 space was reached laterally without entering the midline. The dura in the midline and the L5 and S1 roots on both sides were exposed. They were reached through the adjacent points of both S1 pedicles by going around the upper edge of the sacrum, allowing the disc space to be evacuated. An autologous bone graft was placed on both sides of the space. T10-S1 pedicle screws were placed. An L1 pedicle osteotomy was performed and joined using two rods. RESULTS: The patient's back and leg pain disappeared after the surgery. The plain X-rays showed that the sagittal balance was restored. In this case, it is impossible to see the disc space because the nerve root blocks its view. CONCLUSIONS: The classic approach in such cases is to perform a fusion by either a transperitoneal or retroperitoneal approach or by performing a posterior intertransverse fusion. However, it is very challenging to execute an anterior L5-S1 fusion on a patient with pelvic retroversion. When the spinopelvic junction is included in the fusion, one common problem observed is pseudarthrosis. The surgical technique defined in this article makes it possible to drill the bone tissue through the disc space and the upper surface of the sacrum, accessing the pedicle bone. Then, a discectomy is performed at the disc space, a bone graft is placed, and a posterior lumbar interbody fusion is performed.

Nerve root anomalies detected intra-operatively technical nuances towards achieving a successful surgical outcome: our experience of three case reports at a tertiary level centre.

OBJECTIVE: Analysis of three case reports of nerve root anomalies detected intra-operatively and its implications. DESIGN: Data collected during one year prospective non-randomised study using hospital records. SETTING: Single tertiary care centre. SUBJECTS: 3 patients in one year period.

Karyotype, Pedigree and cone-beam computerized tomography analysis of a case of nonsyndromic pandental anomalies.

This case report presented a karyotype and pedigree analysis of a case with unusual combination of dental anomalies: Generalized short roots, talon cusps, dens invagination, low alveolar bone heights, very prominent cusp of carabelli and protostylid on first permanent molars, taurodontism of second permanent molars, rotated, missing and impacted teeth. None of the anomalies alone are rare. However, until date, nonsyndromic pandental anomalies that are affecting entire dentition with detailed karyotype, pedigree and cone-beam computerized tomography analysis have not been reported. The occurrence of these anomalies is probably incidental as the conditions are etiologically unrelated.

Incisivo lateral superior con dos raíces y dos conductos: caso clínico / Upper lateral incisor with two roots and two canals: a clinical case

Las anomalías en la morfología del incisivo lateral superior son de muy baja frecuencia. Las anomalías de desarrollo radicular pueden presentarse como alteraciones tanto en el número de conductos, como en el número de raíces, así como en ambas regiones a la vez. En el presente trabajo, se reporta el caso de un paciente que se presenta a la consulta con malestar en el incisivo lateral superior izquierdo. En laradiografía preoperatoria se detectó la presencia de dos conductos y dos raíces, sin anomalía morfológica de su corona clínica, con requerimiento de tratamiento endodóntico. Concluimos que una correcta interpretación de las imágenes radiográficas preoperatorias es esencial, para poder detectar estas variantes y tomar las consideraciones necesarias para el adecuado tratamiento endodóntico

Abnormalities in the morphology of the maxillary lateral incisor are very low frequency. Root development abnormalities can occur as alterations in the number of ducts and the number of roots, as well as two regions at once. In this paper, we report the case of a patient presenting with discomfort in the upper left lateral incisor. In preoperative radiography, we detected the presence of two channels and two roots, without morphological abnormality in clinical crown, with endodontic treatment requirement. We conclude that a correct interpretation of preoperative radiographic imaging is essential in order to detect these variants and take the necessary considerations for proper endodontic treatment.

Conjoined Lumbosacral Nerve Roots without Disc Herniation: Case Report / 대한정형외과학회잡지

Anomalies of the lumbosacral nerve roots, in which conjoined nerve roots are most common, are occasionally accompanied by herniated nucleus pulposus. Most of these anomalies were incidental findings from operations, and recent advances in diagnostic imaging techniques have increased the number of cases of lumbosacral root anomalies reported. All these anomalies are congenital, unilateral and almost exclusively situated at the L5-S1 segment. Diagnostic techniques, such as myelography, CT and MRI detect conjoined nerve root. Conjoined nerve root may be confused with a dumbbell tumor or extruded free disc fragment on CT scans. Surrounded by high-signal intensity epidural fat, a conjoined nerve root is more clearly depicted on MR images than on CT scans. Although the size of disc herniation was small, the symptom was magnified by a relatively fixed conjoined root. At surgery, it is necessary for a larger surgical exposure by means of hemi-laminectomy because of the fixation of the nerve roots, and difficulty in retraction. Recently, we experienced two cases of conjoined nerve root and presented them with a review of the literature.