Three-dimensional evaluation of dental characteristics in patients with Cleidocranial dysplasia.

BACKGROUND: Cleidocranial dysplasia (CCD) is an autosomal dominant hereditary disorder. Besides skeletal abnormalities, CCD is often associated with dental complications, such as multiple supernumerary teeth and permanent teeth impaction or delayed eruption. METHODS: Supernumerary teeth of axial, sagittal and coronal CBCT view was characterized in detail and 3D image reconstruction was performed. Number and location of teeth, morphology of supernumerary teeth, positional relationship between supernumerary and adjacent permanent teeth, direction of supernumerary teeth in CCD patients were analyzed. RESULTS: The mean age of the 3 CCD patients in this study was 16.7 years. Among 36 supernumerary teeth, the majority of them were identified as apical side located and lingual side located. Normal orientation was the most common type in this study, followed by sagittal orientation, and horizontal orientation. Horizontal orientation teeth were all distributed in the mandible. Supernumerary teeth exhibited significantly shorter crown and dental-root lengths, as well as smaller crown mesiodistal and buccolingual diameters (P < 0.01). There was no difference in the number of supernumerary teeth between the maxilla and mandible, and the premolars region had the largest number of supernumerary teeth and the incisor region had the smallest number. CONCLUSIONS: This study compares number and location of teeth, morphology of supernumerary teeth, positional relationship between supernumerary and adjacent permanent teeth and direction of supernumerary teeth, this study also provides a reference for the comprehensive evaluation of CCD patients before surgery.

Restoration of a Maxillary Anterior Defect With a Rotational Path Removable Partial Denture: Clinical Report of a Patient With Cleidocranial Dysplasia.

Cleidocranial dysplasia (CCD) is an uncommon genetic condition that affects teeth and bones, potentially leading to delayed ossification, dental abnormalities, and craniofacial changes, which can be treated through a combination of orthodontic and prosthodontic therapies. This case report describes the diagnostic evaluation, laboratory procedures, and prosthodontic treatment for a patient with CCD who had two missing maxillary anterior teeth. Following occlusal device therapy and the achievement of occlusal equilibration, restorative treatment was performed, consisting of a maxillary central incisor survey crown, rest seat preparations, and a lateral rotational path removable partial denture (RPD). The article highlights the value of this type of RPD as an alternative restoration for the replacement of missing anterior teeth.

Suspected Endodontic Failure in a Patient with Cleidocranial Dysplasia: A Case Report.

A patient's medical history and related dental manifestations can significantly contribute to confounding signs and symptoms leading to a diagnostic challenge. An 18-year-old female patient presented with persistent radiographic radiolucency associated with the apex of a previously treated tooth (tooth 9); asymptomatic apical periodontitis and endodontic failure were suspected. This report presents how a patient's condition of cleidocranial dysplasia had a profound effect on her dental history, which included the presence of multiple supernumerary teeth. Extensive surgical intervention during the patient's childhood was required to remove the supernumerary teeth, which resulted in an endodontic misdiagnosis in her adult life. After clinical and radiographic examination, the patient was diagnosed with a periapical scar. Periapical fibrous scars have a prevalence of between 2.5% and 12% and are a rare healing process with fibrous tissue after surgical and nonsurgical interventions. This report describes the diagnosis and pathophysiology of fibrous scars, including their risk factors and long-term monitoring approaches.

RUNX2 Nonsense Mutation Associated with Cleidocranial Dysplasia with Unusual Dental Features.

Purpose: The purpose of this case report is to describe a RUNX2 nonsense mutation associated with cleidocranial dysplasia (CCD) with unusual dental features. The patient was a 12-year-old Brazilian girl who sought dental care due to over-retention of primary teeth and absence of erupted permanent teeth. Clinical and radiographic examinations revealed multiple impacted permanent teeth, a prominent cingulum of the permanent impacted maxillary incisors and enamel defects (hypoplasia and hypomineralization) in addition to skeletal abnormalities. No supernumerary teeth were present. The diagnostic hypothesis of CCD was raised and the patient was refer- red to the genetic medical service, where the diagnosis was cofirmed. After RUNX2 genetic screening, including polymerase chain reaction and sequencing of both DNA strands, a heterozygous nonsense mutation was identified in exon 2 (c.193 C>T [Q65X]). This article reports unusual dental features in a patient with CCD.

A Novel 90-kbp Deletion of RUNX2 Associated with Cleidocranial Dysplasia.

Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia caused by runt-related transcription factor 2 (RUNX2) mutations. In addition to the regular missense, small or large fragment deletions are the common mutation types of RUNX2. This study aimed to find the rules of deletions in RUNX2. The clinical information of one Chinese CCD family was collected. Genomic DNA was extracted for whole-exome sequencing (WES). Bioinformatics analyzed the pathogenicity of the variants. Polymerase chain reaction (PCR) and Sanger sequencing were carried out using specific primers. RT-PCR and Q-PCR were also used to detect the mRNA level of RUNX2. The CCD studies related with deletions in RUNX2 from 1999 to 2021 from HGMD and PubMed were collected and analyzed for the relationship between the phenotypes and the length of deleted fragments. The proband presented typical CCD features, including delayed closure of cranial sutures, clavicle dysplasia, abnormal teeth. WES, PCR with specific primers and Sanger sequencing revealed a novel heterozygous 90-kbp deletion in RUNX2 (NG_008020.2 g.103671~193943), which caused a substitution (p.Asn183Ile) and premature termination (p.Asp184*). In addition, the mRNA expression of RUNX2 was decreased by 75.5% in the proband. Herein, 31 types of deletions varying from 2 bp to 800 kbp or covering the whole gene of RUNX2 were compared and the significant phenotypic difference was not found among these deletions. The CCD phenotypes were related with the final effects of RUNX2 mutation instead of the length of deletion. WES has the defects in identifying large indels, and direct PCR with specific primers and Sanger sequencing could make up for the shortcoming.

Cleidocranial dysplasia and novel RUNX2 variants: dental, craniofacial, and osseous manifestations.

OBJECTIVES: Cleidocranial dysplasia (CCD) is a skeletal disorder affecting cranial sutures, teeth, and clavicles, and is associated with the RUNX2 mutations. Although numerous patients have been described, a direct genotype-phenotype correlation for RUNX2 has been difficult to establish. Further cases must be studied to understand the clinical and genetic spectra of CCD. To characterize detailed phenotypes and identify variants causing CCD in five unrelated patients and their family members. METHODOLOGY: Clinical and radiographic examinations were performed. Genetic variants were identified by exome and Sanger sequencing, data were analyzed by bioinformatics tools. RESULTS: Three cases were sporadic and two were familial. Exome sequencing successfully detected the heterozygous pathogenic RUNX2 variants in all affected individuals. Three were novel, comprising a frameshift c.739delA (p.(Ser247Valfs*)) in exon 6 (Patient-1), a nonsense c.901C>T (p.(Gln301*)) in exon 7 (Patient-2 and affected mother), and a nonsense c.1081C>T (p.(Gln361*)) in exon 8 (Patient-3). Two previously reported variants were missense: the c.673C>T (p.(Arg225Trp)) (Patient-4) and c.674G>A (p.(Arg225Gln)) (Patient-5) in exon 5 within the Runt homology domain. Patient-1, Patient-2, and Patient-4 with permanent dentition had thirty, nineteen, and twenty unerupted teeth, respectively; whereas Patient-3 and Patient-5, with deciduous dentition, had normally developed teeth. All patients exhibited typical CCD features, but the following uncommon/unreported phenotypes were observed: left fourth ray brachymetatarsia (Patient-1), normal clavicles (Patient-2 and affected mother), phalangeal malformations (Patient-3), and normal primary dentition (Patient-3, Patient-5). CONCLUSIONS: The study shows that exome sequencing is effective to detect mutation across ethnics. The two p.Arg225 variants confirm that the Runt homology domain is vital for RUNX2 function. Here, we report a new CCD feature, unilateral brachymetatarsia, and three novel truncating variants, expanding the phenotypic and genotypic spectra of RUNX2 , as well as show that the CCD patients can have normal deciduous teeth, but must be monitored for permanent teeth anomalies.

Hypophosphatasia and cleidocranial dysplasia-a case report and review of the literature: the role of the neurosurgeon.

Hypophosphatasia (HPT) and cleidocranial dysplasia (CCD) are rare genetic disorders characterized by both defective ossification and bone mineralization. Patients usually present with craniosynostosis and cranial defects which in many cases require surgical repair. There is only 1 reported case of combined HPT and CCD in the literature. Our reported case involves a 3.5-year-old girl with concomitant homozygous CCD and heterozygous HPT. The child had an extended cranial defect since birth which improved with the administration of Strensiq and was followed until preschool age. Bone defects were relatively minor on revaluation. Due to the limited final defect, we decided not to intervene. In HPT-CCD patients, bone defects are overestimated due to osteomalacia, and thus, management strategy should be less aggressive. They should undergo surgical repair with cranioplasty with the use of cement and/or titanium meshes in case of extended final defects.

Congenital Pseudarthrosis of the Tibia Associated With Cleidocranial Dysostosis: Case Report and Literature Review.

CASE: We describe a case of 2 individually rare diseases existing comorbidly in the form of congenital pseudarthrosis of the tibia (CPT) coincident with cleidocranial dysostosis and provide a review of the literature, including the sole preexisting documented coincidence. CONCLUSION: Understanding, treatment, and surgical protocol of CPT have changed considerably since this comorbidity was last reported. Updates include synostosis, periosteal grafting, the use of bone morphogenetic protein, and bisphosphonates. Our case varies from the previous in associated disorder and family history. The relationship between CBFA1 and RUNX2 genes may hold the key, but further study is needed.

Clinical and radiological characterization of novel FIG4-related combined system disease with neuropathy.

Variants in the FIG4 gene, which encodes a phosphatidylinositol-3,5-bisphosphatase lead to obstruction of endocytic trafficking, causing accumulation of enlarged vesicles in murine peripheral neurons and fibroblasts. Bi-allelic pathogenic variants in FIG4 are associated with neurological disorders including Charcot-Marie-Tooth disease type-4J (CMT4J) and Yunis-Varón syndrome (YVS). We present four probands from three unrelated families, all homozygous for a recurrent FIG4 missense variant c.506A>C p.(Tyr169Ser), with a novel phenotype involving features of both CMT4J and YVS. Three presented with infant-onset dystonia and one with hypotonia. All have depressed lower limb reflexes and distal muscle weakness, two have nerve conduction studies (NCS) consistent with severe sensorimotor demyelinating peripheral neuropathy and one had NCS showing patchy intermediate/mildly reduced motor conduction velocities. All have cognitive impairment and three have swallowing difficulties. MRI showed cerebellar atrophy and bilateral T2 hyperintense medullary swellings in all patients. These children represent a novel clinicoradiological phenotype and suggest that phenotypes associated with FIG4 missense variants do not neatly fall into previously described diagnoses but can present with variable features. Analysis of this gene should be considered in patients with central and peripheral neurological signs and medullary radiological changes, providing earlier diagnosis and informing reproductive choices.

Cleidocranial dysplasia syndrome with epilepsy: a case report.

BACKGROUND: Cleidocranial dysplasia is a rare autosomal dominant disorder resulting in skeletal and dental abnormalities due to the disturbance in ossification of the bones. The prevalence of CCD is one in a million of live births, and epileptic seizures are rarer in this disease. CASE PRESENTATION: Herein, we present a case of a 10-year-old girl, who not only suffered with cleidocranial dysplasia, but experienced frequent seizures. We initiated an anti-epileptic treatment for this patient with dose adjustments to her weight of levetiracetam (10 mg/kg, bid) for 3 months. The epileptic seizures were controlled, but the intelligence level and control of epilepsy need to be followed up for a longer duration. CONCLUSIONS: In clinical practice, if a patient has unusual facies, typical clavicle defect, skull bone enlargement, and unclosed anterior fontanelle, we should consider the possibility of cleidocranial dysplasia, genetic detection are helpful to make a confirmed diagnosis. In such cases, early diagnosis and treatment is important to correct deformities and improve the quality of life of patients.

Cleidocranial Dysplasia: Presentation of Clinical and Radiological Features of a Rare Syndromic Entity.

Cleidocranial dysplasia is a developmental anomaly of the skeleton and the teeth. This condition may be inherited and be transmitted as dominant characteristics in either gender, or may appear spontaneously. It presents with skeletal defects of several bones, such as partial or complete absence of clavicles, late closure of the fontanels, presence of open skull sutures and multiple wormian bones. The dental manifestations are mainly delayed exfoliation of primary teeth and delayed eruption of permanent teeth with multiple impacted supernumerary teeth. This case of a 20 year old girl is noteworthy to the dentist as it deals with clinical and radiological features (a high number of impacted and supernumerary teeth as well as brachycephaly, frontal bossing and hypermobility of shoulders) which may come handy in clinical practice.

Oral rehabilitation with implant-supported fixed dental prostheses of a patient with cleidocranial dysplasia.

This clinical report describes the oral rehabilitation with implant-supported fixed dental prostheses in the maxilla and mandible of a patient with cleidocranial dysplasia. Cone-beam computed tomography and a tilted implant protocol in the mandible helped to establish a conservative approach for bone preservation, prevent surgical complications, enable proper implant positioning to avoid anatomic structures, and support the fixed dental prostheses.

A limb-girdle myopathy phenotype of RUNX2 mutation in a patient with cleidocranial dysplasia: a case study and literature review.

BACKGROUND: Cleidocranial dysplasia (CCD) is a rare hereditary disorder that arises from heterozygous loss of function mutations in the runt-related transcription factor 2 (RUNX2) gene. As RUNX2 is mainly expressed in osteoblasts, CCD typically affects the skeletal and dental systems. Few studies have investigated RUNX2 mutation effects on non-skeletal systems. Here, we describe limb-girdle myopathy, an uncommon phenotype of CCD, in a patient with a heterozygous missense mutation (p.R225Q) in the RUNX2 gene. CASE PRESENTATION: A 58 year-old man presented with progressive back pain and six months of weakness in the proximal parts of all four limbs. Physical examinations showed that he was short in stature (height, 164.4 cm; weight, 79.1 kg) with a dysmorphic face, including hypertelorism, midface hypoplasia, and chin protrusion. At a young age, he had received orthodontic surgery, due to dental abnormalities. Neurological examinations revealed sloping shoulders, weakness, and atrophy in the proximal areas of the arms, shoulder girdle muscles, and legs. The deep tendon reflex and sensory system were normal. Radiological examinations revealed mild scoliosis, shortened clavicles, and a depressed skull bone, which were consistent with a clinical diagnosis of CCD. Electromyography (EMG) studies showed myogenic polyphasic waves in the deltoid, biceps brachii, and rectus femoris muscles. Instead, the EMG findings were normal in the first dorsal interosseous, tibialis anterior and facial muscles. The EMG findings were compatible with a limb-girdle pattern with facial sparing. The patient's family history showed his father and eldest daughter with similar dysmorphic faces, skeletal disorders and proximal upper extremity weakness. We sequenced the RUNX2 gene and discovered a heterozygous missense mutation (c.G674A, p.R225Q), which altered the C-terminal end of the RUNX2 protein. This mutation was predicted to inactivate the protein and might affect its interactions with other proteins. This mutation co-segregated with the disease phenotypes in the family. CONCLUSIONS: We described limb-girdle myopathy in a patient with CCD that carried a heterozygous RUNX2 missense mutation. This uncommon phenotype expanded the phenotypic spectrum of the RUNX2 p.R225Q mutation. The role of RUNX2 in myogenic development merits future studies. Our findings remind clinicians that myopathic patients with myopathies combined with facial dysmorphism and shortened clavicles should consider the diagnosis of CCD.

Early dental treatments for patients with cleidocranial dysplasia.

OBJECTIVE: To explore the early dental interventional strategies for adolescent patients and a child patient with cleidocranial dysplasia (CCD). METHODS: Surgical exposure using the apically repositioned flap technique combined with orthodontic traction was used in the adolescent patients whose ideal treatment time for initiating treatment was missed. For the child patient whose ideal treatment time for initiating treatment was not missed, the simple surgical exposure method was carried out in order to promote the eruption of the impacted incisors. RESULTS: All the impacted maxillary incisors of the three CCD patients were successfully positioned into a proper alignment either through the two stages of crown exposure and the elastic traction or simple surgical exposure. CONCLUSION: Crown exposure surgery combined with light force orthodontic traction provides an effective approach to treat the typical dental abnormalities of adolescent CCD patients. Simple surgical exposure was also an effective way for a child CCD patient for whom the most ideal time for initiation of treatment was not missed.

Fabrication of lithium silicate ceramic veneers with a CAD/CAM approach: a clinical report of cleidocranial dysplasia.

The fabrication of minimally invasive ceramic veneers remains a challenge for dental restorations involving computer-aided design and computer-aided manufacturing (CAD/CAM). The application of an appropriate CAD/CAM protocol and correlation mode not only simplifies the fabrication of ceramic veneers but also improves the resulting esthetics. Ceramic veneers can restore tooth abnormalities caused by disorders such as cleidocranial dysplasia, enamel hypoplasia, or supernumerary teeth. This report illustrates the fabrication of dental veneers with a new lithium silicate ceramic and the CAD/CAM technique in a patient with cleidocranial dysplasia.

Cleidocranial dysplasia with bilateral posterior glenohumeral dislocation: a case-report.

A 31-year-old man experienced bilateral posterior glenohumeral dislocation during seizures. He had cleidocranial dysplasia with complete absence of both clavicles. Cleidocranial dysplasia is a rare inherited disease also known as Marie-Sainton syndrome and responsible for dental abnormalities well-known to stomatologists and dentists. Other manifestations include defective development of the skull bones and hypoplastic or aplastic clavicles. We found no previous reports of bilateral posterior glenohumeral dislocation in patients with cleidocranial dysplasia. The objective of this work was to look for an association between clavicular aplasia and posterior glenohumeral dislocation.

Multiple, supernumerary retained teeth in the course of cleido-cranial dysplasia. A case report.

Cleido-cranial dysplasia, often referred to as Scheuthauer-Marie-Sainton syndrome, is an autosomal dominant disorder of the musculo-skeletal system. Patients with cleido-cranial dysplasia are characterized by short stature, frequent varus or valgus hip, kyphoscoliosis, underdevelopment of the scapulas and the sternum, incorrect number of ribs. The most characteristic feature is unilateral or bilateral, partial or total underdevelopment of clavicles. Mental development is not affected in this syndrome. Malocclusion, occlusal irregularities, multiple supernumerary teeth, impacted teeth, and persistent milk teeth are found in the stomatognathic system. Teeth often have abnormal anatomy. Gothic palate, cleft hard and soft palate are diagnosed. The aim of this paper is to present a case of a 12-year-old boy diagnosed with irregularities in the masticatory system involving an additional number of retained teeth. The boy was referred by an orthodontist for surgical and orthodontic team therapy. The case presented confirms the observations of other authors that only the multi-specialty collaboration of a pediatrician, a geneticist, an orthopedist, an orthodontist, a maxillofacial surgeon, an implant prosthetic surgeon and a physiotherapist can provide proper diagnosis and treatment.