Investigation of the fungiform papillae number in children with tooth number anomalies.

OBJECTIVE: This cross-sectional study investigated the association between fungiform papillae (FP) numbers and tooth number anomalies in children, considering variables related to hypodontia and hyperdontia. The aim was to explore this association while adjusting for age and sex differences. MATERIALS AND METHODS: A total of 144 children (aged 8-10) were categorized into hypodontia (n = 48), hyperdontia (n = 48), and control groups (n = 48). Clinical and radiographic diagnoses were used to classify tooth number anomalies. Hypodontia was categorized by number and location, while hyperdontia was categorized by number, shape, and location. FP were assessed using the Denver Papillae Protocol. Data analyses were performed using NCSS software, with p < 0.05 considered statistically significant. RESULTS: The hypodontia group (22.5 ± 8.4) exhibited significantly lower FP than the control group (30.4 ± 9.2) and the hyperdontia group (27.9 ± 7.8) (p < 0.0005, p = 0.003, respectively). No significant difference existed between the hyperdontia and control groups. FP numbers in hypodontia subgroups showed no significant differences based on teeth agenesis numbers or locations. Similarly, hyperdontia subgroup analyses revealed no significant differences in FP numbers based on supernumerary teeth shapes (supplemental, conical, tuberculoid, paramolar) or the numbers of supernumerary teeth. CONCLUSIONS: The lower FP numbers in children with hypodontia suggested an association between teeth and FP number. However, the non-significant difference in FP numbers with hyperdontia underscored the complexity of tooth development, warranting further investigations. CLINICAL RELEVANCE: Children with hypodontia may exhibit distinct FP numbers compared to those without tooth number anomalies.

ANTXR1 deficiency promotes fibroblast senescence: implications for GAPO syndrome as a progeroid disorder.

ANTXR1 is one of two cell surface receptors mediating the uptake of the anthrax toxin into cells. Despite substantial research on its role in anthrax poisoning and a proposed function as a collagen receptor, ANTXR1's physiological functions remain largely undefined. Pathogenic variants in ANTXR1 lead to the rare GAPO syndrome, named for its four primary features: Growth retardation, Alopecia, Pseudoanodontia, and Optic atrophy. The disease is also associated with a complex range of other phenotypes impacting the cardiovascular, skeletal, pulmonary and nervous systems. Aberrant accumulation of extracellular matrix components and fibrosis are considered to be crucial components in the pathogenesis of GAPO syndrome, contributing to the shortened life expectancy of affected individuals. Nonetheless, the specific mechanisms connecting ANTXR1 deficiency to the clinical manifestations of GAPO syndrome are largely unexplored. In this study, we present evidence that ANTXR1 deficiency initiates a senescent phenotype in human fibroblasts, correlating with defects in nuclear architecture and actin dynamics. We provide novel insights into ANTXR1's physiological functions and propose GAPO syndrome to be reconsidered as a progeroid disorder highlighting an unexpected role for an integrin-like extracellular matrix receptor in human aging.

Evaluation of the aesthetics and clinical findings in patients with missing maxillary lateral incisors treated with a 10-year interval.

INTRODUCTION: The most common treatment approaches for patients missing maxillary lateral incisors are implant replacement (IT) and orthodontic space closure (SC). Treatment techniques change and improve over time, and it is of interest to know if improvements differ between the methods. AIM: To compare the aesthetic outcome and other clinical findings in patients with one or two missing maxillary lateral incisors who were treated with a 10-year difference in time, with either orthodontic space closure or implant replacement. MATERIAL AND METHODS: A total of 88 patients were included in the study. Forty-four patients treated between 2011 and 2018 were included as the latter cohort (LC). The LC was compared to the early cohort (EC; n = 44), treated between 2001 and 2008. A total of 132 teeth was analysed: 62 teeth in the EC (28 teeth in IT cases and 34 teeth in SC cases) and 70 teeth in the LC (34 teeth in IT cases and 36 teeth in SC cases). Long-term clinical and aesthetic outcomes were evaluated. RESULTS: An improvement over time was found in crown length, BoP, papilla, the inclination of incisors, and overall appearance in IT cases and in crown colour and overbite in SC cases. A deterioration over time was found in crown length and BoP among the SC cases. CONCLUSION: Among the IT cases, an improvement in outcomes was noted over time. When comparing SC cases the colour of the crown and overbite had improved, while crown length and BoP had deteriorated over time.

A 10-year-old boy with class II oligodontia treated with buccal fixed appliances and agenesis space closure of the four second premolars: Case report No. 230075 - Titularisation Collège Européen Orthodontie (CEO), European College of Orthodontics.

The patient presented in this case report is a 10-year-old boy with hyperdivergent skeletal Class II associated with familial genetic agenesis of the second premolars. The treatment plan chosen was to close the spaces of agenesis using a bimaxillary appliance fixed buccally. The advantages and disadvantages of this treatment option were discussed. The result was stable and made it possible to avoid an implant-prosthetic solution, which would undoubtedly have been more restrictive over time.

Identification of a novel de novo mutation in SOX4 for syndromic tooth agenesis.

OBJECTIVES: Coffin-Siris Syndrome (CSS) is a congenital disorder characterized by delayed growth, dysmorphic facial features, hypoplastic nails and phalanges of the fifth digit, and dental abnormalities. Tooth agenesis has been reported in CSS patients, but the mechanisms regulating this syndromic tooth agenesis remain largely unknown. This study aims to identify the pathogenic mutation of CSS presenting tooth genesis and explore potential regulatory mechanisms. MATERIALS AND METHODS: We utilized whole-exome sequencing to identify variants in a CSS patient, followed by Sanger validation. In silico analysis including conservation analysis, pathogenicity predictions, and 3D structural assessments were carried out. Additionally, single-cell RNA sequencing and fluorescence in situ hybridization (FISH) were applied to explore the spatio-temporal expression of Sox4 expression during murine tooth development. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to examine the functional role of SOX4. RESULTS: A novel de novo SOX4 missense mutation (c.1255C > G, p.Leu419Val) was identified in a Chinese CSS patient exhibiting tooth agenesis. Single-cell RNA sequencing and FISH further verified high expression of Sox4 during murine tooth development, and WGCNA confirmed its central role in tooth development pathways. Enriched functions included cell-substrate junctions, focal adhesion, and RNA splicing. CONCLUSIONS: Our findings link a novel SOX4 mutation to syndromic tooth agenesis in CSS. This is the first report of SOX4 missense mutation causing syndromic tooth agenesis. CLINICAL RELEVANCE: This study not only enhances our understanding of the pathogenic mutation for syndromic tooth agenesis but also provides genetic diagnosis and potential therapeutic insights for syndromic tooth agenesis.

"Examining the link between tooth agenesis and papillary thyroid cancer: is there a risk factor?" Observational study.

BACKGROUND: Mutations in one or multiple genes can lead to hypodontia and its characteristic features. Numerous studies have shown a strong genetic influence on the occurrence of hypodontia, and identified several genes, including AXIN2, EDA, FGF3, FGFR2, FGFR10, WNT10A, MSX1, and PAX9, that are directly associated with dental agenesis and carcinogenesis. The objective of this study was to investigate the occurrence and pattern of tooth agenesis, microdontia, and palatally displaced canine (PDC) in women diagnosed with papillary thyroid cancer (PTC), compared to a control group of women without any malignancy or thyroid disease. MATERIALS AND METHODS: This case-control study was carried at the Department of Orthodontics, School of Dental Medicine University of Zagreb, and Department of Oncology and Nuclear Medicine Sestre Milosrdnice University Hospital Centre. The study involved a clinical examination and evaluation of dental status, panoramic X-ray analysis, and assessment of medical and family history of 116 female patients aged 20-40 with PTC, as well as 424 females in the control group who were of similar age. RESULTS: The prevalence of hypodontia, microdontia, and PDC was statistically higher in women with PTC than in the control group. The prevalence rate of hypodontia was 11.3% in the experimental group and 3.5% in the control group. The experimental group showed a higher occurrence of missing upper lateral incisors, lower left central incisors, and all the third molars (except the upper left) compared to the control group. Women with PTC showed the prevalence of PDC significantly higher than the control group (3.5%, 0.7%, p = 0.002). The probability of hypodontia as a clinical finding increases 2.6 times, and microdontia occurs 7.7 times more frequently in women with PTC. CONCLUSION: Our study suggests a possible link between odontogenesis and PTC. The absence of permanent teeth may increase the likelihood of PTC in women. Leveraging the age-7 orthopantomogram to identify women at high risk for PTC within a critical early detection window could significantly improve oral health outcomes and PTC prognosis through proactive interventions.

Agenesis of the permanent teeth in sub-Saharan Africans: Prevalence, patterns, interpretations.

OBJECTIVE: Dental agenesis data in modern and premodern sub-Saharan Africans are presented by region, West, Central, East, and South, and by sex. Beyond characterizing the anomaly, comparisons are made with other populations and future work is encouraged. The findings should be of use to dental clinicians and anthropologists. METHODS: Agenesis of the UI2, LI1, UP2, LP2, UM3, and LM3 was recorded in 52 discrete samples of mainly skeletal dentitions (n = 2162) from across the subcontinent. After dividing into temporal categories, regional pooling was effected for adequate sample sizes across the vast geographic area. Only adults were included to record M3 status. Analyses included 95% confidence intervals and chi-square comparisons by region and sex. RESULTS: Of 1668 modern individuals 2.3% have UI2-LP2 agenesis (CI 1.6-3.1%). Regional and sex differences are non-significant, though females are most affected. For M3s it is 7.0% (5.7-8.4%), with the Central region sample differing significantly from the East and South. Females again have greater prevalence, with the difference in the West significant. UI2-LP2 agenesis affects 0.6% of 494 premodern individuals (0.1-1.8%), while M3 agenesis is 8.5% (6.1-11.5%). None of these differences are significant. CONCLUSIONS: Rates are toward the low end of global ranges, including 0.0-12.6% for UI2-LP2 from case reports, and 5.3-56.0% for M3 agenesis. With exceptions, generally insignificant inter-region differences imply that rates reasonably represent sub-Saharan peoples overall. Results will be of interest to anthropologists, but those related to risk factors, patterning, and prevalence may assist clinicians in tailoring treatment, while informing patients how this anomaly differs by population ancestry.

Difficulties experienced by dentists and orthodontists regarding ethical issues when announcing the diagnosis of a rare oral disease: a qualitative study in Marseille, France.

PURPOSE: It is traditionally considered that breaking bad news to patients does not represent a cause for concern for dental professionals. However, there are situations where they will be confronted with this task, as in the case of rare dental diseases. Little information is available regarding the feelings of healthcare professionals on this subject. There are no qualitative studies that explore how a diagnosis of oligodontia is announced to patients by dentists and orthodontists. The aim of our study is to explore the difficulties and ethical issues experienced by dental health professionals when they have to announce a diagnosis of oligodontia to a patient and their family. METHODS: This study relied on a qualitative research method using focus groups of dentists and orthodontists and a thematic analysis procedure. RESULTS: The difficulties experienced could be summarised within five topics: organisational difficulties, difficulties with the management of dental treatment and with the administrative management associated with this anomaly, difficulties with the content of the announcement, and relational difficulties. These could be grouped in two categories: practical difficulties and ethical difficulties. CONCLUSION: This survey allowed us to understand the difficulties encountered by dentists and orthodontists when announcing oligodontia. The participants felt uncomfortable with this task and were under stress. They reported difficulties in delivering the medical information and in adapting to the message. It is essential that dental professionals develop skills in medical communication.

Occlusal characteristics in modern humans with tooth agenesis.

Non-syndromic permanent tooth agenesis affects a significant proportion of the population, especially if third molars are considered. Although tooth agenesis has been linked to a smaller craniofacial size, reduced facial convexity and a shorter skeletal face, the occlusal characteristics of individuals with tooth agenesis remain largely unexplored. Therefore, this study investigated potential associations between tooth agenesis and metric occlusal traits in 806 individuals (491 with 4.1 missing teeth per subject, including third molars, and 315 without any tooth agenesis). Dentoskeletal morphology was defined through anatomical landmarks on pre-treatment cephalometric radiographs. Multivariate regression models, adjusted for sex and age, showed that tooth agenesis was significantly associated with a reduced overjet, an increased interincisal angle, and shorter upper and lower dental arch lengths, but not with overbite. Moreover, apart from reduced tooth length and dentoalveolar effects, as the number of missing teeth increased the upper front teeth were progressively retruded according to the craniofacial complex and to the face. Thus, tooth agenesis has a substantial influence on dental and occlusal characteristics, as well as on the sagittal position and inclination of anterior teeth. These findings emphasize the necessity for personalized, multidisciplinary approaches in individuals with multiple agenesis to successfully meet treatment goals.

Clinical analysis of nonsyndromic oligodontia phenotypes.

OBJECTIVES: To provide references, this study investigated the clinical characteristics of patients with nonsyndromic oligodontia. METHODS: The information of 178 patients with oligodontia was collected, including histories, oral examinations, and panoramic radiographs. Tooth agenesis characteristics were calculated and evaluated. All the data were statistically analyzed with SPSS 24.0 software. RESULTS: No significant difference in the number of missing teeth was found between sexes nor between the right and left sides, and congenitally missing teeth affected the maxillary arch (P<0.05). The highest prevalence of tooth agenesis was observed in the mandibular second premolars. In the maxillary arch, the most common pattern of tooth agenesis was agenesis of the bilateral first and second premolars. The agenesis of the bilateral second premolars was observed in the mandibular arch. The prevalence of a symmetric pattern between the right and left quadrants was significantly higher than that of matched patterns between the maxillary and mandibular antagonistic quadrants. Approximately 16.85% of patients with nonsyndromic oligodontia were affected by other tooth-related anomalies. CONCLUSIONS: The common patterns of tooth agenesis were successfully identified in patients with nonsyndromic oligodontia. Dentists need to provide multidisciplinary treatments for patients with nonsyndromic oligodontia because of variations in occluding and full-mouth tooth agenesis patterns.

Alveolar morphometry in young adults with and without agenesis of the upper lateral incisor: A retrospective study.

INTRODUCTION: We aimed to compare alveolar morphometry in young adults with agenesis of the upper lateral incisor versus the side without agenesis and versus matched controls. MATERIAL AND METHODS: In this observational retrospective study, cone beam computed tomography scans were obtained of 36 upper hemiarches from young adults aged 15 to 30 years. The hemiarches were distributed into three groups: group 1: 12 upper hemiarches presenting agenesis of the upper lateral incisor; group 2: 12 upper hemiarches from the opposite side without agenesis of the upper lateral incisor (control group 1); and group 3: 12 upper hemiarches without agenesis of the upper lateral incisor matched for age and sex with respect to the affected group (control group 2). A trained and calibrated investigator performed all the alveolar measurements at two different times, including sagittal, coronal and axial slices of each hemiarch. Paired Student's t-tests, Chi-square and repeated measures ANOVA with Bonferroni correction were used, (P<0.05). RESULTS: Apical mesial evaluation of group 1 (4.22±1.19mm) was significantly lower (P<0.001) than that of groups 2 (6.72±1.17mm) and 3 (7.58±1.67mm). Apical distal evaluation also showed differences (P<0.001) among the three groups, with the dimension being smaller in group 1 with agenesis (4.53±1.14mm), followed by group 2 without agenesis (6.23±1.55mm) and the healthy control group 3 (7.73±1.71mm). CONCLUSIONS: Lateral incisor agenesis significantly reduces the alveolar dimensions of the affected area. In cases of unilateral agenesis, the unaffected side also shows sequelae, with decreased dimensions compared to cases without agenesis. This condition should be taken into account when making therapeutic decisions regarding rehabilitation with implants or canine replacement.

Management options and long-term follow-ups for permanent double incisors: six to eleven-year case reports.

BACKGROUND: Double teeth are dental anomalies that can lead to aesthetic and orthodontic problems. CASE PRESENTATION: This report discusses two cases involving the multidisciplinary management of permanent maxillary left lateral incisors fused with a supernumerary tooth in two girls aged 9 and 10. Following intraoral and radiographic examinations, one was diagnosed with fusion, and the other was diagnosed with concrescence. The crown of the fused incisor was separated using a burs and extracted intraorally. The concrescent incisor was separated along its length using a laser and intentionally replanted extraorally. After a 6-year follow-up, no pathological signs were observed in the fused incisor. However, after an 11-year follow-up, external resorption was observed in the concrescent incisor. CONCLUSIONS: Both incisors remained asymptomatic throughout the observation period. This case report highlights two different and effective methods employed to preserve the natural function, form, and aesthetics of double incisors.

Prenatal onset GAPO syndrome with a novel ANTXR1 variant in an Indian child: Expansion of the phenotype & literature review.

GAPO syndrome is a rare genetic condition caused by bi-allelic variants in ANTXR1 gene & is an abbreviation for its core features - growth retardation, alopecia, pseudo-anodontia & optic atrophy. Certain additional features involving various other systems have been reported over the years & contribute to the expanding spectrum of this evolving phenotype. We report GAPO syndrome in a 3.75 year old Indian female child, who presented with some unique features such as sagittal craniosynostosis with scaphocephaly & bilateral choroid plexus cysts, alongside the core phenotype. We also report a novel frameshift variant in our patient & offer first evidence for the prenatal onset of some features.

Prevalence and Distribution of Dental Anomalies in Schoolchildren in Kuwait.

OBJECTIVE: Dental anomalies (DA) can affect paediatric patients' aesthetics, function, and psychological well-being. There is a lack of data about the prevalence of DA in children in Kuwait. This study aimed to investigate the prevalence and distribution of DA amongst schoolchildren aged 8 to 12 years. METHODS: A retrospective study was conducted using panoramic digital radiographs of children who attended a single dental center. All radiographs were evaluated by 2 calibrated and trained examiners. RESULTS: DA were present in 110 (20.1%) out of the 546 panoramic radiographs examined: 53.6% in females and 46.4% in males. The mean age of children with DA (9.83 ± 1.29) was similar to that of children with no anomalies (9.96 ± 1.46). The most prevalent anomaly was dental agenesis (9.3%), followed by taurodontism (6.6%) and ectopic eruption (EE, 2%). DA were more common in the maxilla (58.2%) compared to the mandible (41.8%, P = .042). Congenitally missing teeth were significantly more frequent in the mandible (56.9%) than in the maxilla (43.1%, P = .003). EE was significantly more common in the maxilla (90.9%) than in the mandible (9.1%, P = .024). Microdontia and root dilacerations were only present in males, whilst supernumerary teeth, transposition, and impacted teeth were noted in females only. CONCLUSIONS: The prevalence of DA amongst schoolchildren in Kuwait was considered to be relatively high. Certain DA were associated with gender. The significant prevalence of DA highlights the need for early diagnosis using panoramic radiographs, particularly during the ages of 9 and 10, in order to ensure effective patient management.

Repeated implants failure in young patient with idiopathic nephrotic syndrome: a case report with brief review of the literature.

BACKGROUND: Nephrotic syndrome is a chronic disorder characterized by heavy proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Idiopathic minimal-change disease is the most common form encountered in children. Corticosteroids are the cornerstone for the treatment of idiopathic nephrotic syndrome (INS), with different regimens depending on the response to therapy and frequency of relapses. This case report presents complications after implant treatment in patient with INS. CASE PRESENTATION: 20 years old female patient presented for implant consultation. Medical history includes INS since early childhood, and she is on different medications to control her condition, including long-term steroid use. Dental history revealed that implant treatment was unsuccessful after multiple attempts. She presented with an implant on the area of lower left first mandibular molar, that shows increased mobility and radiolucency on radiographic examination. A diagnosis of implant failure was made, the implant was removed, and the area was cleaned and sutured. The patient decided to replace her missing teeth with fixed partial denture and was referred for prosthodontist. The potential adverse effect of steroid use and the possible underlying mechanism that could affect bone metabolism and implants osseointegration are reviewed. CONCLUSION: Clinical practice guidelines are needed for the management of dental implants in chronic steroid users.

Compound heterozygous WNT10A missense variations exacerbated the tooth agenesis caused by hypohidrotic ectodermal dysplasia.

BACKGROUND: The aim of this study was to analyse the differences in the phenotypes of missing teeth between a pair of brothers with hypohidrotic ectodermal dysplasia (HED) and to investigate the underlying mechanism by comparing the mutated gene loci between the brothers with whole-exome sequencing. METHODS: The clinical data of the patients and their mother were collected, and genomic DNA was extracted from peripheral blood samples. By Whole-exome sequencing filtered for a minor allele frequency (MAF) ≤0.05 non-synonymous single-nucleotide variations and insertions/deletions variations in genes previously associated with tooth agenesis, and variations considered as potentially pathogenic were assessed by SIFT, Polyphen-2, CADD and ACMG. Sanger sequencing was performed to detect gene variations. The secondary and tertiary structures of the mutated proteins were predicted by PsiPred 4.0 and AlphaFold 2. RESULTS: Both brothers were clinically diagnosed with HED, but the younger brother had more teeth than the elder brother. An EDA variation (c.878 T > G) was identified in both brothers. Additionally, compound heterozygous variations of WNT10A (c.511C > T and c.637G > A) were identified in the elder brother. Digenic variations in EDA (c.878 T > G) and WNT10A (c.511C > T and c.637G > A) in the same patient have not been reported previously. The secondary structure of the variant WNT10A protein showed changes in the number and position of α-helices and ß-folds compared to the wild-type protein. The tertiary structure of the WNT10A variant and molecular simulation docking showed that the site and direction where WNT10A binds to FZD5 was changed. CONCLUSIONS: Compound heterozygous WNT10A missense variations may exacerbate the number of missing teeth in HED caused by EDA variation.

Patterns and sexual dimorphism of non-syndromic hypodontia among a French orthodontic population.

OBJECTIVES: This retrospective study aimed to estimate the prevalence of non-syndromic congenitally missing teeth (CMT) and to explore the frequency of CMT patterns in a French orthodontic population. In addition, the study sought to assess sex-based differences in CMT patterns. DESIGN: Panoramic radiographs of 4569 orthodontic patients between 9 and 21 years-old performed over a 16-year period (2006-2022) were examined to identify non-syndromic tooth agenesis, excluding third molars. A chi-square test or a Fisher exact test were used to determine the difference in the prevalence of tooth agenesis between sex and between arches. RESULTS: Tooth agenesis was observed in 7.3% of the sample (7.9% for females and 6.6% for males). Approximately 86% of the included subjects presented 1 or 2 missing teeth. Single tooth agenesis was significantly more frequent in females than males (p = 0.002, χ2). In total, 23 of the 67 different patterns of CMT observed, were present more than once. 75.5% of male patients and 79.5% of female patients presented one or both missing lateral incisors or second premolars, rarely affected at the same time. This study showed no sex difference in the patterns of tooth agenesis. LIMITATIONS: This study has limitations due to its retrospective nature and our findings apply solely to an orthodontic population from a white ethnic background. CONCLUSIONS: Clinicians should be aware of this particular incisor/premolar phenotype regardless of biological sex. Issues associated with congenitally missing teeth can be managed more effectively with early teenage diagnosis.

The current applications of nano and biomaterials in drug delivery of dental implant.

BACKGROUND AND AIM: Dental implantology has revolutionized oral rehabilitation, offering a sophisticated solution for restoring missing teeth. Despite advancements, issues like infection, inflammation, and osseointegration persist. Nano and biomaterials, with their unique properties, present promising opportunities for enhancing dental implant therapies by improving drug delivery systems. This review discussed the current applications of nano and biomaterials in drug delivery for dental implants. METHOD: A literature review examined recent studies and advancements in nano and biomaterials for drug delivery in dental implantology. Various materials, including nanoparticles, biocompatible polymers, and bioactive coatings, were reviewed for their efficacy in controlled drug release, antimicrobial properties, and promotion of osseointegration. RESULTS: Nano and biomaterials exhibit considerable potential in improving drug delivery for dental implants. Nanostructured drug carriers demonstrate enhanced therapeutic efficacy, sustained release profiles, and improved biocompatibility. Furthermore, bioactive coatings contribute to better osseointegration and reduced risks of infections. CONCLUSION: Integrating current nano and biomaterials in drug delivery for dental implants holds promise for advancing clinical outcomes. Enhanced drug delivery systems can mitigate complications associated with dental implant procedures, offering improved infection control, reduced inflammation, and optimized osseointegration.

Absent meibomian glands and cone dystrophy in ADULT syndrome: identification by whole exome sequencing of pathogenic variants in two causal genes TP63 and CNGB3.

BACKGROUND: Ectrodactyly is a rare congenital limb malformation characterized by a deep median cleft of the hand and/or foot due to the absence of central rays. It could be isolated or depicts a part of diverse syndromic forms. Heterozygous pathogenic variants in the TP63 gene are responsible for at least four rare syndromic human disorders associated with ectrodactyly. Among them, ADULT (Acro-Dermato-Ungual-Lacrimal-Tooth) syndrome is characterized by ectodermal dysplasia, excessive freckling, nail dysplasia, and lacrimal duct obstruction, in addition to ectrodactyly and/or syndactyly. Ophthalmic findings are very common in TP63-related disorders, consisting mainly of lacrimal duct hypoplasia. Absent meibomian glands have also been well documented in EEC3 (Ectrodactyly Ectodermal dysplasia Cleft lip/palate) syndrome but not in ADULT syndrome. METHODS: We report a case of syndromic ectrodactyly consistent with ADULT syndrome, with an additional ophthalmic manifestation of agenesis of meibomian glands. The proband, as well as her elder sister, presented with congenital cone dystrophy.The molecular investigation was performed in the proband using Whole Exome Sequencing. Family segregation of the identified variants was confirmed by Sanger sequencing. RESULTS: Two clinically relevant variants were found in the proband: the novel de novo heterozygous missense c.931A > G (p.Ser311Gly) in the TP63 gene classified as pathogenic, and the homozygous nonsense pathogenic c.1810C > T (p.Arg604Ter) in the CNGB3 gene. The same homozygous CNGB3 variation was also found in the sister, explaining the cone dystrophy in both cases. CONCLUSIONS: Whole Exome Sequencing allowed dual molecular diagnoses: de novo TP63-related syndromic ectrodactyly and familial CNGB3-related congenital cone dystrophy.