EDA Variants Are Responsible for Approximately 90% of Deciduous Tooth Agenesis.

Deciduous tooth agenesis is a severe craniofacial developmental defect because it affects masticatory function from infancy and may result in delayed growth and development. Here, we aimed to identify the crucial pathogenic genes and clinical features of patients with deciduous tooth agenesis. We recruited 84 patients with severe deciduous tooth agenesis. Whole-exome and Sanger sequencing were used to identify the causative variants. Phenotype-genotype correlation analysis was conducted. We identified 54 different variants in 8 genes in 84 patients, including EDA (73, 86.9%), PAX9 (2, 2.4%), LRP6 (2, 2.4%), MSX1 (2, 2.4%), BMP4 (1, 1.2%), WNT10A (1, 1.2%), PITX2 (1, 1.2%), and EDARADD (1, 1.2%). Variants in ectodysplasin A (EDA) accounted for 86.9% of patients with deciduous tooth agenesis. Patients with the EDA variants had an average of 15.4 missing deciduous teeth. Mandibular deciduous central incisors had the highest missing rate (100%), followed by maxillary deciduous lateral incisors (98.8%) and mandibular deciduous lateral incisors (97.7%). Our results indicated that EDA gene variants are major pathogenic factors for deciduous tooth agenesis, and EDA is specifically required for deciduous tooth development. The results provide guidance for clinical diagnosis and genetic counseling of deciduous tooth agenesis.

Pre-implant surgery complexity for achieving implant-supported prosthetic rehabilitation in oligodontia patients: a retrospective study.

INTRODUCTION: Oligodontia is a rare dental developmental pathology that requires prolonged, complex and multidisciplinary treatment. Although bone augmentation is frequently required during a complete implant treatment of oligodontia. Therefore, we evaluated the ability to predict pre-implant surgery complexity based on age, number of missing teeth, and number of implants required to achieve implant-supported prosthetic rehabilitation. MATERIAL AND METHODS: This retrospectively registered study included all patients who underwent surgical treatment for oligodontia in our Oral and Maxillofacial Surgery Department between January 2012 and May 2023. Demographic data, number and location of missing teeth, pre- and per-implant surgical procedures, and the number of planned implants were recorded. A quantitative variable called "complexity score of pre-implant surgery" was created. This 10-point score was calculated by adding one point for each preimplant surgical procedure registered. A simple linear regression was calculated to explain the number of targeted implants based on number of missing teeth. A multiple linear regression model was used to explain the complexity score of pre-implant surgery and age, number of missing teeth and number of targeted implants. RESULTS: 119 oligodontia patients were included in the study. The median number of tooth agenesis was 10. A total of 825 implants were placed, 14 (1.7%) of which failed. A significant regression equation was used (F(1,118) = 1098,338; p < 0.0001) to explain the number of targeted implants based on number of missing teeth, with a R2 of 0.903. A significant regression equation was found (F(3,116) = 107,229; p < 0.0001) to explain the complexity score of pre-implant surgery and age, number of missing teeth and number of targeted implants, with a R2 of 0.735. DISCUSSION: These results based on patient data indicate that age, number of missing teeth and number of targeted implants could reliably explain the complexity of pre-implant surgery.

A comparative retrospective study on the prevalence and therapeutic treatment of dental agenesis between healthy children and children with systemic disease or congenital malformation.

BACKGROUND: Dental agenesis (DA) in the permanent dentition is one of the most common dental anomalies, with a prevalence up to 2-10%. Therefore, the aim of this retrospective study was to investigate the prevalence and therapeutic treatment of DA in healthy children (HC) compared to children with systemic disease or congenital malformation (SD/CM). METHODS: Out of 3407 patients treated at the Department of Paediatric Dentistry of the Justus Liebig University Giessen (Germany) between January 2015 and December 2020, a total of 1067 patients (594 female, 473 male) aged between 4.5 and 18 years were included in this study due to DA. Besides the patients' general medical history and therapeutic treatments, panoramic radiographs were analysed. RESULTS: In contrast to the HC group with 9.7% DA, the SD/CM group showed a significantly higher prevalence of DA (19.8%; p < 0.05). The latter group was further classified into children with ectodermal dysplasia (4.4%), down syndrome (8.2%), cleft lip and palate (4.4%), intellectual disability/developmental delay (16.4%), and other genetic/organic diseases without intellectual disability (45.9%). Regarding therapeutic treatments, the HC group (59.5%) was significantly more often treated with an orthodontic gap opening compared to the SD/CM group (42.6%; p < 0.05), followed by orthodontic gap closing 36.5% in the HC group and 22.9% in the SD/CM group (p < 0.05), whereas no treatment was predominantly performed in the SD/CM group (37.7%) compared to the HC group (4%; p < 0.05). Furthermore, 50% in the SD/CM group required general anaesthesia for therapeutic treatment (vs. 8.1% in the HC group; p < 0.05). CONCLUSIONS: Children with SD/CM suffered more often from DA compared to HC that underlines multi- and interdisciplinary treatment of utmost importance. Furthermore, due to intellectual disability, common treatment methods can be complicated by insufficient compliance. This fact underlines the importance of an early attempt to establish the necessary cooperation enabling children with SD/CM to receive therapy.

Patterns of nonsyndromic tooth agenesis and sexual dimorphism.

BACKGROUND: Sex dimorphism has been implicated in oral health differences and the pathogenesis of oral diseases, such as tooth agenesis, periodontal disease, dental caries, and tooth loss. Tooth agenesis (TA) is one of the most common developmental anomalies in humans, and its prevalence and patterns are different across ethnic groups. The aim of this study was to investigate the phenotypes and sex-associated patterns of nonsyndromic tooth agenesis (TA) in Thai dental patients. METHODS: One thousand ninety panoramic radiographs were examined. One hundred and one subjects (37 males, 64 females, 15-20 years-old) with nonsyndromic TA were evaluated. Differences in TA prevalence between groups were analyzed using the chi-square or Fisher exact test. RESULTS: The TA prevalence, excluding third molars, was 9.3% and more frequently found in the mandible compared with the maxilla. The maxilla demonstrated a higher prevalence of first premolar agenesis than the mandible (P = 0.012), while the mandible had a higher prevalence of second premolar agenesis than the maxilla (P = 0.031). There were significantly more males missing one tooth than females, however, there were more females missing two or more teeth than males (P = 0.042). A missing maxillary left lateral incisor was significantly more frequent in males (P = 0.019), while a missing mandibular right lateral incisor was more frequent in females (P = 0.025). In females, the pattern of two mandibular lateral incisors agenesis was the most common and significantly present in females more than males (P = 0.015). In contrast, the pattern of one mandibular left lateral incisor agenesis was only observed in males and significantly found in males more than females (P = 0.047). CONCLUSIONS: We demonstrate sex-associated differences in nonsyndromic tooth agenesis. The prevalence of single tooth agenesis was higher in males, while that of two or more teeth agenesis was higher in females. We found different patterns of lateral incisor agenesis between males and females.

Dental management of a pediatric patient with progressive familial intrahepatic cholestasis having dental anomalies: a case report and brief review of the literature.

BACKGROUND: Progressive familial intrahepatic cholestasis is a heterogeneous group of disorders, leading to intrahepatic cholestasis, with the possibility of chronic liver failure and biliary cirrhosis. Oligodontia is either the manifestation of a specific syndrome or is non-syndromic. To the best of our knowledge, this is the first case report of type 3 progressive familial intrahepatic cholestasis and concurrent oligodontia, craniosynostosis, dens in dente, taurodontism, and delayed permanent dentition in the medical and dental literature. CASE PRESENTATION: We present the dental and medical histories and comprehensive dental management of a girl with type 3 progressive familial intrahepatic cholestasis and several dental anomalies, who was referred to a dental clinic due to severe dental caries and pain. CONCLUSION: Our findings suggest that PFIC with manifestations as oligodontia, craniosynostosis, dens in dente, taurodontism, and delayed permanent dentition, might indicate an unknown syndrome; otherwise, the craniofacial anomalies are the manifestations of an independent disease coinciding with PFIC. Moreover, our case is a good example of the importance of timely medical and dental care in confining further health-related complications. The patient was able to ingest without any pain or discomfort after receiving proper dental management.

Consecutive tooth agenesis patterns in non-syndromic oligodontia.

Agenesis of two or more consecutive adjacent permanent teeth (consecutive tooth agenesis, CTA) is a serious manifestation of oligodontia requiring long-term, multi-disciplinary treatment. Therefore, the present study investigated the characteristics of the CTA pattern in orthodontic patients with non-syndromic oligodontia. Using panoramic radiographs, the number of agenetic permanent teeth excluding third molars in non-syndromic orthodontic patients was evaluated, and patients with six or more agenetic teeth (oligodontia group, n = 97) and with one to five agenetic teeth (hypodontia group, n = 107) were selected. The numbers of CTA including third molars in each quadrant and in each patient were compared between the groups. Each quadrant with CTA of patients was categorized into one of the following four types: (I) involves anterior teeth only; (II) involves posterior teeth only; (IIIA) includes anterior and posterior teeth; and (IIIB) separate in the anterior and posterior teeth. CTA in at least one quadrant was found in 91.8 and 4.7% of patients in the oligodontia and hypodontia groups, respectively. The highest frequency CTA patterns included agenesis of the first and second premolars and of the second and third molars in the oligodontia and hypodontia groups, respectively. In the oligodontia group, type IIIA was significantly more frequent in the maxillary than in the mandibular quadrant. Most oligodontia patients who visit orthodontic clinics have CTA. A rare but severe CTA pattern that continues from the anterior to posterior segments is more frequent in the maxillary than in the mandibular quadrant.

Recording jaw relation of a pediatric patient with ectodermal dysplasia and complete anodontia using a digital mini arch tracer: A case report.

Children with ectodermal dysplasia and complete anodontia experience difficulties in oral rehabilitation because of the small arch size. A case of a 7-year-old boy, whose arch size (length and width) was 30-40% smaller than that of a male adult and who presented with difficulties in jaw relation recording using commercially available devices is described. A digital workflow involving a mini arch tracer was introduced. Primary impressions were made using three-dimensionally (3D) printed mini trays produced based on the patient's computed tomography images, and digital primary casts were obtained based on the scanned and reversed primary impressions. The final custom impression trays with mini tracing plates were designed based on the primary casts. In addition, the hand shank, retention plate, and retainers were placed on the designed custom trays and 3D-printed to produce an individual arch tracer system. In addition, two height-checking buckles were designed to help adjust the height of a tracing screw. Finally, the jaw relation of the patient was recorded and transferred, and a set of complete dentures were delivered, satisfying both the patient and his family.

Are developmentally missing teeth a predictive risk marker of malignant diseases in non-syndromic individuals? A systematic review.

BACKGROUND: Different genes and loci that are associated with non-syndromic developmental tooth agenesis (TA) have the same causation pathway in the development of tumours including breast cancer (BC), epithelial ovarian cancer (EOC), colorectal cancer (CRC) and lung cancer (LC). OBJECTIVES: To assess the link between TA and the development of cancer. SEARCH SOURCES: This registered review included a comprehensive search of electronic databases (Cochrane Central Register of Controlled Trials [CENTRAL], LILACS, Scopus, Web of Science and Medline via Ovid) until 1 April 2020, supplemented by manual, grey literature and reference lists search. There was no restriction in term of date of publication, gender, race or type of hypodontia. DATA SELECTION: The primary outcome was the relationship between TA and cancer. The secondary outcome was to identify the genetic correlation between TA and cancer. DATA EXTRACTION: Study selection, data extraction and risk of bias assessment were performed independently and induplicate by two reviewers, with disputes resolved by a third reviewer. RESULTS: Eight studies with a moderate-high risk of bias were included in the final review, with a total of 5821 participants. Due to the heterogeneity among the included studies, the data were presented narratively. Limited studies reported a high prevalence of EOC (19.2%-20%) and CRC (82%-100%) in individuals with TA (depending on the study) compared to those without TA (3% for EOC and 0% for CRC). While others reported a weak correlation between EOC and CRC and TA (P > 0.05). Weak evidence suggested a strong correlation between breast, cervical uterine and prostate cancers and TA (P < 0.05). CONCLUSIONS: Though low-quality evidence suggests a link between TA and cancer, it was not possible to verify that TA can hold a predictive value as a marker for cancers. Further research is needed to confirm the association. REGISTRATION: PROSPERO (CRD42020139751).

Dimensional Changes in Dental Arches after Complete Dentures Rehabilitation of a Patient with Hypohidrotic Ectodermal Dysplasia: A Case Report with 18-Year Follow-Up.

BACKGROUND: This case report presents the dimensional changes in dental arches in a patient with hypohidrotic ectodermal dysplasia (HED) after complete denture rehabilitation, with an 18-year follow-up period. CASE REPORT: The patient had complete anodontia and was successfully rehabilitated with conventional complete dentures at 3, 4, 5, 7, 9, 12, 16, and 21 years of age. Each successive denture was larger and contained more and larger teeth so as to accommodate for the increase in the size of the developing jaw. A series of diagnostic casts were used to measure the dimensional changes in the arch length and width of the alveolar ridge. Cast analysis revealed that there was an increase in arch length and width in both the maxilla and mandible over time. Cephalometric analysis of craniofacial development was performed at 21 years of age, and suggested protrusion of the maxilla and mandible. CONCLUSIONS: The absence of teeth due to HED did not affect the dimensional changes in dental arches after complete denture rehabilitation from childhood to adulthood. The prosthetic treatment improved the patient's social integration and enabled the development of normal dietary habits, speech, and facial esthetics, which in turn led to improved quality of life.

Distinct impacts of bi-allelic WNT10A mutations on the permanent and primary dentitions in odonto-onycho-dermal dysplasia.

Odonto-onycho-dermal dysplasia (OODD) is a rare autosomal recessive syndrome characterized by multiple ectodermal abnormalities. Mutations of the wingless-type MMTV integration site family member 10A (WNT10A) gene have been associated with OODD. To date, only 11 OODD-associated WNT10A mutations have been reported. In this report, we Characterized the clinical manifestations with focusing on dental phenotypes in four unrelated OODD patients. By Sanger sequencing, we identified five novel mutations in the WNT10A gene, including two homozygous nonsense mutations c.1176C>A (p.Cys392*) and c.742C>T (p.Arg248*), one homozygous frame-shift mutation c.898-899delAT (p.Ile300Profs*126), and a compound heterozygous mutation c.826T>A (p.Cys276Ser) and c.949delG (p.Ala317Hisfs*121). Our findings confirmed that bi-allelic mutations of WNT10A were responsible for OODD and greatly expanded the mutation spectrum of OODD. For the first time, we demonstrated that bi-allelic WNT10A mutations could lead to anodontia of permanent teeth, which enhanced the phenotypic spectrum of WNT10A mutations. Interestingly, we found that bi-allelic mutations in the WNT10A gene preferentially affect the permanent dentition rather the primary dentition, suggesting that the molecular mechanisms regulated by WNT10A in the development of permanent teeth and deciduous teeth might be different.

Esthetic Rehabilitation of Retained Primary Teeth-A Conservative Approach.

With the advancement in ceramic restorations bonded to tooth structure, the treatment has become a feasible and conservative option to restore teeth with alteration in shape when owing to high demand in esthetics, with or without minimum tooth preparation. This article describes a report of a 32-year-old woman who was dissatisfied with her smile. The patient reported that she still had deciduous teeth, and that the maxillary lateral incisors had been restored with direct resin composite to correct the teeth shape. After discussing the restorative possibilities, a decision was made to place all-ceramic crowns (lithium disilicate glass-ceramic) with minimal tooth preparation, which figures as a conservative full-coverage approach. An esthetic outcome resembling a natural-looking smile resulted in the patient's satisfaction. Bonding of all-ceramic crowns onto minimally prepared deciduous teeth figures as a conservative treatment in case of partial anodontia, which decreases the chance of root resorption induced by trauma and benefits from good adhesion to enamel.

Prevalence of Hypodontia and Supernumerary Teeth in Patients Attending Private Pediatric Dental Clinic in Lebanon.

Purpose: Because of the high rate of agenesis and supernumerary teeth in orthodontic patients and the lack of studies in Lebanon that document the prevalence of those anomalies, the aim of this study was to determine the prevalence of hypodontia and supernumerary teeth in patients attending a pediatric dental office and examine the associated factors. Study design: This was a cross-sectional design study. The patients were clinically examined followed by panoramic radiograph. Two calibrated investigators have examined the radiographic films and diagnosed the dental anomalies. Tooth agenesis and supernumerary teeth were the outcome variables of the study. Tooth agenesis was diagnosed when there were no sign of crown calcification and no evidence or history of loss attributable to orthodontic treatment, caries, periodontal problems and dental trauma. Tooth agenesis and supernumerary teeth were the outcome variables of the study. Chi-Square tests and Fisher Exact tests were performed to assess the association between outcome variables, gender and presence of medical problem. Results: 334 participants (mean age 7.31±2.17 years) were included in the study. The presence of dental anomalies was not reported as a reason for dental visits. The rate of tooth agenesis was 8.7% in the whole sample, 9.9% among boys and 7.6% among girls with no difference (p=0.442). The rate of tooth agenesis was elevated in participant with medical problems (14.5%) compared to those with no medical problem (7.0%) (p=0.041). The rate of supernumerary teeth was 0.6% among boys and 0% among girls (p=0.485). Conclusion: Oral anomalies could be detected relatively at early age. It can help in a long-term and effective treatment planning. Early diagnosis and appropriate follow-up with panoramic radiograph is extremely important to avoid maxillofacial deformity and other complications.

Prosthetic rehabilitation of patients with hypohidrotic ectodermal dysplasia: A systematic review.

Hypohidrotic ectodermal dysplasia (HED) comprises a large group of inherited disorders of ectodermal structures, characterised by hypo- or anhidrosis, hypotrichosis and hypo- or oligo- or anodontia. We aimed to systematically assess the spectrum of prosthodontic approaches with regard to the patients' age and to provide clinical implications for practicing dentists. An electronic and manual search was conducted in four databases (Medline, LIVIVO, Cochrane Library, Web of Science Core Collection). Publications of multiple study designs written in English or German without data restrictions, reporting on prosthodontic treatment of patients diagnosed with HED and afflicted with oligo- or anodontia, were included. In total, 75 articles on 146 patients were analysed according to the patients' age. In children aged 2-17 years, removable full or partial (over)dentures represented standard treatment. In the mandible, implant-supported removable dentures on two interforaminal implants presented an alternative, already in young childhood. In cases with more than six teeth per jaw, also fixed (resin) bridges were used, frequently after orthodontic treatment. In adults, fixed or removable reconstructions with the help of up to eight implants per jaw, usually placed after bone augmentation procedures, were standard. Ten case reports/series with long-term follow-up illustrated the need for consistent maintenance including denture renewals. Prosthodontic rehabilitation should start in early childhood and needs to be revised in accordance with the patients' growth. Treatment should be carried out by a multidisciplinary team addressing variable demands in different age groups.

Prosthetic treatment outcome in patients with severe hypodontia: a systematic review.

Severe hypodontia (≥6 missing teeth) is associated with aesthetic and functional problems. Its presentation is heterogenic, and a variety of treatment modalities are used resulting in different treatment outcomes. As there is currently no standard treatment approach for patients with severe hypodontia, the literature was systematically reviewed with the focus on treatment outcomes. Medline, Embase and The Cochrane Central Register of Controlled Trials were searched (last search 24 August 2015). This was completed with a manual search of the reference lists of the selected studies. To be included, studies had to describe dental treatment outcome measure(s) in patients with severe hypodontia; there were no language restrictions. The methodological quality was assessed using MINORS criteria. Twenty-one studies were eligible, but the diversity in type and quality did not allow for a meta-analysis; seventeen studies had a retrospective design; sixteen studies described the results of implant treatment. Treatment with (partial) dentures, orthodontics, fixed crowns or bridges was sparsely presented in the eligible studies. Implant survival, the most frequently reported treatment outcome, ranging from 35·7% to 98·7%, was influenced by 'location' and 'bone volume'. The results of implant treatment in severe hypodontia patients are promising, but due to its heterogenic presentation, its low prevalence and the poor quality of the studies, evidence-based decision-making in the treatment of severe hypodontia is not yet feasible, thus prompting further research.

New recessive truncating mutation in LTBP3 in a family with oligodontia, short stature, and mitral valve prolapse.

Latent TGFB-binding protein 3 (LTBP3) is known to increase bio-availability of TGFB. A homozygous mutation in this gene has previously been associated with oligodontia and short stature in a single family. We report on two sisters with homozygous truncating mutations in LTBP3. In addition to oligodontia and short stature, both sisters have mitral valve prolapse, suggesting a link between truncating LTBP3 mutations and mitral valve disease mediated through the TGFB pathway.

Eruptive path of maxillary canines in patients with lateral incisor agenesis: a longitudinal follow-up.

OBJECTIVES: To evaluate the eruptive angle, mesiodistal position and height of permanent maxillary canines in patients with agenesis of the permanent maxillary lateral incisor (AL) from the mixed to the permanent dentition. MATERIALS AND METHODS: The sample was composed of orthodontic records of subjects with and without AL. The agenesis group comprised 11 patients, 7 with bilateral and 4 with unilateral AL (8.6 ± 1.6 years, 4 males, 7 females). The control group comprised 9 patients (8.5 ± 1.0 years, 2 males, 7 females) without AL. Panoramic radiographs were analyzed at three timepoints: inter-transitional period (T1), second transitional period (10.1±0.9 years, T2) and permanent dentition (11.9±1.1 years, T3). The long axis angle of the permanent maxillary canine (α and ß), the mesiodistal distance (d) in relation to the central incisor, and the height (H) from the cusp tip of the canine to the occlusal plane were evaluated. Intergroup comparisons were performed with t-tests, Mann-Whitney, and Chi-square tests (P < 0.05). RESULTS: A mesial position of the canine cusp tip relative to the distal of the permanent maxillary central incisor was observed for the agenesis group at T1, T2 and T3. From T1 to T2, the agenesis group showed greater occlusal displacement of the canine tooth germ. CONCLUSIONS: In patients with AL, canine tooth germs showed more mesial displacement and erupted a mean of 4.5 mm closer to the maxillary central incisors. Eruption of maxillary canines tended to be accelerated during the late mixed dentition in patients with AL.

Personalized and Complex Esthetic Oral Rehabilitation in a Case of Non-Syndromic Oligodontia.

Dental agenesis is one of the most common developmental anomalies in humans and it is frequently associated with several other oral abnormalities. The present case describes non-familial agenesis of permanent teeth in a twenty-one-year-old boy with no apparent systemic abnormalities. The treatment included a personalized and interdisciplinary approach involving endodontics, orthodontics, implant-supported restorations and prosthetic treatments. The treatment plan was thoroughly elaborated using photographic analysis, study models, orthopantomogram, CBCT and cephalograms. Virtual smile design, diagnostic waxing and mock-ups previsualized the treatment objectives. The edentulous spaces were reconstructed by inserting dental implants and monolithic zirconia implant-supported restorations. The final results showed a highly esthetic and functional rehabilitation. Periodic check-ups have shown that the stability of the result is well maintained and that the implant-supported restorations are an optimal solution for patients with multiple anodontia.

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.

Christ-Siemens-Touraine Syndrome: A Report of a Rare Pediatric Case.

Anhidrotic ectodermal dysplasia (AED), or Christ-Siemens-Touraine syndrome, is an X-linked recessive dermatosis. Rare in incidence, it affects 1 in 100,000 births, mostly boys. Through this observation, we detail the clinical signs that led us to suspect the diagnosis, how this pathology was confirmed, and the therapeutic management we carried out. We present a case of a 10-month-old boy presenting with altered manifestations affecting almost all the ectodermal structures like skin, hair, nails, teeth, sebaceous glands, sweat glands, and tear glands. He also had complete anodontia and a dry mouth. A multidisciplinary treatment was given to the patient with the collaboration of various health professionals. Although Christ-Siemens-Touraine syndrome is a rare condition, it is vital to recognize it early to improve care and prognosis for these patients, while mitigating the psychological impact of the condition on both children and parents.

GAPO syndrome: a novel variant in ANTXR1 gene.

BACKGROUND: GAPO syndrome is a rare autosomal recessive disorder characterized by the acronym of growth retardation, alopecia, pseudo-anodontia and progressive optic atrophy. While the genetic alteration of the ANTXR1 gene has been known for its cause, the full range of its clinical and genetic manifestations is not well explored due to the syndrome's extreme rarity. MATERIALS/METHODS: We report two children born to a non-consanguineous parent in India with classical features of GAPO syndrome. The whole exome sequencing analysis (WES) was performed in both siblings, and the parent's genetic and clinical status was determined. The identified variation was characterized in silico using homology-based protein modelling. RESULTS: In WES analysis, a homozygous ANTXR1 gene indel variant c. 151_152 + 2delAAGT (p.Lys51fs) was identified in both siblings. The parents were identified as the carriers of the ANTXR1 variant. Additionally, they also displayed mild GAPO-related facial and glaucomatous features. In silico analysis and homology-based ANTXR1 protein structure illustrate a frameshift and the subsequent premature truncation of the protein. CONCLUSIONS: Our reports contribute to the comprehension of GAPO syndrome within the Indian context describing an ANTXR1 novel variant causing premature protein truncation. WES-based genetic testing can significantly aid in expertly diagnosing GAPO syndrome. In the present case scenario, a variable penetrance of ANTXR1 variation was acknowledged as the carrier parents also had a mild degree of GAPO-related features. Future reports that include parental clinical diagnosis can offer further insights in this context.