OBJECTIVE: To investigate the prevalence of tooth agenesis and associated dental anomalies in Latvian adolescent dental patients and compare it to other European countries.
METHODS: Cross-sectional study of 2692 11-to-14-year-old patients (39.9% males and 60.1% females) attending Riga Stradins University Institute of Stomatology with panoramic radiographs taken between August 2020 and September 2021. Patients with any genetic syndromes were excluded. Data on tooth agenesis (excluding third molars) and other dental anomalies were recorded.
RESULTS: The prevalence of tooth agenesis in Latvian adolescent dental patients was 9.3% with no statistically significant difference between genders (χ2 test, p = 0.472). The most commonly missing teeth were mandibular second premolars, followed by upper lateral incisors and upper second premolars. There was a statistically significant association with the presence of other dental anomalies in tooth agenesis patients (p < 0.001).
CONCLUSIONS: This study found that the prevalence of non-syndromic tooth agenesis in Latvian adolescent dental patients was 9.3% with no statistically significant differences between the genders. Patients with tooth agenesis have a statistically significant possibility of the presence of other dental anomalies (p < 0.001).

OBJECTIVE: To investigate the role of Keratinocyte Differentiation Factor 1 (KDF1) in ectodermal dysplasia (ED) and nonsyndromic tooth agenesis (NSTA) and perform a literature review.
METHODS: Genome sequencing was used to identify genetic variants in a Thai, NSTA proband and validated through Sanger sequencing. Pathogenicity was assessed using ACMG guidelines, MetaRNN and AlphaMissense. A comprehensive review of KDF1/NSTA cases informed genotype-phenotype analysis of the proband.
RESULTS: The proband revealed multiple missing teeth, caries and extensive periodontal disease. Deep phenotyping showed no signs of ED beyond tooth agenesis. The identified novel KDF1 variant, p.Ile243Leu, was classified as \'likely pathogenic\' by ACMG and predicted as \'detrimental\' by MetaRNN and AlphaMissense analyses. A total of 14 reviewed KDF1 cases revealed ED-associated variants (3 variants in 8 patients) clustering in the region of amino acids 251-275, within the DUF4656 domain, while NSTA-causing variants (4 variants in 6 patients) were typically found in amino- or carboxy-termini to this region. KDF1/NSTA cases exhibited an average of 15 missing teeth, with a higher prevalence in the mandible.
CONCLUSIONS: This study identifies a novel KDF1 variant-related NSTA in Thai people. The genotype-phenotype correlates suggest a distinctive pattern and tooth agenesis of KDF1-related NSTA.

The aim of this systematic review was to describe the clinical and genetic features of syndromes showing oligodontia as a sign. The review was performed according to the PRISMA 2020 checklist guidelines, and the search was conducted using PubMed, Scopus, Lilacs, Web of science, Livivo, and EMBASE and supplemented by a gray literature search on Google Scholar and ProQuest, applying key terms relevant to the research questions. The systematic review identified 47 types of syndromes in 83 studies, and the most common was hypohidrotic ectodermal dysplasia, which was reported in 24 patients in 22 studies. Other common syndromes that reported oligodontia included Axenfeld-Rieger syndrome, Witkop\'s syndrome, Ellis-van Creveld syndrome, blepharocheilodontic syndrome, and oculofaciocardiodental syndrome. The X-linked mode of inheritance was the most reported (n = 13 studies), followed by the autosomal dominant (n = 13 studies). The review describes the main syndromes that may have oligodontia as a clinical sign and reinforces the need for orodental-facial examining for adequate diagnosis and treatment of the affected patients. Molecular analysis in order to better understand the occurrence of oligodontia is imperative.

Mutations in PAX9 are the most common genetic cause of tooth agenesis (TA). The aim of this study was to systematically review the profiles of the TA and PAX9 variants and establish their genotype-phenotype correlation. Forty articles were eligible for 178 patients and 61 mutations (26 in frame and 32 null mutations). PAX9 mutations predominantly affected molars, mostly the second molar, and the mandibular first premolar was the least affected. More missing teeth were found in the maxilla than the mandible, and with null mutations than in-frame mutations. The number of missing teeth was correlated with the locations of the in-frame mutations with the C-terminus mutations demonstrating the fewest missing teeth. The null mutation location did not influence the number of missing teeth. Null mutations in all locations predominantly affected molars. For the in-frame mutations, a missing second molar was commonly associated with mutations in the highly conserved paired DNA-binding domain, particularly the linking peptide (100% prevalence). In contrast, C-terminus mutations were rarely associated with missing second molars and anterior teeth, but were commonly related to an absent second premolar. These finding indicate that the mutation type and position contribute to different degrees of loss of PAX9 function that further differentially influences the manifestations of TA. This study provides novel information on the correlation of the PAX9 genotype-phenotype, aiding in the genetic counseling for TA.

Oligodontia is a developmental dental anomaly defined by the absence of 6 or more permanent teeth, excluding the third molars. We performed a review with a systematic approach and proposed a guideline for the choice of the bone augmentation surgery. The different bone augmentation technique terms were searched in the PubMed and Science Direct database. Clinical studies were eligible if they reported on pre-implant surgery in patients with oligodontia. The database search yielded 400 studies after duplicates removed. Thirty studies were finally included, involving 410 patients. Sixty-three sinus lifts were performed in 37 patients with no failure. Thirteen out of 33 patients with iliac bone transplantation and two out of 24 with parietal bone transplantation had resorption, one out of 4 patients who received allogeneic bone block had complete failure. Seventy-eight patients underwent guided bone regeneration, none had bone loss. No failure was found with the alveolar distraction osteogenesis technique. Four out of thirteen patients developed permanent hypoesthesia after inferior alveolar nerve transposition. The cumulative implant survival rate was 94.4% after bone augmentation procedures. Extensive edentulous areas should be grafted with parietal bone, as iliac grafts present a greater risk of resorption. Smaller edentulous areas should be treated by endobuccal harvesting or guided bone regeneration. Osteogenesis distraction and nerve transposition are effective surgeries for medium-to-large mandibular edentulous spaces. The implant survival rate is not significantly different between implants placed in grafted and nongrafted bone, the appropriate choice of bone augmentation technique can reduce the risk of peri‑implant bone resorption.

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).
To assess the link between TA and the development of cancer.
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.
The primary outcome was the relationship between TA and cancer. The secondary outcome was to identify the genetic correlation between TA and cancer.
Study selection, data extraction and risk of bias assessment were performed independently and induplicate by two reviewers, with disputes resolved by a third reviewer.
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).
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.
PROSPERO (CRD42020139751).

Ectodermal dysplasia (ED) is a congenital disorder primarily affecting the ectodermal tissue, with infrequent dysfunction of mesodermally derived tissues. Clinically, there are two major forms seen, hypohidrotic/Christ-Siemens-Touraine syndrome and hidrotic/Clouston syndrome, depending on the number and function of sweat glands. A multidisciplinary treatment protocol is usually followed and necessitates collective efforts by medical and dental professionals. Dental intervention should be done as early as possible to ameliorate the patient\'s esthetics and enhance the emotional and psychological quotient in these patients. This case report aims to highlight a rare and interesting report of hypohidrotic ED in a young female patient with a possible autosomal recessive inheritance pattern.

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.

Tooth agenesis in the reduction of tooth number which includes hypodontia, oligodontia and anodontia is caused by disturbances and gene mutations that occur during odontogenesis. To date, several genetic mutations that unlock the causes of non-syndromic tooth agenesis are being discovered; these have been associated with certain illnesses because tooth development involves the interaction of several genes for tooth epithelium and mesenchyme odontogenesis. Mutation of candidate genes PAX9 and MSX1 have been identified as the main causes of hypodontia and oligodontia; meanwhile, AXIN2 mutation is associated with anodontia. Previous study using animal models reported that PAX9-deficient knockout mice exhibit missing molars due to an arrest of tooth development at the bud stage. PAX9 frameshift, missense and nonsense mutations are reported to be responsible; however, the most severe condition showed by the phenotype is caused by haploinsufficiency. This suggests that PAX9 is dosage-sensitive. Understanding the mechanism of genetic mutations will benefit clinicians and human geneticists in future alternative treatment investigations.

Paired box 9 (PAX9) is one of the best-known transcription factors involved in the development of human dentition. Mutations in PAX9 gene could, therefore, seriously influence the number, position and morphology of the teeth in an affected individual. To date, over 50 mutations in the gene have been reported as associated with various types of dental agenesis (congenitally missing teeth) and other inherited dental defects or variations. The most common consequence of PAX9 gene mutation is the autosomal-dominant isolated (non-syndromic) oligodontia or hypodontia. In the present review, we are summarizing all known PAX9 mutations as well as their nature and precise loci in the DNA sequence of the gene. Where necessary, we have revised the loci of the mutations in line with the reference sequence of the PAX9 gene as it appears in the current DNA databases.