Non-syndromic Oligodontia Research Articles

A novel PAX9 variant in a Chinese family with non-syndromic oligodontia and genotype-phenotype analysis of PAX9variants.

This study aimed to identifyPAX9variants in non-syndromic tooth agenesis families of China, as well as to analyze the genotype⁃phenotype of non-syndromic tooth agenesis caused by PAX9variants, which can provide a basis for the genetic diagnosis of tooth agenesis. We collected the data of 44 patients with non-syndromic oligodontia who underwent treatment at Stomatological Hospital of Hebei Medical University between 2018 and 2023. Whole-exome sequencing was performed on the peripheral blood of the proband and its core family members, and the variants were verified by Sanger sequencing. Pathogenicity analysis and function prediction of the variants were performed using bioinformatics tools. The correlation between the genotype of PAX9 variant and its corresponding phenotype was examined by reviewing 55 publications retrieved from PubMed. The studies involved 232 tooth agenesis patients with PAX9 variants. A novel PAX9 c.447delG (p.Pro150Argfs*62) and a reported PAX9 c.406C>T (p.Gln136*) were identified in two Chinese families. Through bioinformatics analysis and three-dimensional structural modeling, we postulated that the frameshift variant was pathogenic. The outcome was the premature cessation of PAX9 protein, which caused severe structural and functional deficiencies. Summarizing the PAX9 genotype-phenotype relationship revealed that patients carrying the PAX9 variant commonly led to loss of the second molars. We identified the novel PAX9 c.447delG (p.Pro150Argfs*62) in a Chinese family of non-syndromic oligodontia, expanding the known variant spectrum of PAX9. The most susceptible tooth position for PAX9 variants of tooth agenesis was the second molars and the deciduous molars during the deciduous dentition.

Treatment strategy for patient with non-syndromic tooth agenesis: a case report and literature review

BackgroundNon-syndromic tooth agenesis (NSTA) is a type of ectodermal dysplasia (ED) in which patients with non-syndromic oligodontia may only affect teeth. No pathological findings were found in other tissues of the ectodermal. Herein, we report a case of a NSTA patient with severe dental anxiety and poor oral health.Case presentationA 5-year-old boy without systemic diseases presented as a patient with oligodontia, extensive caries, and periapical periodontitis. Molecular genetic analysis found a mutation in the Ectodysplasin A (EDA) gene, confirming the diagnosis of NSTA.ConclusionTooth agenesis (TA) is the most common ectodermal developmental abnormality in humans. Non-syndromic oligodontia patients often seek treatment in the department of stomatology. Because of their complex oral conditions, these patients should be provided with a systematic and personalized treatment plan.

Novel PAX9 Mutations Causing Isolated Oligodontia.

Hypodontia, i.e., missing one or more teeth, is a relatively common human disease; however, oligodontia, i.e., missing six or more teeth, excluding the third molars, is a rare congenital disorder. Many genes have been shown to cause oligodontia in non-syndromic or syndromic conditions. In this study, we identified two novel PAX9 mutations in two non-syndromic oligodontia families. A mutational analysis identified a silent mutation (NM_006194.4: c.771G>A, p.(Gln257=)) in family 1 and a frameshift mutation caused by a single nucleotide duplication (c.637dup, p.(Asp213Glyfs*104)) in family 2. A minigene splicing assay revealed that the silent mutation resulted in aberrant pre-mRNA splicing instead of normal splicing. The altered splicing products are ones with an exon 4 deletion or using a cryptic 5' splicing site in exon 4. Mutational effects were further investigated using protein expression, luciferase activity assay and immunolocalization. We believe this study will not only expand the mutational spectrum of PAX9 mutations in oligodontia but also strengthen the diagnostic power related to the identified silent mutation.

Clinical analysis of nonsyndromic oligodontia phenotypes.

To provide references, this study investigated the clinical characteristics of patients with nonsyndromic oligodontia. 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. 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. 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.

Characterization of novel MSX1 variants causally associated with non-syndromic oligodontia in Chinese families.

MSX1 (OMIM #142983) is crucial to normal dental development, and variants in MSX1 are associated with dental anomalies. The objective of this study was to characterize the pathogenicity of novel MSX1 variants in Chinese families with non-syndromic oligodontia (NSO). Genomic DNA was extracted from individuals representing 35 families with non-syndromic oligodontia and was analyzed by Sanger sequencing and whole-exome sequencing. Pathogenic variants were screened via analyses involving PolyPhen-2, Sorting-Intolerant from Tolerant, and MutationTaster, and conservative analysis of variants. Patterns of MSX1-related NSO were analyzed. MSX1 structural changes suggested functional consequences invitro. Three previously unreported MSX1 heterozygous variants were identified: one insertion variant (c.576_577insTAG; p.Gln193*) and two missense variants (c. 871T>C; p.Tyr291His and c. 644A>C; p.Gln215Pro). Immunofluorescence analysis revealed abnormal subcellular localization of the p.Gln193* MSX1 variant. In addition, we found that these MSX1 variants likely lead to the loss of second premolars. Three novel MSX1 variants were identified in Chinese Han families with NSO, expanding the MSX1 variant spectrum and presenting a genetic origin for the pathogenesis detected in patients and their families.

Psychosocial and Behavioral Impact of Three Clinical Presentations of Oligodontia in a Tertiary Hospital.

To investigate the psychosocial and behavioral impact of oligodontia across three presentation types and determine if presentation type can infer impact. Thirty patients who had been diagnosed and treated for oligodontia between 2006 and 2021 were identified from hospital records. Patients received two questionnaires: (1) a modified version of a condition-specific questionnaire- the Cleft Research Questionnaire (CRQ), used to investigate demographic, life, and treatment details and impacts-and (2) the Oral Health Impact Profile (OHIP-14), used to investigate the oral health-related quality of life. Patients were assigned to three presentations (Types 1 to 3) of oligodontia, identified according to the edentulous space present and complexity of prosthodontic treatment required. The hypothesis that there is a relationship between oligodontia type and study variables was tested. Twenty-two questionnaires were completed and returned. There were 13 men and 9 women. The age range was from 16 to 32 years. In total, 18 patients had nonsyndromic oligodontia and 4 had oligodontia associated with anhidrotic ectodermal dysplasia (AED). The main areas of impact were patient-reported: life less satisfying (64.5%, n &#61; 14; pretreatment), making friends (45%, n &#61; 10), school participation (45%, n &#61; 10), and public speaking (45%, n &#61; 10). No relationship was discovered between the degree of physical effect of the presentation type and study variables, including the degree of psychosocial impact or life satisfaction. Oligodontia can have a negative functional and social impact on a patient prior to prosthodontic treatment. Prosthodontic treatment improved the life satisfaction for most patients. Psychosocial outcomes could not be inferred by the presentation type of oligodontia.

Mesiodistal angulation and developmental stages of unerupted mandibular second premolars in nonsyndromic oligodontia

Oligodontia is a serious developmental dental anomaly that requires long-term multidisciplinary treatment, but its clinical characteristics are not well understood because it is rare. This study evaluated the mesiodistal angulation and developmental stages of unerupted mandibular second premolars (MnP2s) in orthodontic patients with nonsyndromic oligodontia. Thirty-seven patients with oligodontia with at least 1 unerupted MnP2 in Demirjian's developmental stages between D and G were selected. Age- and sex-matched patients without tooth agenesis, excluding third molars, were selected as the control group. Mesiodistal angulation between the long axis of the available MnP2 and the mandibular plane was measured on panoramic radiographs. The MnP2 was significantly more distally angulated in the oligodontia group than in the control group. The developmental stage of the MnP2 in the oligodontia group was significantly delayed (1.04 ± 0.26 years; 95% confidence interval, 0.53-1.55 years). No correlation between the mesiodistal angulation and the developmental stage of the MnP2 was found in both groups. Significant distal angulation and delayed developmental stages of MnP2s were found in patients with nonsyndromic oligodontia compared with age- and sex-matched patients without agenesis of permanent teeth, excluding third molars. However, no significant correlation was found between them. Regardless of the severity of the distal angulation of MnP2, observing delayed dental development in each patient is important.

Phenotypic characteristics of taurodontism and a novel WNT10A variant in non-syndromic oligodontia family

ObjectiveVariants in wingless-type MMTV integration site family member 10A (WNT10A) have been proposed to be the most common cause of non-syndromic oligodontia (NSO). The goal of the present study was to identify the novel WNT10A variants in Chinese families with NSO. DesignClinical data were collected from 39 families with oligodontia admitted to the Hospital of Stomatology Hebei Medical University (China) from 2016 to 2022. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify WNT10A variants in three families with non-syndromic oligodontia. Amino acid conservation analysis and protein conformational analysis were conducted for the WNT10A variant. Genotype-phenotype analysis was performed on the previously reported WNT10A variants related to NSO. ResultsWe found a novel heterozygous WNT10A variant c.1127 G>A (p.Cys376Tyr) and two reported heterozygous variants c.460 C>A (p.Leu154Met) and c.511 C>T (p.Arg171Cys). Structural modeling showed that the novel WNT10A variant was located in a highly conserved domain, which led to structural damage of WNT10A protein. In addition, we found that the phenotype of the WNT10A variants affected the maxillary second premolars, followed by the mandibular second premolars, and rarely affected the maxillary central incisor. Herein, it is the first time to report that NSO patients with WNT10A monoallele mutation carry taurodontism phenotype and 6.1% prevalence of taurodontism in WNT10A-related NSO patients. ConclusionsOur results demonstrated that the novel variant c.1127 G>A (p.Cys376Tyr) of WNT10A causes NSO. The present study expanded the known variation spectrum of WNT10A and provided valuable information for genetic counseling of families.

Five-Year Follow-Up of a Child with Non-Syndromic Oligodontia from before the Primary Dentition Stage: A Case Report

Congenital absence of teeth is a major dental abnormality in pediatric dentistry and the absence of six or more teeth is defined as oligodontia. Few reports of patients with non-syndromic oligodontia without systemic disease have continued dental follow-up from an early age. We performed the five-year follow-up from before the eruption of the primary dentition of a Japanese child with non-syndromic oligodontia and analyzed changes in dental arch growth. At the oral examination at the age of 1 year and 2 months, eight primary incisors were congenitally absent. Therefore, we made dentures for the patient at the age of 3 years and 4 months. From the age of 5 years and 1 month, the child received articulation training for dysarthria from a speech therapist to improve the function and appearance of the oral cavity. Measurement of the patient's dental models revealed a particularly narrow dental arch, especially between the primary canines. Our findings highlight the importance of treatment for patients with non-syndromic oligodontia from an early age by multiple medical professionals, recognizing that the missing teeth affect the growth of the maxillofacial region.

Genotype-phenotype pattern analysis of pathogenic PAX9 variants in Chinese Han families with non-syndromic oligodontia.

Background: Non-syndromic oligodontia is characterized by the absence of six or more permanent teeth, excluding third molars, and can have aesthetic, masticatory, and psychological consequences. Previous studies have shown that PAX9 is associated with autosomal dominant forms of oligodontia but the precise molecular mechanisms are still unknown. Methods: Whole-exome and Sanger sequencing were performed on a cohort of approximately 28 probands with NSO, for mutation analysis. Bioinformatic analysis was performed on the potential variants. Immunofluorescence assay, western blotting, and qPCR were used to explore the preliminary functional impact of the variant PAX9 proteins. We reviewed PAX9-related NSO articles in PubMed to analyze the genotype-phenotype correlations. Results: We identified three novel PAX9 variants in Chinese Han families: c.152G>T (p.Gly51Val), c.239delC (p.Thr82Profs*3), and c.409C>T (q.Gln137Ter). In addition, two previously reported missense variants were identified: c.140G>C (p.Arg47Pro) and c.146C>T (p.Ser49Leu) (reference sequence NM_006194.4). Structural modeling revealed that all missense variants were located in the highly conserved paired domain. The other variants led to premature termination of the protein, causing structural impairment of the PAX9 protein. Immunofluorescence assay showed abnormal subcellular localizations of the missense variants (R47P, S49L, and G51V). In human dental pulp stem cells, western blotting and qPCR showed decreased expression of PAX9 variants (c.140G>C, p.R47P, and c.152G>T, p.G51V) compared with the wild-type group at both the transcription and translation levels. A review of published papers identified 64 PAX9 variants related to NSO and found that the most dominant feature was the high incidence of missing upper second molars, first molars, second premolars, and lower second molars. Conclusion: Three novel PAX9 variants were identified in Chinese Han families with NSO. These results extend the variant spectrum of PAX9 and provide a foundation for genetic diagnosis and counseling.

A Multidisciplinary Approach for Full-Mouth Rehabilitation in Oligodontia: A Clinical Report.

The absence of teeth in children due to congenital agenesis, syndromic or not, could lead to oral dysfunctions with general repercussions and sociopsychological problems. This case was a 17-year-old girl with severe nonsyndromic oligodontia who was missing 18 permanent teeth and had a class III skeletal pattern. It was challenging to provide functional and esthetically pleasing results in terms of temporary rehabilitation during growth and long-term rehabilitation in adulthood. This case report described the originality of the realization steps of oligodontia management, in 2 main parts. The osseous time by the LeFort 1 osteotomy advancement with simultaneous parietal and xenogenic bone grafting to improve a large bimaxillary bone volume, allowing future early implant placement by absence of growth of adjacent alveolar processes. The prosthetic rehabilitation with the conservation of natural teeth for proprioception and the use of a screw-retained polymethyl-methacrylate immediate prostheses to evaluate the needed vertical dimensional changes and make functional and esthetic results more predictable. This article could be retained as a technical note to manage this kind of case with the intellectual workflow and the difficulties encountered.

Novel WNT10A variant in a Japanese case of nonsyndromic oligodontia

Congenital tooth agenesis is one of the most common anomalies in humans. Many genetic factors are involved in tooth development, including MSX1, PAX9, WNT10A, and LRP6. Thus, mutations in these genes can cause congenital tooth agenesis in humans. In this study, we identified a novel nonsense WNT10A variant, NM_025216.3(WNT10A_v001):c.1090A > T, which produces a C-terminal truncated gene product, p.(Lys364*), in a sporadic form of congenital tooth agenesis. The variant was not found in the healthy parents and thus was considered to cause congenital tooth agenesis in the case.

BMPR2 Variants Underlie Nonsyndromic Oligodontia.

Oligodontia manifests as a congenital reduction in the number of permanent teeth. Despite the major efforts that have been made, the genetic etiology of oligodontia remains largely unknown. Bone morphogenetic protein receptor type 2 (BMPR2) variants have been associated with pulmonary arterial hypertension (PAH). However, the genetic significance of BMPR2 in oligodontia has not been previously reported. In the present study, we identified a novel heterozygous variant (c.814C > T; p.Arg272Cys) of BMPR2 in a family with nonsyndromic oligodontia by performing whole-exome sequencing. In addition, we identified two additional heterozygous variants (c.1042G > A; p.Val348Ile and c.1429A > G; p.Lys477Glu) among a cohort of 130 unrelated individuals with nonsyndromic oligodontia by performing Sanger sequencing. Functional analysis demonstrated that the activities of phospho-SMAD1/5/8 were significantly inhibited in BMPR2-knockout 293T cells transfected with variant-expressing plasmids, and were significantly lower in BMPR2 heterozygosity simulation groups than in the wild-type group, indicating that haploinsufficiency may represent the genetic mechanism. RNAscope in situ hybridization revealed that BMPR2 transcripts were highly expressed in the dental papilla and adjacent inner enamel epithelium in mice tooth germs, suggesting that BMPR2 may play important roles in tooth development. Our findings broaden the genetic spectrum of oligodontia and provide clinical and genetic evidence supporting the importance of BMPR2 in nonsyndromic oligodontia.

Novel PAX9 compound heterozygous variants in a Chinese family with non-syndromic oligodontia and genotype-phenotype analysis of PAX9 variants.

Studies have reported that >91.9% of non-syndromic tooth agenesis cases are caused by seven pathogenic genes. To report novel heterozygous PAX9 variants in a Chinese family with non-syndromic oligodontia and summarize the reported genotype-phenotype relationship of PAX9 variants. We recruited 28 patients with non-syndromic oligodontia who were admitted to the Hospital of Stomatology Hebei Medical University (China) from 2018 to 2021. Peripheral blood was collected from the probands and their core family members for whole-exome sequencing (WES) and variants were verified by Sanger sequencing. Bioinformatics tools were used to predict the pathogenicity of the variants. SWISS-MODEL homology modeling was used to analyze the three-dimensional structural changes of variant proteins. We also analyzed the genotype-phenotype relationships of PAX9 variants. We identified novel compound heterozygous PAX9 variants (reference sequence NM_001372076.1) in a Chinese family with non-syndromic oligodontia: a new missense variant c.1010C>A (p.T337K) in exon 4 and a new frameshift variant c.330_331insGT (p.D113Afs*9) in exon 2, which was identified as the pathogenic variant in this family. This discovery expands the known variant spectrum of PAX9; then, we summarized the phenotypes of non-syndromic oligodontia with PAX9 variants. We found that PAX9 variants commonly lead to loss of the second molars.

Novel LRP6 Mutations Causing Non-Syndromic Oligodontia.

The process of tooth formation is a series of reciprocal interactions between the ectoderm and mesoderm, and it is believed that many genetic factors are involved in this complex process. More than a dozen genes have been identified in non-syndromic tooth agenesis; however, the genetic etiology underlying tooth agenesis is not fully understood yet. In this study, we identified two novel LRP6 mutations in two non-syndromic oligodontia families. Both probands had 16 and 17 missing teeth in their permanent dentition. Mutational analysis identified a de novo frameshift mutation by a 1-bp insertion in exon 9 (NM_002336.2: c.1870dupA, p.(Met624Asnfs*29)) and a splicing donor site mutation in intron 8 (c.1762+2T>C). An in vitro splicing assay confirmed the deletion of exon 8, and the deletion would result in a frameshift. Due to the premature termination codons introduced by the frameshift, both mutant transcripts would be degraded by nonsense-mediated mRNA decay, resulting in haploinsufficiency.

Aesthetic rehabilitation of a nonsyndromic oligodontia patient - A conservative treatment approach

Oligodontia, a developmental dental anomaly, characterized by the congenital absence of more than six permanent teeth except the third molarsleading to functional, aesthetic,and psychological problems, when the anterior region is involved.This case report describes a multidisciplinary treatment approach of a 21 year old female patient with missing 6 permanent teeth. Microdontia with respect to mandibular canine was observed and retained deciduous mandibular canine was seen on intraoral examination. The first phase of treatment wasextraction of maxillary central incisors followed by alveoloplasty. The second phase of treatment included intentional pulp space therapy followed by prosthetic restoration of the missing teeth with fixed partial denture as a quick solution for the patients who reject more time-consuming procedure.

Detection of novel variant and functional study in a Chinese family with nonsyndromic oligodontia.

To investigate the pathogenic gene of a patient with nonsyndromic oligodontia, and analyze its possible pathogenic mechanism. The variant was detected by whole exome sequencing (WES) and Sanger sequencing in a family with oligodontia. Bioinformatic and structural analyses were used to analyze variant. Functional studies including western blotting and immunofluorescent analyses and luciferase reporter assay were conducted to explore the functional effects. We identified a novel frameshift variant of PAX9 (c.491-510delGCCCT-ATCACGGCGGCGGCC, p.P165Qfs*145) outside the DNA-binding domain causing an autosomal-dominant nonsyndromic oligodontia in a Chinese family. Bioinformatic and structural analyses revealed that the variant is pathogenic and conserved evolutionarily, and the changes might affect protein stability or folding. Functional studies demonstrate dramatically reduced ability in activating transcription activity of BMP4 promoter and a marked decrease in protein production, as evaluated by western blotting and immunofluorescent analyses. We found a novel frameshift variant of PAX9 causing nonsyndromic oligodontia in a Chinese family. Our findings indicate that frameshift variants cause loss of function of PAX9 protein during the patterning of the dentition and the subsequent tooth agenesis, providing new molecular insights into the role of frameshift variant of PAX9 and broaden the pathogenic spectrum of PAX9 variants.

Interdisciplinary dental management of patient with oligodontia and maxillary hypoplasia: a case report

BackgroundThe craniofacial developmental abnormality can significantly complicate the oral rehabilitation of patients with oligodontia. This case report describes an interdisciplinary approach that took 7 years to successfully treat a young patient with non-syndromic oligodontia and midface deficiency.Case presentationA 14-year-old patient with complex oral and maxillofacial conditions and diagnosis of oligodontia presented to our clinic. In addition to 4 retained deciduous teeth and congenitally missing 10 permanent teeth, dentofacial findings included maxillary and malar deficiency with a concave facial profile, Angle Class III malocclusion, and poor dental esthetics. The interdisciplinary treatment included pre-surgical orthodontic decompensation, high Le Fort I maxillary osteotomy, postsurgical orthodontic therapy, osseous ridge augmentation using recombinant human bone morphogenetic protein-2 (rhBMP-2), interim removable partial denture, dental implant installation, interim implant prostheses, and final prosthetic rehabilitation.ConclusionsThe successful treatment of patients with oligodontia and complex dentofacial abnormalities requires the close and orderly collaboration among orthodontist, oral maxillofacial surgeon, and prosthodontist. Within the limitations of this case report, presented interdisciplinary approaches may optimize the oral rehabilitation outcome in patients with similar clinical challenges. A prospective clinical investigation is desired to verify the benefit of presented interdisciplinary approach.

Sexual dimorphism in the consecutive tooth agenesis patterns of patients with non-syndromic oligodontia

ABSTRACT Purpose To compare consecutive tooth agenesis (CTA) patterns between female and male patients with non-syndromic oligodontia. Materials and Methods Panoramic radiographs of 311 orthodontic patients (194 females and 117 males) with non-syndromic oligodontia were evaluated, and permanent teeth excluding third molars were examined. The number and prevalence of tooth agenesis and the number of agenetic teeth associated with CTA were calculated for each tooth. Numbers of CTAs in each dental arch and per patient, and numbers of agenetic teeth associated with the longest CTA were evaluated and compared between the female and male patients. The CTA type of each dental arch was categorized as follows: (I) anterior teeth only; (II) posterior teeth only; (IIIA) continuously in anterior and posterior teeth; (IIIB) separated in anterior and posterior teeth; and (IV) multiple types. The types were then compared between the female and male patients. Results Male patients more frequently had at least one CTA than female patients. The prevalence of Types I and IIIA in the mandibular arch was significantly higher in males than in females. Conclusion Although there was no significant sex difference in the overall severity, males with non-syndromic oligodontia were more likely than females to have CTA indicating local severity in the mandibular anterior teeth.

Maxillofacial morphological characteristics in growing orthodontic patients with non-syndromic oligodontia.

Patients with oligodontia frequently show different types of malocclusions. However, how oligodontia affects the maxillofacial growth remains uncertain. This study aimed to investigate the maxillofacial morphological characteristics in growing patients with oligodontia. The study subjects included 33 Japanese children with non-syndromic oligodontia (14 boys and 19 girls; mean age: 10.2years) who visited the orthodontic clinic of Fukuoka Dental College Medical and Dental Hospital from 1999 to 2019. Cephalometric analyses were performed, and the variables measured in each subject were converted into Z scores in relation to the mean and standard deviation of the Japanese norms matched for growth stage. The one-sample t-test or Wilcoxon signed-rank test was performed to compare the mean scores in the patients with oligodontia with those of the Japanese norms. Compared with the Japanese norms, patients with oligodontia showed a smaller convexity and larger A-B plane and SNB angles. The Frankfort-mandibular plane and gonial angles were smaller, whereas the height of the ramus was larger. The vertical height of the alveolar bone in the maxillary and mandibular incisors and molar areas was smaller in patients with oligodontia. Patients with oligodontia showed Class III skeletal tendency with mandibular prognathism and flattened mandibular plane with a smaller gonial angle. These maxillofacial morphological features can be induced by a deficiency in the vertical growth of the alveolar bone in the maxillary and mandibular molar areas due to the lack of tooth germs.