Pycnodysostosis: Characteristics of teeth, mouth and jaws.

OBJECTIVES: To describe the clinical and radiographic oro-dental characteristics of patients with pycnodysostosis (PDO). MATERIALS & METHODS: A short interview and clinical examination of seven patients with PDO were performed as well as assessment of the temporomandibular joints and masticatory muscles using the diagnostic criteria for temporomandibular disorders, DC-TMD form. A full set of records were taken including photos and intraoral scan. Finally, existing cone beam computed tomography (CBCT) images and radiographs were also studied. RESULTS: All patients presented with bimaxillary micrognathia, five had a convex profile, and two had a straight profile. In addition, posterior open bite, Angle Class III molar relation with accompanying anterior crossbite and a grooved median palate were common findings. No patient showed symptoms of temporomandibular disorder (TMD) apart from some clicking. Finally, the main radiographic findings were the obtuse mandibular angle, the frontal bossing, the elongation of the coronoid/condylar process and the presence of hypercementosis with obliterated pulp chambers. CONCLUSION: The examined patients with PDO were characterized by dental crowding, malocclusion (anterior crossbite, posterior open bite), hypercementosis, obliterated pulp chambers and deviations in mandibular morphology. In conclusion, patients with PDO have a specific need for dental and orthodontic monitoring with focus on crowding and posterior open bite. The patients will benefit from a long-term orthodontic plan including extractions.

Craniofacial morphology in adults with osteogenesis imperfecta-A cross-sectional study.

OBJECTIVES: The aim of this study was to compare the craniofacial and neurocranial morphology of adults with osteogenesis imperfecta (OI) with controls and to elucidate whether osseous origin impacts on morphological deviations in OI. MATERIALS AND METHODS: Fifty-four adults (mean age 45.8) with OI type I, 14 adults (mean age 42.6) with OI types III/IV and 49 adult controls (mean age 41.0) were included. All participants had European ethnicity. Cranial morphology was assessed by 2D-cephalometry. Comparison between groups was made by multiple regression analyses. RESULTS: Comparison between OI groups and controls: (1) Dimension of the maxilla and mandible, respectively was reduced (P < .01), and in relation to the posterior cranial base, the maxilla was retro-positioned (P < .001), and the mandible was prognathic (P < .001). (2) The anterior face height was reduced (P < .04), and in OI types III/IV only, the maxilla was posteriorly inclined (P < .001). (3) Anterior cranial base (P < .001) and the dimension sella-frontale (P < .02) were short. (4) The sagittal dimension of the posterior cranial fossa was increased (P < .01), and the vertical dimension was reduced (P < .01). CONCLUSIONS: Adults with OI had a hypoplastic, retro-positioned and posteriorly inclined maxilla, a hypoplastic and forward-positioned mandible, and a reduced anterior face height. Deviations were seen in morphology of the posterior cranial fossa. The impact of OI on cranial morphology was generally more evident in OI type III/IV than in OI type I. OI impacts on osseous cranial structures irrespective of bony origin being intramembranous or endochondral.

Obstructive sleep apnoea in pycnodysostosis: A three-dimensional upper airway analysis.

AIM: To assess the upper airway (UA) morphology in patients with pycnodysostosis with a 3D analysis, compare results with normative data and investigate the correlation of the total volume (TV) with other UA morphology variables. MATERIALS AND METHODS: Cone beam computed tomography (CBCT) images of eight Danish patients with pycnodysostosis (4 males and 4 females with a mean age of 31.8 years, SD: 16.3 years) were analyzed using Mimics® (Materialise® ) and compared with a sex- and age-matched control group (6 males and 8 females with a mean age of 33.6 years, SD: 18.6 years). RESULTS: The distance from the tip of the epiglottis (E) to the Frankfurt horizontal plane (Fp) was significantly shorter in the pycnodysostosis group (P < .042). Regarding the cross-sectional measurements, at the 'maximum constriction' (P < .005), the 'upper airway limit' (P < .001) and the 'lower airway limit' (P < .035) cross-sections were significantly smaller in the pycnodysostosis group. The volumes 'nasopharynx' (P < .002) and 'total airway' (TV) (P < .01) were also significantly smaller. CONCLUSION: Patients with pycnodysostosis have a reduced total airway as well as nasopharyngeal volume compared with matched controls. Additionally, they have a reduced cross-sectional area in the upper and lower borders of the UA, and the area of maximum constriction is also reduced. These factors might explain the high prevalence of obstructive sleep apnoea in pycnodysostosis. Total airway is positively correlated with total length and cross-sections at all levels including the maximum constriction area as well as the anteroposterior dimension at the upper and lower airway borders.

Three-dimensional analysis of craniofacial morphology in patients with pycnodysostosis.

OBJECTIVE: To perform a 3D cephalometric analysis of the craniofacial characteristics of patients with pycnodysostosis and compare this with a matched control group. SETTING AND SAMPLE POPULATION: This cross-sectional descriptive study assessed eight CBCTs obtained in patients with pycnodysostosis (4 males, 4 females, mean age: 31.8 years). MATERIALS AND METHODS: Eight Danish patients with pycnodysostosis were seen at the University's Orthodontic Clinic. All CBCTs were analysed using the Mimics 21.0 software (Materialise®, Belgium) and compared with a control group (6 males, 8 females, mean age: 33.6 years). RESULTS: Interclass correlation coefficient showed excellent intra-rater reliability (> 0.93). All measurements in the 3D cephalometric analysis revealed statistical significance (P < .05) when compared with controls. Patients with pycnodysostosis generally had significantly smaller maxilla in the transverse (P < .001), sagittal (P < .002) and vertical (P < .001) dimensions. Their mandibles were also smaller vertically (P < .001) and in length (P < .001). Gonial angle was significantly larger than controls (P < .001), while mandibular volumes were considerably smaller (P < .001). CONCLUSION: Patients with pycnodysostosis have significantly smaller jaws in the vertical, sagittal and transverse dimensions compared with controls. Furthermore, the gonial angle was significantly larger, while the volume of the mandible was significantly smaller.

Oral health-related quality of life in X-linked hypophosphataemia and osteogenesis imperfecta.

X-linked hypophosphataemia (XLH) and osteogenesis imperfecta (OI) are rare congenital disorders characterised by skeletal dysplasia. The two disorders may include dental anomalies potentially affecting individual well-being. The aims of study were (a) to assess the oral health-related quality of life (OHRQoL) in Danish adults with XLH or OI, and (b) to compare the results of the groups. A cross-sectional study including 35 adults with XLH, 56 adults with OI type I and 17 adults with OI types III-IV was conducted. The OHRQoL was assessed by the 49-item version of the questionnaire Oral Health Impact Profile (OHIP). Summed domain scores (seven) were compared between XLH and OI groups. Prevalence of severe impact on OHRQoL (scores 3-4) was compared between groups. The median scores in XLH group exceeded the medians in OI (P < .05) in the domains functional limitation (XLH:6.5; OI:4.0), pain (XLH:9.5; OI:5.0), psychological discomfort (XLH:5.5; OI:2.0), psychological disability (XLH:2.0; OI:0.0), handicap (XLH:2.0; OI:0.0) and total OHIP (XLH:35.0; OI:14.0). Differences in domains physical disability (XLH: 4.0; OI: 1.0) and social disability (XLH: 0.0; OI: 0.0) were not significant. Prevalence of severe impact on OHRQoL in the XLH group significantly exceeded the level in OI group in the domains functional limitation (XLH: 59%; OI: 35%), psychological discomfort (XLH: 38%; OI: 20%) and physical disability (XLH: 32%; OI: 13%). In conclusion, adults with XLH experience a higher negative impact on their OHRQoL than adults with OI. Only to a minor degree, individuals with OI types III-IV experience a higher impact on OHRQoL than individuals with OI type I.

Novel phenotype of syndromic premature ovarian insufficiency associated with TP63 molecular defect.

There is growing evidence that TP63 is associated with isolated as well as syndromic premature ovarian insufficiency (POI). We report two adolescent sisters diagnosed with undetectable ovaries, uterine hypoplasia, and mammary gland hypoplasia. A novel paternally inherited nonsense variant in TP63 [NM_003722.4 c.1927C > T,p.(Arg643*)] in exon 14 was identified by exome sequencing. One of the syndromes linked to TP63 is limb mammary syndrome (LMS), an autosomal dominant inherited disorder characterized by ectrodactyly, hypoplasia of mammary-gland and nipple, lacrimal duct stenosis, nail dysplasia, dental anomalies, cleft palate and/or cleft lip and absence of skin and hair defects. The TP63 variant segregated with symptoms of LMS in the family, however, no affected individual had limb defects. The phenotype reported here represents a novel syndromic phenotype associated with TP63. Reported cases with TP63 associated POI are reviewed.

Dental anomalies and orthodontic characteristics in patients with pseudohypoparathyroidism.

BACKGROUND: Pseudohypoparathyroidism (PHP) is a rare and inherited disease caused by mutations in the GNAS-gene or upstream of the GNAS complex locus. It is characterized by end-organ resistance to PTH, resulting in hypocalcemia and hyperphosphatemia. We aimed to investigate the dental anomalies according to tooth types and the orthodontic characteristics of patients with PHP. METHODS: Using a cross-sectional design, 29 patients (23 females) with PHP, living in Denmark, were included, and their clinical intraoral photos and radiographs were examined. RESULTS: Pulp calcification was found in 76% of the patients. Blunting of root apex was present in 55% and shortening of root in 48% of the examined patients. Blunting and shortening of roots were seen more often in premolars than in other tooth types (pboth < 0.01). Crowding of lower anterior teeth was frequently observed (36%) as well as diastema in the upper arch (25%), midline diastema (18%), and Class III malocclusion (11%). CONCLUSION: In the present study population, the teeth were frequently affected by pulp calcification and/or deviation of the root morphology. Blunting and shortening of root(s) were more often seen in premolars than in other tooth types. Class III malocclusion was relatively prevalent. It is important to pay attention to dental anomalies and occlusion in order to provide adequate care for patients with PHP.

Craniofacial and dental characteristics of patients with vitamin-D-dependent rickets type 1A compared to controls and patients with X-linked hypophosphatemia.

ᅟOBJECTIVES: Vitamin-D-dependent rickets type 1A (VDDR1A) is a rare inherited disease caused by defective activation of vitamin D. The aim of the study was to describe the craniofacial characteristics and the dental phenotype of patients with genetically confirmed VDDR1A. The VDDR1A findings were compared to findings in patients with X-linked hypophosphatemia (XLH) and healthy controls. MATERIAL AND METHODS: Ten patients with VDDR1A were identified. The reference group for the comparison of cephalometric findings was 49 adults without chronic disease. The reference group for the comparison of dental findings was 30 adults with XLH. Clinical examination, clinical photos, and radiographs were obtained. Cephalometric analysis was performed. Photos and radiographs were visually evaluated. RESULTS: The depth of the posterior cranial fossa (d-p and d-s-iop) in VDDR1A adults was reduced compared to the reference group (p < 0.05). Five (83%) of six adults with VDDR1A and one (4%) of 25 adults with XLH had enamel hypoplasia on several incisors and/or canines (p < 0.001). Three (75%) of four adults with VDDR1A and none of 16 adults with XLH had several first molars with enamel hypoplasia (p = 0.004). Five of 7 (71%) adults with VDDR1A and 24 of 30 (80%) adults with XLH had endodontically affected teeth. CONCLUSIONS: The dental aberration of VDDR1A is more in line with the dental aberration of nutritional rickets than with the dental aberrations in XLH, suggesting the combination of low availability of both calcium and phosphate to be critical in periods of enamel formation. CLINICAL RELEVANCE: Knowledge on craniofacial and dental aberration in patients with rare diseases, e.g., inherited rickets, is of importance to the dental practitioner, especially during diagnostics and treatment in special care units.

The dental perspective on osteogenesis imperfecta in a Danish adult population.

BACKGROUND: To report on dental characteristics and treatment load in Danish adult patients with osteogenesis imperfecta (OI). METHODS: Oral examination of 73 patients with OI was performed and OI type I, III, and IV were represented by 75.3%, 8.2%, and 16.4%, respectively. Patients were diagnosed as having dentinogenesis imperfecta (DI) if they had clinical and radiological signs of DI. In the data analysis, mild OI (type I) was compared to moderate-severe OI (type III and IV). RESULTS: Discoloration of teeth was prevalent in patients with moderate-severe compared to mild OI (83.3% vs. 5.5%, p < 0.001). Cervical constriction and pulpal obliteration were frequent findings in patients with moderate-severe OI (61.1% and 88.9%, respectively), whereas pulp stones and taurodontism were diagnosed in patients with mild OI only (29.1% and 9.1%, respectively). DI was found in 24.7% of OI patients and considerably more frequent in patients with moderate-severe (94.4%) compared to mild OI (1.8%) (p < 0.001). The number of teeth with artificial crowns was significantly higher in patients with moderate-severe OI than in patients with mild OI (median 1.5, range 0-23 vs. median 0, range 0-14) (p < 0.001). The number of teeth with fillings in patients with mild OI was significantly higher than in patients with moderate-severe OI (mean 9.7, SD 5.1, median 9.0, range 1-21 vs. mean 5.0, SD 4.4, median 4.0, range 0-16) (p < 0.001). CONCLUSIONS: One fourth of patients with OI had DI, and the vast majority of them had moderate-severe OI. Whereas discoloration of teeth, cervical constriction and pulp obliteration were frequent findings in patients with moderate-severe OI, pulp stones and taurodontism were found in patients with mild OI only. In patients with moderate-severe OI, the dental treatment load was dominated by prosthetic treatment, whereas restorative treatment with fillings was more prevalent in patients with mild OI.

Prevalence and impact of infant oral mutilation on dental occlusion and oral health-related quality of life among Kenyan adolescents from Maasai Mara.

BACKGROUND: Infant Oral Mutilation (IOM) includes germectomy and early extraction of primary and permanent incisors and canines, primarily in the lower jaw. The aim of the present study was to examine the prevalence and impact of IOM, involving the removal of mandibular permanent incisors and/or canines, on dental occlusion and Oral Health-Related Quality of Life (OHRQoL) among Kenyan adolescents from Maasai Mara. METHODS: In a cross-sectional study, 284 adolescents (14-18 yrs. of age) participated in an oral examination and an interview, using a structured questionnaire on age, gender, medical history, and IOM practice. For the analysis of the dental occlusion, participants with IOM, in terms of absence of two or more permanent teeth in the mandibular incisor and/or canine tooth segments (IOM group), were compared to participants who had all six incisors and canines present in the oral cavity (control group). OHRQoL was assessed using child perception questionnaire (CPQ11-14). RESULTS: The majority of the participants (61%) had been exposed to IOM, among whom 164 (95%) had absence of two mandibular central incisors. More individuals in the IOM group had maxillary overjet exceeding 5 mm than in the control group (50.9% vs. 20%, p <  0.001). Nineteen (11%) subjects in the IOM group had mesial occlusion in contrast to none in the control group (p <  0.001). The mean and median total CPQ scores and the mean and median CPQ domain scores were low in both groups with no significant differences between the groups. CONCLUSIONS: Approximately two-thirds of the study population presented with IOM, with the majority of them missing two mandibular permanent central incisors. Although some participants with IOM had substantial maxillary overjet and mesial occlusion, only few of them showed substantial effect on their OHRQoL.

Nance-Horan syndrome-The oral perspective on a rare disease.

The present study describes seven patients with Nance-Horan syndrome, all referred to a specialized oral care unit in the Central Denmark Region. A literature search on "Nance Horan Syndrome" resulted in 53 publications among which 29 reported on dental findings. Findings reported in these papers have been systematized to obtain an overview of the reported findings and the terminology on dental morphology. All seven patients included in the present study showed deviations of crown morphology on incisors and/or molars. The only consistent and very clear dental aberration was alterations in the tooth morphology that is screwdriver-shaped incisors and bud molars being most pronounced in the permanent dentition, but were also present in the primary dentition. In addition, three patients had supernumerary teeth, and three had dental agenesis. In conclusion, a dental examination as a part of the diagnostic process may reveal distinct characteristics of the dental morphology, which could be of diagnostic value and facilitate an early diagnosis. In the description of molar morphology in NHS patients, it is recommended to use the term "bud molar." The combination of congenital cataract, screwdriwer-shaped incisors and bud-shaped molars is a strong clinical indication of Nance-Horan syndrome. © 2016 Wiley Periodicals, Inc.

Odonto-onycho-dermal dysplasia in a patient homozygous for a WNT10A nonsense mutation and mild manifestations of ectodermal dysplasia in carriers of the mutation.

BACKGROUND: Odonto-onycho-dermal dysplasia (OODD) is a rare form of ectodermal dysplasia characterized by severe oligodontia, onychodysplasia, palmoplantar hyperkeratosis, dry skin, hypotrichosis, and hyperhidrosis of the palms and soles. The ectodermal dysplasias resulting from biallelic mutations in the WNT10A gene result in highly variable phenotypes, ranging from isolated tooth agenesis to OODD and Schöpf-Schulz-Passarge syndrome (SSPS). CASE PRESENTATION: We identified a female patient, with consanguineous parents, who was clinically diagnosed with OODD. Genetic testing showed that she was homozygous for a previously reported pathogenic mutation in the WNT10A gene, c.321C > A, p.Cys107*. The skin and nail abnormalities were for many years interpreted as psoriasis and treated accordingly. A thorough clinical examination revealed hypotrichosis and hyperhidrosis of the soles and dental examination revealed agenesis of permanent teeth except the two maxillary central incisors. Skin biopsies from the hyperkeratotic palms and soles showed the characteristic changes of eccrine syringofibroadenomatosis, which has been described in patients with ectodermal dysplasias. Together with a family history of tooth anomalies, this lead to the clinical suspicion of a hereditary ectodermal dysplasia. CONCLUSION: This case illustrates the challenges of diagnosing ectodermal dysplasia like OODD and highlights the relevance of interdisciplinary cooperation in the diagnosis of rare conditions.

Upper spine morphology in hypophosphatemic rickets and healthy controls: a radiographic study.

BACKGROUND/OBJECTIVES: The aim of this study was to describe upper spine morphology in adult patients with hypophosphatemic rickets (HR) compared with controls to assess differences in spine morphology in terms of severity of skeletal impact and to study associations between spine morphology and craniofacial morphology. MATERIAL/METHODS: The study population comprised 36 HR patients and 49 controls. The atlas and axis dimensions were measured on cephalograms, and the differences between the groups were estimated by regression analysis. The upper spine morphology was visually assessed to estimate the prevalence of cervical vertebral anomalies. RESULTS: The dimensions of the atlas and the axis were larger in HR patients than in controls (P ≤ 0.001), and fusions (FUS) occurred more often in HR patients (39%) than in controls (6%; P ≤ 0.001). In HR patients, the length of the atlas correlated positively (P = 0.008) and the height of the dens correlated negatively (P = 0.043) with the severity of skeletal impact. The height of the posterior arch of the atlas and the length of the axis correlated negatively with the cranial base angle (P ≤ 0.017), and the vertical dimensions of the atlas correlated positively with the thickness of the occipital skull (P ≤ 0.015). The length of the atlas correlated positively with mandibular prognathism (P = 0.042). FUS correlated positively with the frontal and parietal thickness (P = 0.034 and P = 0.003, respectively). CONCLUSIONS: The dimension of the atlas and the axis and the prevalence of the FUS were increased in HR patients compared with controls. Upper spine dimensions were associated with craniofacial dimensions, primarily in relation to the posterior cranial fossa.

Clinical presentation and genetics of tricho-rhino-phalangeal syndrome (TRPS) type 1: A single-center case series of 15 patients and seven novel TRPS1 variants.

Tricho-rhino-phalangeal syndrome (TRPS) is a rare malformation syndrome characterized by distinctive facial, ectodermal, and skeletal features. TRPS is divided into TRPS type I/III caused by pathogenic variants in TRPS1 and TRPS type II caused by contiguous gene deletions also spanning EXT1 and RAD21. Due to its rarity, knowledge of the clinical course of TRPS remains limited. Therefore, we collected and characterized a case series of 15 TRPS type I patients (median age at diagnosis 15 [interquartile range: 10-18] years, 11 females [73%]) seen at Aarhus University Hospital, Denmark, with a median follow-up period of 10 years. We estimated a minimum point prevalence of 0.5 in 100,000 (95% CI: 0.3-0.8 per 100,000) persons. Common craniofacial features included fine and sparse hair with a high anterior hairline, eyebrows with lateral thinning and a thicker medial part, prominent ears, a bulbous nose tip with small nasal alae, a low-hanging, and often wide columella, and a long philtrum with a thin upper vermillion. Specific skeletal features included short stature and deviating and short fingers with cone-shaped epiphyses and shortened metacarpals on radiographs. The most significant morbidity of the cohort was joint complaints, which were reported by all patients, often already before the TRPS diagnosis was established. We identified ten different TRPS1 variants including both frameshift/nonsense, missense, and splice-site variants, including seven variants not previously reported in the literature. In accordance with previous literature, no genotype-phenotype correlation was identified. The clinical trajectories were heterogeneous involving pediatrics, dermatology, orthopedic surgery, clinical genetics, and/or odontology, emphasizing that close multidisciplinary collaboration is essential for early diagnosis of TRPS and to ensure proper and timely patient care and counseling.

Prevalence and Patient Characteristics of Ectodermal Dysplasias in Denmark.

Importance: Ectodermal dysplasias constitute a group of rare genetic disorders of the skin and skin appendages with hypodontia, hypotrichosis, and hypohidrosis as cardinal features. There is a lack of population-based research into the epidemiology of ectodermal dysplasias. Objective: To establish a validated population-based cohort of patients with ectodermal dysplasia in Denmark and to assess the disease prevalence and patient characteristics. Design, Setting, and Participants: This nationwide cohort study used individual-level registry data recorded across the Danish universal health care system to identify patients with ectodermal dysplasias from January 1, 1995, to August 25, 2021. A 3-level search of the Danish National Patient Registry and the Danish National Child Odontology Registry was conducted to identify patients with diagnosis codes indicative of ectodermal dysplasias; patients registered in the Danish RAREDIS Database, the Danish Database of Genodermatoses, and local databases were also added. The search results underwent diagnosis validation and review of clinical data using medical records. Of 844 patient records suggestive of ectodermal dysplasias, 791 patients (93.7%) had medical records available for review. Positive predictive values of the diagnosis coding were computed, birth prevalence was estimated, and patient characteristics were identified. Data analysis was performed from May 4 to December 22, 2023. Results: The identified and validated study cohort included 396 patients (median [IQR] age at diagnosis, 13 [4-30] years, 246 females [62.1%]), of whom 319 had confirmed ectodermal dysplasias and 77 were likely cases. The combined positive predictive value (PPV) for ectodermal dysplasia-specific diagnosis codes was 67.0% (95% CI, 62.7%-71.0%). From 1995 to 2011, the estimated minimum birth prevalence per 100 000 live births was 14.5 (95% CI, 12.2-16.7) for all ectodermal dysplasias and 2.8 (95% CI, 1.8-3.8) for X-linked hypohidrotic ectodermal dysplasias. A molecular genetic diagnosis was available for 241 patients (61%), including EDA (n = 100), IKBKG (n = 55), WNT10A (n = 21), TRPS1 (n = 18), EDAR (n = 10), P63 (n = 9), GJB6 (n = 9), PORCN (n = 7), and other rare genetic variants. Conclusions and Relevance: The findings of this nationwide cohort study indicate that the prevalence of ectodermal dysplasias was lower than previously reported. Furthermore, PPVs of the search algorithms emphasized the importance of diagnosis validation. The establishment of a large nationwide cohort of patients with ectodermal dysplasias, including detailed clinical and molecular data, is a unique resource for future research in ectodermal dysplasias.

A pilot study comparing optical coherence tomography, radiography, clinical photography, and polarisation microscopy for studies of hypomineralisation disturbances in enamel.

Aim: To investigate the use of optical coherence tomography (OCT) as a tool to assess general and localised hypomineralisation defects in the enamel. Design and Materials: Ten extracted permanent teeth (four teeth with localised hypomineralisation, four teeth with general hypomineralisation, and two healthy controls) were used in this study. In addition, four participants who underwent OCT served as living controls for the extracted teeth. Methods: The OCT results were compared with clinical photographs, digital radiographs, and polarising microscopy images of tooth sections (considered the gold standard) to determine the method with the most accurate information regarding the extent of enamel disturbances: 1) visibility of enamel disturbance (visible yes/no); if yes, 2) extent of the disturbance in the enamel; and 3) determination of the plausible involvement of the underlying dentin. Results: OCT was more accurate than digital radiography and visual assessment. OCT could provide information about the extent of localised hypomineralised disturbances in the enamel that was comparable to that with polarisation microscopy of the tooth sections. Conclusion: Within the limitations of this pilot study, it can be concluded that OCT is suitable for investigating and evaluating localised hypomineralisation disturbances; however, it is less useful in cases with generalised hypomineralisation of the enamel. In addition, OCT complements radiographic examination of enamel; however, more studies are necessary to elucidate the full extent of the use of OCT in case of hypomineralisation.

Familial colorectal cancer and tooth agenesis caused by an AXIN2 variant: how do we detect families with rare cancer predisposition syndromes?

We present a three-generation family with an AXIN2 variant and a family history of colorectal cancer (CRC), colon polyps and tooth agenesis. A likely pathogenic variant was detected in the AXIN2 gene (c.1994dup; p.(Asn666Glnfs*41)). This variant has previously been associated with tooth agenesis and polyposis, only. In this case report we describe eight carriers with tooth agenesis and variable clinical findings, including polyps and CRC. Our case provides additional knowledge to the sparse data on genotype-phenotype association related to AXIN2 associated cancer syndrome. Further, our case highlights the importance of analysing an extended CRC and oligodontia/ectodermal dysplasia gene panel including AXIN2 but also raises awareness and discussion about appropriate surveillance program.

Craniofacial morphology in patients with hypophosphatemic rickets: a cephalometric study focusing on differences between bone of cartilaginous and intramembranous origin.

Hypophosphatemic rickets (HR) are diseases characterized by deficient mineralization of bone due to abnormal renal wasting of phosphate. Deformation of bony structures of cartilaginous origin has been described as a major characteristic in patients with HR, but little is known about the impact on bony structures of intramembranous origin. The aim of the present study was to describe the osseous morphology of the craniofacial structures in patients with HR compared to healthy controls, and to investigate the impact of different bone origin on the osseous morphology. Fifty-three patients with HR (17 males, 36 females), aged 3-74 yrs, were included. Fifty HR patients had dominant X-linked disease, and in three patients no mutations were identified. A total of 79 healthy individuals (37 males, 42 females), aged 6-79 yrs, with normal occlusion served as controls. Significant cephalometric differences were found between HR patients and controls. In HR patients, the cranial base was flattened and the depth of the posterior cranial fossa was decreased. The anterior height of the cranium, the angle nasion-sella-frontale, and the thickness of theca were increased. The length of the nasal bone and the height of the maxilla were reduced. In contrast, the vertical as well as the sagittal relation between the jaws were unaffected in HR patients compared to controls. In conclusion, we found that the cranial structures of cartilaginous origin as well as the structures of intramembraneous origin were affected in patients with HR.

Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a Danish five-generation family with a novel FAM83H nonsense mutation.

BACKGROUND. Autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI) is a disease with severe dental manifestations. OBJECTIVES. The aims were by means of a genome-wide linkage scan to search for the gene underlying the ADHCAI phenotype in a Danish five-generation family and to study the phenotypic variation of the enamel in affected family members. RESULTS. Significant linkage was found to a locus at chromosome 8q24.3 comprising the gene FAM83H identified to be responsible for ADHCAI in other families. Subsequent sequencing of FAM83H in affected family members revealed a novel nonsense mutation, p.Y302X. Limited phenotypic variation was found among affected family members with loss of translucency and discoloration of the enamel. Extensive posteruptive loss of enamel was found in all teeth of affected subjects. The tip of the cusps on the premolars and molars and a zone along the gingival margin seemed resistant to posteruptive loss of enamel. We have screened FAM83H in another five unrelated Danish patients with a phenotype of ADHCAI similar to that in the five-generation family, and identified a de novo FAM83H nonsense mutation, p.Q452X in one of these patients. CONCLUSION. We have identified a FAM83H mutation in two of six unrelated families with ADHCAI and found limited phenotypic variation of the enamel in these patients.

Prevalence of JP2 and Non-JP2 Genotypes of Aggregatibacter actinomycetemcomitans and Oral Hygiene Practice of Kenyan Adolescents in Maasai Mara.

Aggregatibacter actinomycetemcomitans is implicated in the etiology of periodontitis that affects adolescents. The monitoring and mapping of the geographic dissemination pattern of JP2 and non-JP2 genotypes of A. actinomycetemcomitans are of interest. In Africa, the highly leukotoxic JP2 genotype is known to be prevalent, particularly in north-west Africa. The aims of this study were to determine the prevalence of JP2 and non-JP2 genotypes and investigate the oral hygiene practices among adolescents living in Maasai Mara, Kenya. A total of 284 adolescents (mean age: 15.0 yrs; SD 1.1) were interviewed regarding their age, gender, medical history, and oral hygiene practice, and the number of teeth present was recorded. One subgingival pooled plaque sample from all the first molars of each participant was analyzed by conventional PCR. The mean number of permanent teeth present was 27.9 (SD: 2.0; range: 22-32; 95% CI: 27.7-28.1). Sixteen (5.6%) and two (0.7%) adolescents were positive for non-JP2 and JP2 genotypes, respectively. For the vast majority of the adolescents, the use of a toothbrush (99.3%) and toothpaste (80.1%), as well as some kind of toothpick (>60.2%), were part of their oral hygiene practice, with dental floss (0.4%) and/or mouth rinses (0.4%) rarely being used. We have, for the first time, identified Kenyan adolescents colonized with the JP2 genotype. The prevalence of the JP2 genotype of A. actinomycetemcomitans is low, a possible indicator that it spreading through human migration from North and West Africa to East Africa is a rare occasion.