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The major diagnostic manifestations in Sotos syndrome include frontal bossing, downward slanting palpebral fissures, a prominent jaw, learning disability, and childhood overgrowth. Over 90% of clinically diagnosed patients have an abnormality in the NSD1 gene. We investigated the dental manifestations of this disorder and found one or several premolar teeth were absent in 9 out of 13 (69%) affected children and adolescents. A heterozygous mutation in the NSD1 gene was identified in 12 patients, including all patients with hypodontia. The severity of the hypodontia seemed to increase with the severity of aberration of the NSD1. More than 50% of the patients had enamel defects or excessive tooth wear. Dental age, based on tooth formation, was within the normal range. A characteristic occlusion for Sotos syndrome could not be identified. As agenesis of premolars was a common feature in these patients affected with Sotos syndrome, we recommend panoramic radiography at the age of 7 years. If premolars are missing, proper preventive and restorative care is necessary to maintain the deciduous molars. © 2009 Wiley-Liss, Inc.

Cohen syndrome (Mendelian Inheritance in Man [MIM] no. 216550) is a rare, autosomal-recessive inherited disorder with mental retardation and a typical appearance. The condition is relatively common in Finland where 35 patients have been diagnosed. We studied 22 patients in detail, obtaining anthropometric measurements of the head and face, and cephalometric radiographs of 14 patients (14-57 years of age). Measurements of patients were compared to population norms and matched controls. Anthropometric analysis confirmed and quantified the previously described syndrome features: small head size [-4 standard deviations (SD)], with varying cephalic index. Width of the upper face was close to normal, but width of the lower face was small. Philtrum length was shorter than in healthy controls (p = 0.0039 in females and p = 0.0014 in males). The measurements from standardized radiographs revealed short cranial base dimensions (-2.2 and -2.6 SD), but normal cranial base angles. Prognathism of jaws was within normal limits. Reduced head size (microcephaly), short philtrum and small cranial base dimensions are essential features in Cohen syndrome. In addition, most patients had forward-inclined upper incisors and maxillary prognathia. We conclude that exact measurements mostly confirmed the Cohen syndrome description based previously on clinical impression.

Short-root anomaly (SRA), occurring mostly in maxillary incisors, is defined as developmentally very short, blunt dental roots. The condition has a genetic background and is related to hypodontia. Earlier population studies have been based on schoolchildren with developing dentitions and have indicated prevalence figures between 1% and 10%. We studied a random sample of existing panoramic radiographs of 2000 university students for SRA. Roots as long as or shorter than the crowns in the incisors and visually evaluated as very short, blunt roots bilaterally in the posterior teeth were classified as SRA. The prevalence was 1.3%. According to anamnestic information, half the SRA patients had undergone orthodontic therapy, but pre-treatment radiographs were unavailable. In 70% of the SRA patients the short-rooted tooth pairs were upper incisors, but also involved were maxillary premolars, lateral incisors, and lower second premolars. Women were significantly more often affected. We discuss other factors known to cause short-rooted teeth and conclude that the population prevalence for genetic SRA in fully developed dentitions is close to our 1.3%.

We determined differences in the expression of certain virulence factors between oral Candida dubliniensis and Candida albicans species. In addition, clonal differences were sought among C. albicans isolates recovered from patients with and without compromised immune system. The material comprised 93 clinical yeast isolates originated in 40 subjects (1-5 isolates per subject). All 26 C. dubliniensis isolates and 46 C. albicans isolates originated from healthy routine dental clinic patients. Additionally, 21 C. albicans isolates were collected from patients with autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy (APECED), who have chronic candidosis as one manifestation of their immunocompromising disease. Polymerase chain reaction amplification using the random sequence primer OPE-03 enabled grouping of the C. dubliniensis isolates in 2 genotypes (I and II) and C. albicans isolates in 15 genotypes (I-XV). No significant difference was found in the distribution of genotypes between the patients with APECED and the healthy subjects. C. dubliniensis isolates exhibited high-frequency phenotypic switching significantly more frequently than did C. albicans isolates, and vice versa regarding phospholipase and proteinase production. Proteinase production was significantly more frequent among C. albicans genotype V than genotype IX isolates. No significant difference was found in expression of virulence factors of C. albicans isolates between the patients with APECED and the healthy subjects.

Cleidocranial dysplasia (CCD) is a dominantly inherited skeletal dysplasia caused by mutations in the osteoblast-specific transcription factor CBFA1. To correlate CBFA1 mutations in different functional domains with the CCD clinical spectrum, we studied 26 independent cases of CCD and a total of 16 new mutations were identified in 17 families. The majority of mutations were de novo missense mutations that affected conserved residues in the runt domain and completely abolished both DNA binding and transactivation of a reporter gene. These, and mutations which result in premature termination in the runt domain, produced a classic CCD phenotype by abolishing transactivation of the mutant protein with consequent haploinsufficiency. We further identified three putative hypomorphic mutations (R391X, T200A and 90insC) which result in a clinical spectrum including classic and mild CCD, as well as an isolated dental phenotype characterized by delayed eruption of permanent teeth. Functional studies show that two of the three mutations were hypomorphic in nature and two were associated with significant intrafamilial variable expressivity, including isolated dental anomalies without the skeletal features of CCD. Together these data show that variable loss of function due to alterations in the runt and PST domains of CBFA1 may give rise to clinical variability, including classic CCD, mild CCD and isolated primary dental anomalies.

The effects of cervical inclination and body position on airway measurements were studied in 12 cadavers (8 males) aged 26–62 years. None had any injuries in the head and neck region or anomalies of the cervical spine. The upper airway of the tracheostomized cadavers was cleaned by suction and radiopaque contrast media was sprayed into the pharynx. Lateral cephalometric X-rays were taken in a modified cephalostat. In order to obtain maximum cervical flexion and extension as well as a middle position, the cephalostat was adjusted in antero–posterior dimension for three cervical inclinations in both upright and supine positions. When taking the radiographs the Frankfort plane was adjusted so that it was horizontal when the subject was seated and vertical while the subject was recumbent. Cephalometric pharyngeal airway dimensions were measured at five levels ranging from palatopharynx to hypopharynx. We found that pharyngeal airway dimensions increased at all levels with increasing cervical inclination, while supine posture independently decreased the measurements. The effect of cervical inclination was larger at lower levels of pharynx than at higher levels. These findings indicate that cervical inclination plays a major role in modifying the dimensions of the passive upper airway. Therefore the effects of cervical inclination and body position should be adjusted for in studies of the upper airway in cadavers, and probably also in anesthetized subjects.

In the present study, we collected a family series with short root anomaly in order to analyze the inheritance pattern of the condition. Another aim was to identify in these families an association with other dental anomalies, such as tooth agenesis, peg-shaped lateral incisors, supernumeraries, ectopia, and such morphological characteristics as invaginations, taurodontism, and a tendency to root resorption. Mesiodistal dimensions of the crowns of the affected teeth were measured in order to reveal any association with reduction or increase in tooth size. The apparent genetic heterogeneity of the pedigrees did not permit definitive conclusions as to the mode of inheritance. Autosomal dominant transmission of short root anomaly was seen in 3/8 families. In 2/8 families, the condition was seen in siblings but not in parents. An association with tooth agenesis and ectopic canines was noted, the prevalences of which were 46% and 33%, respectively. We stress the importance of not misdiagnosing this anomaly as resorption.

The aim of this study was to assess the oral health of patients with aspartylglucosaminuria, a heritable lysosomal storage disorder, and to recommend guidelines for treatment.Eighty-two patients with aspartylglucosaminuria and 122 control subjects were examined clinically; in addition, panoramic radiographs were evaluated in 61 patients with aspartylglucosaminuria and 61 control subjects.High prevalences of caries, gingivitis, and oral Candida (P.001), extensive gingival overgrowths (18%; P.001), benign odontogenic tumors or tumorlike lesions (8%; P = .057), reduced maxillary sinuses (P.001), limited mouth opening (P.001), and food retention in the mouth (45%) were the major oral findings that distinguished the patients with aspartylglucosaminuria from the control subjects. Adults with aspartylglucosaminuria had diverse oral health problems, early loss of several permanent teeth being the most disabling feature.Patients with aspartylglucosaminuria appear to be at a higher risk for a number of oral disorders; however, poor oral hygiene and failure to cooperate increase these patients' risk of dental and periodontal diseases, making successful prevention crucial.

Skeletal stability during the first year after mandibular advancement surgery and fixation using biodegradable self-reinforced poly-l-lactide (SR-PLLA) screws, without postoperative intermaxillary fixation, was studied in 25 patients by means of cephalometric measurements. The magnitude of advancement was on average, 3.88 mm at pogonion (PG) (range 1.25-6.5 mm) and 4.57 mm at B-point (range 2.75-7.5 mm). After one year a mean relapse backwards of 0.59 mm at the PG (15%) and 0.78 mm at the B-point (17%) was observed. Nineteen patients (76%) and 17 patients (68%) were stable at PG and B-point, respectively. SR-PLLA screws are considered to be comparable to other forms of rigid internal fixation for fixation of bilateral splitting osteotomies after mandibular advancement, as far as skeletal stability is concerned.

Objective – To show that the head may shrink in adult patients with aspartylglucosaminuria (AGU), a neurodegenerative disease. Method – The head circumference (HC) of 40 adult patients (age at baseline 15 to 47) was measured twice with an interval of 10 years. Of these 40, 21 aged 15–47 and 19 young patients aged 5–14 as well as 40 healthy controls underwent lateral cephalometric radiography. Results – During 10 years’ follow-up, the HC of 26 (65%) had decreased by 1 to 4.5 cm (mean 1.7, P

Despite its unequivocal advantages, breast feeding may be associated with undesired side-effects. Recently, we have shown an association between exposure via mother's milk to dioxins and developmental defects of the child's teeth. The present study was undertaken to analyze further the association between the duration of breast feeding and the occurrence of dental defects. For this purpose, 2 different populations were selected. The first population comprised 40 children who had mineralization defects in the permanent 1st molars, and their age-living area- and sex-matched controls. The median duration of breast feeding was 9 months in the affected children compared to 6 months in the controls. The defects were more extensive after prolonged breast feeding. The second population consisted of 97 children whose mothers had been encouraged to extensive and prolonged breast feeding. Of these children, 24 had mineralization defects. They all had been breastfed longer than 8 months. In both study populations mineralization defects were associated with the duration of breast feeding. The result suggests that long breast feeding may increase the risk of mineralization defects in healthy children, possibly because of environmental contaminants that interfere with tooth development.

Hypodontia, congenital absence of one or a few permanent teeth without any systemic disorders, is regarded as an autosomally inherited dominant condition with varying expression and incomplete penetrance. Many studies have reported that the prevalence of hypodontia varies from 5% to 10% among European and Asian populations. The teeth most often missing are second premolars, upper lateral incisors, and lower central incisors. Consequently, we call this trait incisor-premolar hypodontia. Peg-shaped or strongly mesio-distally reduced upper lateral incisors demonstrate variation in the expression of the trait. The gene or genes causing incisor-premolar hypodontia are not known. We have begun the genetic mapping of hypodontia by using linkage analyses in seven Finnish three-generation families with 77 individuals, 31 affected with incisor-premolar hypodontia. As the first step, we studied the possibility of linkage between hypodontia and some candidate genes which have been suggested to have important functions during tooth development. Here we report the exclusion of EGF, EGFR, and FGF-3 loci as possible sites for gene mutation causing incisor-premolar hypodontia in our family material. Because of the close location of the FGF-3 and FGF-4 genes, the results also suggest the exclusion of the FGF-4 locus.

Failure to develop complete dentition, tooth agenesis, is a common developmental anomaly manifested most often as isolated but also as associated with many developmental syndromes. It typically affects third molars or one or few other permanent teeth but severe agenesis is also relatively prevalent. Here we report mutational analyses of seven candidate genes in a cohort of 127 probands with non-syndromic tooth agenesis. 82 lacked more than five permanent teeth excluding third molars, called as oligodontia. We identified 28 mutations, 17 of which were novel. Together with our previous reports, we have identified two mutations in MSX1, AXIN2 and EDARADD, five in PAX9, four in EDA and EDAR, and nine in WNT10A. They were observed in 58 probands (44%), with a mean number of missing teeth of 11.7 (range 4 to 34). Almost all of these probands had severe agenesis. Only few of the probands but several relatives with heterozygous genotypes of WNT10A or EDAR conformed to the common type of non-syndromic tooth agenesis, incisor-premolar hypodontia. Mutations in MSX1 and PAX9 affected predominantly posterior teeth, whereas both deciduous and permanent incisors were especially sensitive to mutations in EDA and EDAR. Many mutations in EDAR, EDARADD and WNT10A were present in several families. Biallelic or heterozygous genotypes of WNT10A were observed in 32 and hemizygous or heterozygous genotypes of EDA, EDAR or EDARADD in 22 probands. An EDARADD variant were in seven probands present together with variants in EDAR or WNT10A, suggesting combined phenotypic effects of alleles in distinct genes.

The aims of the present study were to provide data on growth changes in the dental arches from age 7 to 32 in Finns with untreated normal Angle Class I occlusions. The material consisted of 33 series of dental casts of 18 women and 15 men. The subjects had been examined and study models taken at the ages of 7, 10, 12, 15, and 32. Dental arch width, overbite, and overjet were measured. Our longitudinal findings show that both the dental arches of young adults are slightly narrowed from adolescence to 32 years of age. All increases in width dimensions took place before 15 years of age. The means of the changes were mostly small, in the order of 0.5 to a few millimetres. Variability in age changes was considerable. In both genders, each variable increased in some subjects and decreased in others during every age interval. Differences between growth changes in the mesial, distal, and gingival intermolar widths indicate that both the maxillary and the mandibular first molars rotate mesiolingually and that the maxillary first molars also become more upright during late occlusal development. We expect the present findings of the changes occurring in the arch dimensions of subjects with untreated normal occlusions to help clinicians in following up occlusal development, choosing an optimal treatment time, and making orthodontic treatment and retention plans. However, because of the wide variability, accurate prediction of future development cannot be made on the individual level.

Rapid infantile growth was the first clinical sign in patients (n = 51) with aspartylglycosaminuria, a lysosomal storage disorder. Even if young children with aspartylglycosaminuria were tall for their age, an early but weak pubertal growth spurt in both sexes resulted in reduced adult heights.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autosomal recessive disease exceptionally common in Finland. It is associated with a limited T lymphocyte defect, an autoimmune response to various tissues, particularly endocrine glands. Most patients have chronic oral candidosis, which has been suggested to be carcinogenic. In Finland 92 patients have been diagnosed with APECED and 66 of them are alive. Our aim was to study the possible association of APECED with oral and oesophageal carcinoma. We evaluated the medical histories of all 92 patients for morbidity, causes of death, and known risk factors for oral cancer. We invited all current patients for a clinical examination of their oral mucosa. Six of the 92 had developed oral or oesophageal squamous cell carcinoma (SCC) by the mean age of 37 (29-44years) and four of them had died from it. The six represent 10% of the patients older than 25years. Five of the six patients had long-lasting oral candidosis. Four of the six had smoked regularly for 15years or more. One patient had been on immunosuppressive therapy for 6years following kidney transplantation when SCC in her mouth occurred. The partial T cell defect of APECED seems to favour the growth of Candida albicans and predispose to chronic mucositis and SCC. Aggressive control of oral candidosis and close follow-up of oral mucosa is a necessity in patients with APECED.

Abnormalities of the short arm of chromosome 4 cause multiple congenital malformations, including craniofacial, oral, and dental manifestations. A candidate gene for oral defects in this region is MSX1, which is mandatory for normal oral and tooth development. We examined the dentition and the presence of MSX1 in eight Finnish patients with abnormalities of 4p, including seven cases of Wolf-Hirschhorn syndrome. Five of the Wolf-Hirschhorn syndrome patients presented with agenesis of several teeth, suggesting that oligodontia may be a common (even though previously not well-documented) feature in Wolf-Hirschhorn syndrome. In fluorescence in situ hybridization (FISH) analysis, the five patients with oligodontia lacked one copy of MSX1, while the other three had two hybridization signals. One of these presented with the only case of cleft palate among the patients. Our result confirms that haploinsufficiency for MSX1 serves as a mechanism that causes selective tooth agenesis but, alone, is not enough to cause oral clefts.

Mutations in PAX9 have been described for families in which inherited oligodontia characteristically involves permanent molars. Our study analysed one large family with dominantly inherited oligodontia clinically and genetically. In addition to permanent molars, some teeth were congenitally missing in the premolar, canine, and incisor regions. Measurements of tooth size revealed the reduced size of the proband's and his father's deciduous and permanent teeth. This phenotype is distinct from oligodontia phenotypes associated with mutations in PAX9. Sequencing of the PAX9 gene revealed a missense mutation in the beginning of the paired domain of the molecule, an arginine-to-tryptophan amino-acid change occurring in a position absolutely conserved in all sequenced paired box genes. A mutation of the homologous arginine of PAX6 has been shown to affect the target DNA specificity of PAX6. We suggest that a similar mechanism explains these distinct oligodontia phenotypes.

Nonsyndromic tooth agenesis is a genetically and phenotypically heterogenous condition. It is generally assumed that different phenotypic forms are caused by different mutated genes. We analyzed inheritance and phenotype of hypodontia and dental anomalies in 214 family members in three generations of 11 probands collected for genetic linkage study on incisor-premolar hypodontia (IPH). Our analysis confirms the autosomal-dominant transmission with reduced penetrance of IPH. The prevalence of hypodontia and/or peg-shaped teeth was over 40% in first-and second-degree relatives and 18% in first cousins of the probands. Four of nine noted obligate carriers of hypodontia gene had dental anomalies, including small upper lateral incisors, ectopic canines, taurodontism, and rotated premolars. These anomalies were also observed at higher than normal frequency in relatives affected with hypodontia. We conclude that incisor-premolar hypodontia is a genetic condition with autosomal-dominant transmission and that it is associated with several other dental abnormalities.

Development of dentition is controlled by numerous genes, as has been shown by experimental animal studies and mutations that have been identified by genetic studies in man. Here we report a nonsense mutation in the PAX9 gene that is associated with molar tooth agenesis in a Finnish family. The A340T transversion creates a stop codon at lysine 114, and truncates the coded PAX9 protein at the end of the DNA-binding paired-box. All the affected members of the family were heterozygous for the mutation. The tooth agenesis phenotype involves all permanent second and third molars and most of the first molars and resembles the earlier reported phenotype that was also associated with a PAX9 mutation.1 The phenotype is presumably a consequence of haploinsufficiency of PAX9. In another Finnish family with molar tooth agenesis, we could not find similar sequence changes in PAX9.

Many craniofacial and dental anomalies have a genetic background. Much research related to the molecular pathology of genetic conditions is being carried out, and new information related to mapping of disease genes, gene identification, and mutations in these genes is accumulating with incredible speed. It is important to be well informed of the molecular background of the conditions that we treat at anomaly clinics. This article reviews the most recent molecular findings related to Turner syndrome, Beckwith-Wiedemann syndrome, Marfan syndrome, Treacher Collins syndrome, cleidocranial dysplasia, and cleft lip and palate.

Holding a violin between shoulder and chin needs a special kind of muscle function. The purpose of this investigation was to determine whether this kind of muscular activity is a modifying factor for facial growth in adolescence. The bony facial dimensions of 24 adolescent violin students attending colleges of music with a playing history of 5-11 years were measured from lateral and posteroanterior cephalograms and panoramic tomograms of the jaws. The dimensions were compared with those of sex- and age-matched controls. Significant differences were found between violin players and controls. The players had higher faces, especially on the right side of the lower face and in the right mandibular ramus. The players also had more proclined upper and lower incisors than the controls. It is concluded that the overall greater facial height in violinists reflects the increased face muscle activity and the higher bony dimensions of the right side of the face are due to the muscular activity produced on that side to balance the load caused by the violin on the left. The greater proclination of the incisors is the result of an altered balance of muscular activity between tongue and lip, and the pressure of the violin to the chin.

Professional violin and viola playing involves a particular kind of asymmetric face, neck and shoulder muscle activity. The aim of this study was to find out whether players' facial morphology is influenced by this occupational orofacial muscle activity. Lateral and posteroanterior cephalograms and panoramic tomograms of 26 adult professional violin and viola players were evaluated and compared with those of age, sex and dentition matched controls. Significant differences were found between the players and the controls. The players had smaller facial heights, more proclined maxillary incisors and greater mandibular lengths. Thus, intense long-term violin/viola playing has the effect of modifying facial morphology.

The palatally displaced canine is a harmful complication of dental development. It appears in 1 to 2% of the Western population. According to our clinical experience, this anomaly is seen in families in which missing and peg-shaped teeth are common. It could be caused by the same genetic component that causes incisor-premolar hypodontia. We examined 106 patients who had been operated on and treated orthodontically for palatally impacted canine(s). The patients and their family members were examined for dental anomalies. One hundred and ten first- and 93 second-degree relatives were clinically and radiologically examined, and 35 pedigrees were constructed. Thirty-six percent of the patients had congenitally missing permanent teeth (hypodontia), which is 4.5 times the population prevalence. Hypodontia was noted in 19 to 20% of both the first- and second-degree relatives. This is 2.5 times the population prevalence. Frequency of missing teeth, analyzed by tooth groups, was of the same order as that shown for incisor-premolar hypodontia in the Western population. In six of the 35 pedigrees, a palatally impacted canine was noted in several generations of the same family. Prevalence of this anomaly was 4.9% in the studied group, which is 2.5 times the population prevalence. From the findings, we conclude that the palatally displaced canine belongs to the spectrum of dental abnormalities related to hypodontia.

This paper presents an updated review of the role of endocrine factors in craniofacial and dental development. Some unpublished results of the author's own studies are presented. Longitudinal growth studies have shown the similarity of facial and somatic growth rates, whereas dental development has been found to be independent. The increased therapeutic use of the growth hormone (GH) has focused attention on the dental and craniofacial effects of GH. Whereas delayed and advanced cranial base and facial growth is obvious in conditions with either lack or excess of GH, the effect of GH on the dentition is less clear. Thyroid hormones seem to be necessary for the eruptive movement of teeth. Sex steroids clearly have an effect on facial and cranial base growth and are also odontogenic, but the effects have not been much studied. The growth-inhibiting effect of corticosteroids is explained partly by the reduced response of cartilage cells to insulin-like growth factor-1. Experimentally, the effect is also seen in the condylar cartilage, but clinical studies have not been published. In tooth eruption an accelerating effect has been noted in experimental animals. The role of androgenic hormones in mandibular growth stimulation is discussed.