Jan Huggare

Mapping of the second locus for the Van der Woude syndrome to chromosome 1p34

The Van der Woude syndrome (VWS) is a dominantly inherited developmental disorder characterized by pits and/or sinuses of the lower lip, cleft lip and/or cleft palate. It is the most common cleft syndrome. VWS has shown remarkable genetic homogeneity in all populations, and so far, all families reported have been linked to 1q32-q41. A large Finnish pedigree with VWS was recently found to be unlinked to 1q32-q41. In order to map the disease locus in this family, a genome wide linkage scan was performed. A maximum lod score of 3.18 was obtained with the marker D1S2797, thus assigning the disease locus to chromosomal region 1p34. By analyses of meiotic recombinants an ∼30 cM region of shared haplotypes was identified. The results confirm the heterogeneity of the VWS syndrome, and they place the second disease locus in 1p34. This finding has a special interest because the phenotype in VWS closely resembles the phenotype in non-syndromic forms of cleft lip and palate.

Postural disorders and dentofacial morphology.

Although the history of opinions regarding poor posture as an etiologic factor for deviant dentofacial development and malocclusions is old, very few controlled studies on this topic have been done. Most of the articles are anecdotal or describe subjective clinical impressions. Some studies do present valid material, but unfortunately they often do not provide enough information about the methods for postural recording. Based on selected studies, this review concludes that there is plausible evidence for an increased prevalence of Angle Class II malocclusions associated with hyperlordosis of the cervical spine and an increased risk of lateral crossbite in children affected by scoliosis and torticollis. Also, documentation of associations between anterior crowding and head posture seem convincing.

Orthodontic Study Cast Analysis—Reproducibility of Recordings and Agreement Between Conventional and 3D Virtual Measurements

Digital imaging of dental casts has become an alternative to conventional cast analysis in orthodontic treatment planning. The reproducibility of angular measurements made on virtual digital models has not as yet been evaluated. In order to study reproducibility for and agreement between a conventional analysis technique and virtual 3D imaging, 20 dental casts from subjects in the early mixed dentition, were measured twice with each technique by two orthodontists. Variables of interest were incisor rotation, angulation and irregularity, arch width, arch circumference, overjet, and overbite. Standard deviation (Dahlberg 1940) and coefficient of variation were used for evaluation of reproducibility. Mean differences between methods and examiners, correlation between mean differences and mean levels and 95% limits of agreement were used for describing systematic errors. The conventional technique showed less intraexaminer variation for angular variables than the 3D imaging method. Linear variables, with the exception of overbite, showed no clear trend as regards differences in reproducibility between the two methods. In general, examiner 1 showed less intraexaminer variation than examiner 2. The mean differences between the two methods expressed higher values for assessment of rotations with the O3DM method. Both angular and linear variables exhibited poor 95% limits of agreement. The conventional technique showed better overall reproducibility and thus appears to be more suitable for scientific work. However, the reproducibility attained by O3DM is clearly acceptable for clinical use. The two methods should not be used interchangeably.

Head posture and dentofacial asymmetries in surgically treated muscular torticollis patients.

Muscular torticollis is a medically well-known condition that is usually diagnosed in early childhood and in which early surgical intervention is recommended to prevent the development of facial asymmetries. The purpose of this study is to examine head posture and possible dentofacial asymmetries in patients who have undergone surgical treatment for muscular torticollis in early childhood. Natural head position roentgenograms were taken in frontal projection, a clinical examination of oral status was performed, and dental casts were made. Marked craniofacial and dental asymmetries were observed, combined with a deviant head posture, in spite of surgical treatment for muscular torticollis earlier in childhood.

Maximal bite force and its associations with spinal posture and craniofacial morphology in young adults

Maximal bite force (MBF) and its associations with craniofacial morphology and spinal posture were studied in a group of young adults (46 M and 38 F) aged 21 to 23 years. MBF was recorded in molar and incisal regions. Sagittal spinal posture was measured by spinal pantography and trunk asymmetry at thoracic and lumbar levels by a forward-bending test. Craniofacial variables and posture of the cervical spine were examined from lateral cephalograms taken in a natural head position. No statistically significant correlations existed between MBF and spinal posture, but significant correlations did exist between MBF and craniofacial variables, especially in women.

Craniofacial morphology in obese adolescents

Overweight and obesity are growing problems in the world today. A recent survey shows that about 30% of the adolescent and adult Swedish population is overweight or obese. The etiology is a combination of many factors, the most important of which are physical inactivity and high caloric diet. Obese children have a normal to accelerated growth rate despite low growth hormone (GH) levels. The aim of our study was to investigate whether craniofacial morphology differs between obese adolescents and normal weight adolescents. Lateral cephalograms from 39 adolescents with obesity, aged 14-16 years, were analysed and compared with lateral cephalograms from an equal number of sex- and aged-matched controls. Compared to the controls, the subjects in the obesity group showed increased mandibular length, prognathic jaws and a reduced upper anterior face height. Despite low GH levels, obese children have normal levels of insulin-like growth factor (IGF-1). Since we found an advanced craniofacial growth in obese adolescents with low GH and high IGF-1 serum levels, craniofacial growth may be more dependent on free circulating IGF-1 than on the locally produced portion.

Linkage Analysis of Candidate Regions in Swedish Nonsyndromic Cleft Lip with or without Cleft Palate Families

OBJECTIVE To analyze linkage of five candidate regions for nonsyndromic cleft lip with or without palate (CLP) on chromosome 2p13, 4q, 6p23, and 19q13; in addition chromosome 1q32, the locus for van der Woude syndrome, on Swedish CLP families. DESIGN Three to five linked microsatellite markers were selected from each candidate region. Polymerase chain reaction (PCR) with fluorescent-labeled microsatellite markers was performed on DNA samples from the participating families. Electrophoresis of the PCR products was performed on a laser-fluorescent DNA sequencer. The genotype data were analyzed with multipoint linkage analysis. Modes of inheritance tested included two autosomal dominant, an autosomal recessive, and a nonparametric model. Multipoint logarithm of odds (LOD) scores were also calculated by assuming genetic heterogeneity. PARTICIPANTS Nineteen Swedish multigenerational families with at least two first-degree relatives affected with CLP. Greater than 50% of the families studied show vertical transmission of the clefting phenotype and both inter- and intrafamilial variability were noted. RESULTS Cumulative multipoint LOD scores for the whole group of families calculated under autosomal dominant modes of inheritance were negative in all regions and less than -2 except chromosome 6p23. LOD scores calculated under recessive inheritance and the nonparametric model were inconclusive. There was no significant evidence of genetic heterogeneity among the sample group. CONCLUSIONS The group of Swedish CLP families did not demonstrate significant linkage to any of the five candidate regions examined. This might suggest a new but yet unknown CLP locus or loci in this family group. However, because linkage could not be excluded in some individual families, they should still be tested with candidate genes from these regions.

Associations between thoracic kyphosis, head posture, and craniofacial morphology in young adults

The aim of the present study was to investigate associations between thoracic hyper- and hypokyphosis, head posture, and craniofacial morphology in young adults. Using forward bending test and spinal pantographic measurements, 31 subjects, 16 with thoracic hyper- and 15 with hypokyphosis, were selected from a population-based cohort of 430 young adults. Lateral roentgen-cephalograms were taken in natural head posture and craniofacial and postural angular measurements were calculated. Any statistically significant differences between the groups - thoracic hyperkyphosis and thoracic hypokyphosis - were analysed using Students t test. Subjects with thoracic hyperkyphosis had a larger atlantocervical angle (At/CVT, P < 0.01) than subjects with thoracic hypokyphosis. However, head position (NSL/VER)was similar in both groups, probably owing to the visual perception control of craniovertical relation. There was no statistically significant difference in craniofacial morphology between the groups.

Clinical and genetic studies of Van der Woude syndrome in Sweden.

Van der Woude syndrome (VWS) is an autosomal dominant craniofacial disorder characterized by pits of the lower lip, hypodontia and cleft lip and/or cleft palate. It has been reported as the most common form of syndromic orofacial clefting with very high penetrance and varied expressivity. The disease locus for VWS has been mapped to chomosome 1q32, but the gene is yet to be cloned. Here we report a total of 11 Swedish VWS patients: 9 familial cases from two families and two isolated cases. Clinical examination of these patients showed phenotypic variability, even between patients from the same family. Genetic studies were performed using four microsatellite markers from chromosome 1q32. Constitutional deletion in this region was not demonstrated in any of the familial or isolated cases. However, in the two VWS families, linkage analysis using these markers showed positive LOD (logarithm of the odds) scores ranging from 2.56 to 2.88 to all individual markers. The highest LOD score of 3.75 was obtained with the combined haplotypes of D1S491 and D1S205, thus confirming linkage of VWS in these two families to 1q32. We conclude that there is varied expressivity but no evidence of genetic heterogeneity in VWS.

A modification of the pressure-flow technique for measuring breathing of cold air and its effect on nasal cross-sectional area

The purpose of this article was to develop a method based on the pressure-flow technique for measuring cold air breathing and to observe the immediate reactions of breathing function to cold air inhalation in 40 subjectively healthy adults. The pressure-flow technique was used to measure airflow rate and oral/nasal pressure and to calculate the smallest cross-sectional area of the nasal airway. The equipment was modified to allow measurements both at room temperature and with cooled air by connecting the nasal mask to a freezer with a two-valve cylinder and tubing. Nasal cross-sectional area showed a significant decrease from 42.3 mm2 at room temperature to 37.6 mm2 with cooled air. Correspondingly, the airflow rate changed from 411 ml/s to 369 ml/s, whereas the differential pressure remained about the same, 1.2 and 1.3 cm H2O, respectively. The interindividual variation was fairly large. The results suggest that the breathing of cold air seems to cause changes in nasal cross-sectional area and airflow rate. In general, the cross-sectional area diminishes, the change being quantitatively more pronounced in subjects with an initially large area.