Metopic and sagittal synostosis in Greig cephalopolysyndactyly syndrome: five cases with intragenic mutations or complete deletions of GLI3

Greig cephalopolysyndactyly syndrome (GCPS) is a multiple congenital malformation characterised by limb and craniofacial anomalies, caused by heterozygous mutation or deletion of GLI3. We report four boys and a girl who were presented with trigonocephaly due to metopic synostosis, in association with pre- and post-axial polydactyly and cutaneous syndactyly of hands and feet. Two cases had additional sagittal synostosis. None had a family history of similar features. In all five children, the diagnosis of GCPS was confirmed by molecular analysis of GLI3 (two had intragenic mutations and three had complete gene deletions detected on array comparative genomic hybridisation), thus highlighting the importance of trigonocephaly or overt metopic or sagittal synostosis as a distinct presenting feature of GCPS. These observations confirm and extend a recently proposed association of intragenic GLI3 mutations with metopic synostosis; moreover, the three individuals with complete deletion of GLI3 were previously considered to have Carpenter syndrome, highlighting an important source of diagnostic confusion.

Phylogenetic and virulence analysis of tick-borne encephalitis virus field isolates from Switzerland

Tick-borne encephalitis (TBE) is an endemic disease in Switzerland, with about 110-120 reported human cases each year. Endemic areas are found throughout the country. However, the viruses circulating in Switzerland have not been characterized so far. In this study, the complete envelope (E) protein sequences and phylogenetic classification of 72 TBE viruses found in Ixodes ricinus ticks sampled at 39 foci throughout Switzerland were analyzed. All isolates belonged to the European subtype and were highly related (mean pairwise sequence identity of 97.8% at the nucleotide and 99.6% at the amino acid level of the E protein). Sixty-four isolates were characterized in vitro with respect to their plaque phenotype. More than half (57.8%) of isolates produced a mixture of plaques of different sizes, reflecting a heterogeneous population of virus variants. Isolates consistently forming plaques of small size were associated with recently detected endemic foci with no or only sporadic reports of clinical cases. All of six virus isolates investigated in an in vivo mouse model were highly neurovirulent (100% mortality) but exhibited a relatively low level of neuroinvasiveness, with mouse survival rates ranging from 50% to 100%. Therefore, TBE viruses circulating in Switzerland belong to the European subtype and are closely related. In vitro and in vivo surrogates suggest a high proportion of isolates with a relatively low level of virulence, which is in agreement with a hypothesized high proportion of subclinical or mild TBE infections.

Dental arch relationship in 5-year-olds with complete unilateral cleft lip and palate after early alveolar bone grafting

To evaluate dental arch relationship in preschoolers with unilateral cleft lip and palate after early alveolar bone grafting (ABG).

Nasolabial symmetry and aesthetics in children with complete unilateral cleft lip and palate

The objective of this study was to evaluate the association between nasolabial symmetry and aesthetics in children with complete unilateral cleft lip and palate (CUCLP). Frontal and basal photographs of 60 consecutively treated children with CUCLP (cleft group: 41 boys and 19 girls, mean (SD) age 11 (2) years) and 44 children without clefts (control group: 16 boys and 28 girls, mean (SD) age 11(2) years), were used for evaluation of nasolabial symmetry and aesthetics. Nasal and labial measurements were made to calculate the coefficient of asymmetry (CA). The 5-grade aesthetic index described by Asher-McDade et al. was used to evaluate nasolabial appearance. Correlation and regression analysis were used to identify an association between aesthetics and CA, sex, and the presence of CUCLP. Ten measurements in the cleft, and 2 in the control, group differed significantly between the cleft and non-cleft (or right and left) sides, respectively. The significantly higher values of 9 of 11 CA in the children with CUCLP indicated that they had more asymmetrical nasolabial areas than children without clefts. However, the regression analyses showed that only a few CA were associated with nasolabial aesthetics. In conclusion, nasolabial aesthetics and nasolabial symmetry seem to be only weakly associated in patients with CUCLP.

A longitudinal three-center study of craniofacial morphology at 6 and 12 years of age in patients with complete bilateral cleft lip and palate

In this longitudinal study, the craniofacial morphology and evaluated soft tissue profile changes, at 6 and 12 years of age in patients with complete bilateral cleft lip and palate (CBCLP) were compared. Lateral cephalograms from 148 patients with CBCLP, treated consecutively at three European cleft centers, Gothenburg (n (A) = 37), Nijmegen (n (B) = 26), and Oslo (n (C) = 85), were evaluated. Eighteen hard tissue and ten soft tissue landmarks were digitized. Paired t test, Pearson's correlation coefficients, and multiple regression models were applied for statistical analysis. ANOVA and Tukey-B, as a post hoc test, were used to evaluate the increments and compare centers. Hard and soft tissue data were superimposed using the generalized Procrustes analysis. For Nijmegen, the increments of the variables SNA, ANB, SN-NL, SN-ML, NL-ML, Snss, and Snpg were significantly different than the two other centers (p = 0.041 to <0.001). SNPg increments were significantly different between Nijmegen and Oslo (p = 0.002). The three cleft centers followed different treatment protocols, but the main differences in craniofacial morphology until 12 years of age were the growth pattern and the maxillary and upper incisor variables. Follow-up of these patients until facial growth has ceased, which may elucidate components for improving treatment outcome.

Distensibility and diameter of ascending aorta assessed by cardiac magnetic resonance imaging in adults with tetralogy of fallot or complete transposition

Structural abnormalities of the medial aorta have been described for conotruncal defects (e.g., tetralogy of Fallot [TOF] and complete transposition of the great arteries (dextrotransposition [d]-TGA). In TOF, progressive aortic dilation is a frequent finding. In patients with d-TGA with an atrial switch, this problem is less often described. The aim of the present study was to compare the extent of dilative aortopathy and aortic distensibility in adults with an atrial switch procedure (n = 39) to that in adults with repaired TOF (n = 39) and controls (n = 39), using cardiac magnetic resonance imaging. The groups were matched for age and gender. Diameters of the aorta indexed to the body surface area were significantly increased in the patients with d-TGA and TOF compared to that of the controls at the aortic sinus up to the level of the right pulmonary artery. On multivariate testing, the diagnosis of a conotruncal defect (β = 0.260; p = 0.003) and aortic regurgitant fraction (β = 0.405; p <0.001) were independent predictors of an increased aortic sinus diameter. Ascending aorta distensibility was significantly reduced in those with d-TGA and TOF compared to controls: 3.6 (interquartile range 1.5 to 4.4) versus 2.8 (interquartile range 2.0 to 3.7) versus 5.5 (interquartile range 4.8 to 6.9) ×10(-3) mm Hg(-1) (p <0.001). The independent predictors of ascending aorta distensibility were the diagnosis of a conotruncal defect (p <0.001) and age (p = 0.028). In conclusion, intrinsic aortopathy, manifested as increased ascending aortic diameters and reduced ascending aortic distensibility, is not only evident in adults with TOF, but also in adults with d-TGA and an atrial switch procedure. Long-term follow-up is needed to monitor the aortic size in both patient groups.

Echocardiogram versus cardiac magnetic resonance imaging for assessing systolic function of subaortic right ventricle in adults with complete transposition of great arteries and previous atrial switch operation

In adults with congenital heart disease and a systemic right ventricle, subaortic ventricular systolic dysfunction is common. Echocardiographic assessment of systolic right ventricular (RV) function in these patients is important but challenging. The aim of the present study was to assess the reliability of conventional echocardiographic RV functional parameters to quantify the systolic performance of a subaortic right ventricle. We compared 56 contemporary echocardiograms and cardiac magnetic resonance studies in 37 adults, aged 26.9 ± 7.4 years, with complete transposition and a subaortic right ventricle. The fractional area change (FAC), lateral tricuspid annular plane systolic excursion, lateral RV systolic motion velocities by tissue Doppler, RV myocardial performance index, and the rate of systolic RV pressure increase (dp/dt) measured across the tricuspid regurgitant jet were assessed by echocardiography and correlated with the cardiac magnetic resonance-derived RV ejection fraction (EF). The mean RVEF was 48.0 ± 7.8%. FAC (r(2) = 0.206, p = 0.001) and dp/dt (r(2) = 0.173, p = 0.009) significantly correlated with RVEF, and the other nongeometric echocardiographic parameters failed to show a significant correlation with RVEF by linear regression analysis. FAC <33% and dp/dt <1,000 mm Hg/s identified a RVEF of <50% with a sensitivity of 77% and 69% and a specificity of 58% and 87%, respectively. In conclusion, in patients with a systemic right ventricle, routine nongeometric echocardiographic parameters of RV function correlated weakly with cardiac magnetic resonance-derived EF. RV FAC and the measurement of the rate of systolic RV pressure increase (dp/dt) should be preferentially used to assess systemic systolic function in adult patients with a subaortic right ventricle.

Family Anomie and Juvenile Deliquency in Post-Communist Romania

The sensitivity of crime rates to social, economic and political influences has long aroused the interest of sociologists who have attempted to explain what kind of relationships might be associated with variations in crime rates between different social groups at different times. The earliest views were put forward by Emil Durkheim, and while later writers have developed (R.K. Merton, L. Srole, A, K. Cohen, etc.) have developed some aspects of his ideas further, his basic ideas of the divorce of the individual from normative standards and the lack of social integration are still valid. Ms. Voicu-Minea looked at the theoretical background in detail but then limited it to a specific social group, the family, asking first why certain individual within vulnerable families and/or negative social influences commit offences while others do not. In modern times the family has undergone massive structural and functional changes. Its former economic function, which once endowed it with a great capacity for social inclusion, has generally vanished, while its formerly crucial role in children's education has been massively reduced. These changes, which are still not complete, can lead to dysfunction and in certain social contexts such as that in post-communist Romanian society, this risk of dysfunction is still greater as unfavourably social circumstances more easily affect such families. The number of cases of juvenile delinquency in Romania has increased sharply ever since the end of the communist system and in 1996 reached the level of 18,317 cases. The sample examined included 1012 juvenile delinquents aged between 14 and 18, taken from all areas of Bucharest. Over 80% of charges related to theft, with more serious offences being relatively rare. The children underwent a series of psychological tests, accompanied by a questionnaire relating to family situation. The results showed that juvenile delinquency in Romania is overwhelmingly male, with 91.8% of offences being committed by boys. Two thirds of the research group were under the age of 16 and only just over one third attended school, with over half having left school before the legal age. While the majority of subjects had a lower than average level of education, they did not always recognise this, with two thirds seeing their level of education as being as good as or better than average. Nearly half the children (43%) did not live with both natural parents and majority came from families with three or more children. This applied both to their original families and to the families in which they were living at the time of the survey. The overwhelming majority of families were living in or around Bucharest, but under one third originated from there. Almost 25% of parents were under-schooled and around one third were unqualified workers. At least 30% of families lived in inadequate accommodation and family incomes were generally low. Ms. Voicu-Minea does however point out that over half the minors from the sample saw their family income as satisfactory or even more than satisfactory. When factors such as bad relationships between parents, corporal punishment, alcohol consumption and criminal records of family members were taken into account, the picture was bleak, making it understandable why over 36% of subjects had run away from home at least once, and in many cases repeatedly and for longer periods. The overwhelming majority of offences (80.8%) were committed in groups of between 2 and 11 persons, usually "friends" but in about 10% of cases member's of the family. IQ tests put about 75% of the sample at slightly under average, the difference being too slight to account for the behaviour problems of the majority. Personality tests, however, showed a different picture. Over 70% of those tested manifested an acute need of tenderness and a similar number a high level of potential aggressiveness. Almost half of the minors expressed such feelings as intolerance or a desire for revenge, and Ms. Voicu-Minea found a clear weakness of the Self. Around half the sample expressed sentiments of abandonment, renunciation and solitude.