The Aicardi-Goutières syndrome: Variable clinical expression in two siblings

We report 2 siblings with the Aicardi-Goutières syndrome (encephalopathy, basal ganglia calcifications, and persistent cerebrospinal fluid pleiocytosis). The eldest sibling is severely retarded; his younger brother has only mild, slowly progressive neurological deficits. To our knowledge, such a striking difference in clinical expression has not been reported previously.     

POMT2 mutations cause alpha-dystroglycan hypoglycosylation and Walker-Warburg syndrome

Background: Walker-Warburg syndrome (WWS) is an autosomal recessive condition characterised by congenital muscular dystrophy, structural brain defects, and eye malformations. Typical brain abnormalities are hydrocephalus, lissencephaly, agenesis of the corpus callosum, fusion of the hemispheres, cerebellar hypoplasia, and neuronal overmigration, which causes a cobblestone cortex. Ocular abnormalities include cataract, microphthalmia, buphthalmos, and Peters anomaly. WWS patients show defective O-glycosylation of α-dystroglycan (α-DG), which plays a key role in bridging the cytoskeleton of muscle and CNS cells with extracellular matrix proteins, important for muscle integrity and neuronal migration. In 20% of the WWS patients, hypoglycosylation results from mutations in either the protein O-mannosyltransferase 1 (POMT1), fukutin, or fukutin related protein (FKRP) genes. The other genes for this highly heterogeneous disorder remain to be identified. Objective: To look for mutations in POMT2 as a cause of WWS, as both POMT1 and POMT2 are required to achieve protein O-mannosyltransferase activity. Methods: A candidate gene approach combined with homozygosity mapping. Results: Homozygosity was found for the POMT2 locus at 14q24.3 in four of 11 consanguineous WWS families. Homozygous POMT2 mutations were present in two of these families as well as in one patient from another cohort of six WWS families. Immunohistochemistry in muscle showed severely reduced levels of glycosylated α-DG, which is consistent with the postulated role for POMT2 in the O-mannosylation pathway. Conclusions: A fourth causative gene for WWS was uncovered. These genes account for approximately one third of the WWS cases. Several more genes are anticipated, which are likely to play a role in glycosylation of α-DG.     

Development and psychometric evaluation of the TAPQOL: A health-related quality of life instrument for 1–5-year-old children

The 43-item TNO-AZL Preschool Children Quality of Life (TAPQOL) questionnaire was developed to meet the need for a reliable and valid instrument for measuring parent's perceptions of health-related quality of life (HRQoL) in preschool children. HRQoL was defined as health status in 12 domains weighted by the impact of the health status problems on well-being. The aim of this study was to evaluate the psychometric performance of the TAPQOL. A sample of 121 parents of preterm children completed the TAPQOL questionnaire (response rate 88%) as well as 362 parents of children from the general population (response rate 60%). On the base of Cronbach's α, item-rest correlation, and principal component analysis, the TAPQOL scales were constructed from the data for the preterm children sample. The psychometric performance of these scales was evaluated for both the preterm children sample and the general population sample. Cronbach's α ranged from 0.66 to 0.88 for the preterm children sample and from 0.43 to 0.84 for the general population sample. The unidimensionality of the separate scales was confirmed by principal component analysis for both the preterm children sample and the general population sample. Spearman's correlation coefficients between scales were, on average, low. T-tests showed that the very preterm children, the children with chronic diseases, the less healthy and the less happy children had lower mean scores on the TAPQOL scales than healthy children, indicating a worse quality of life. This study shows that the TAPQOL is a reliable and valid parent's perception of HRQoL in preschool children. More research is needed to evaluate the psychometric performance of the TAPQOL in different clinical populations. This revised version was published online in June 2006 with corrections to the Cover Date.     

Periodontal disease and quality of life

In order to gain insight into the degree to which periodontal disease is related to quality of life, research was carried out among 85 patients with moderate or severe periodontal disease in which they were asked to complete the Oral Health Impact Profile-NL49. Their scores on this questionnaire were compared with the scores of 85 control subjects of comparable age and gender. The patients with periodontal disease demonstrated significantly worse scores compared to the control group and patients with severe periodontal disease had scores which were statistically significantly worse than patients with moderate periodontal disease. The results of this study suggest a causal negative association of periodontal disease with quality of life.     

The complexity of the concept oral health-related quality of life

The methods uses most often for developing and analyzing questionnaires, such as the explorative factor analysis and Cronbach's alpha, presume that psychological constructs are latent (imperceptible) and that there is a reflective-measurement model with the underlying assumption of local independence. Local independence means that the latent variable explains why the variables observed are related. Many questionnaires for measuring oral health-related quality of life are analyzed as if they were based on a reflective-measurement model assuming local independence. This assumption requires these questionnaires to contain solely items reflecting instead of determining oral health-related quality of life. The tenability of this assumption is questionable.     

A previously healthy 11-year-old girl with behavioural disturbances, desquamation of the skin and loss of teeth

An 11-year-old girl was admitted with backpain, weight loss, fatigue and behavioural disturbances, starting seven weeks before admission. Physical examination showed acrodynia, tremor, cachexia, hypertension and extensive gingival ulceration. Routine laboratory tests were normal, except for a CRP of 98 mg/l. Screening tests for recreational drugs as well as antibody assays for HIV, hepatitis B and borrelia burgdorferia were negative. Chest X-ray, brain CAT and MRI scan were all normal. Lumbar puncture didn’t show any abnormalities. Eventually a 24-hour urine test confirmed the diagnosis that was suspected by further questioning.     

Treatment and follow-up of children with cerebrotendinous xanthomatosis

The clinical spectrum and the effects of treatment over a period of 5 years in five children with cerebrotendinous xanthomatosis (CTX) are described. In all children biochemical, neuroradiological, and neurophysiological studies were done. CTX was diagnosed and effects of therapy were evaluated by determination of the serum cholestanol/cholesterol ratio (CCR) and the urinary excretion of bile alcohols. All children were treated with chenodeoxycholic acid (15 mg/kg/day) in three divided oral doses. Diarrhoea and juvenile cataract were the main clinical features. Psychomotor retardation, pyramidal and cerebellar signs were also found. After starting treatment, biochemical abnormalities normalized and diarrhoea disappeared. After 1 year of therapy there was no further delay in motor development, and in three children the intelligence quotient improved. EEG abnormalities disappeared. After 5 years of therapy the children are in a stable clinical condition. Conclusion The clinical, biochemical and neurophysiological abnormalities in five children with CTX showed a remarkable improvement after starting treatment with chenodeoxycholic acid. The early diagnosis of CTX and the start of treatment with chenodeoxycholic acid has prevented neurological deterioration for a period of 5 years. Received: 24 May 1997 / Accepted in revised form: 29 September 1997     

Changes in oral health in adults. Results of studies performed in 1983 and 1995

In 1995 a dental survey among adults aged 25-54 years was performed in 's-Hertogenbosch (The Netherlands). Aim was to study trends in oral health after 1983, a year in which a similar study was performed in the same city. Caries data were obtained by clinical examination only. The percentage of edentulous persons in the sample decreased with about 50% between 1983 and 1995. In 1995 in all age categories of dentate persons, the mean number of FT was higher, and the mean numbers of DT and MT were lower than in 1983. In persons with a natural dentition under the age of 35 the mean number of DMFT decreased significantly. It was concluded that oral health in adults living in 's-Hertogenbosch, as measured by caries prevalence, treatment level of caries and percentage of edentulous persons, improved significantly between 1983 and 1995. It is supposed that the trends found in 's-Hertogenbosch are indicative of changes in oral health in The Netherlands.     

Oral health and ethnicity. An epidemiologic investigation in 5- and 11-year-olds in Amsterdam

This study investigates whether the oral health of 5- and 11-year-old children of immigrants from Turkey and Morocco is worse than that of Dutch peer groups in Amsterdam. The outcome variables considered were dmft/s. DMFT/S and the index-components, amount of plaque and number of tooth surfaces sealed (only 11-year olds). The explanatory variable considered was ethnicity (Turkish, Moroccan, Dutch, Surinam and 'Others'). The mean dmfs-score of Turkish and Moroccan 5-year olds was significantly higher than that of Dutch children: 8.1 and 8.2 vs. 3.6, respectively. Also a significant difference in mean DMFS-score between Turkish and Dutch 11-year olds was found; 3.3 vs. 1.7, but not between Moroccan and Dutch children. On average 1.8 surfaces were found sealed in 11-year olds. The mean plaque scores observed in Turkish and Moroccan five- and 11-year olds was significantly higher than in Dutch children. It was concluded that the oral health of Turkish and Moroccan children in Amsterdam was worse than that of their Dutch peer groups and that programs should be developed aimed at improving this situation.