Dental maturation in children with shunt-treated hydrocephalus.

OBJECTIVE: The aim of this study was to examine the relationship between dental maturation and somatic development and to discover their possible deviations in children with shunt-treated hydrocephalus. DESIGN: Radiographs (orthopantomogram and hand-wrist radiograph) from children with shunt-treated hydrocephalus were analyzed with respect to the dental maturation and compared with values of an age- and sex-matched control group and population standards. PATIENTS: Forty-one children with shunt-treated hydrocephalus (27 boys and 14 girls) aged from 5 to 16 years (median age 11.0 years). RESULTS: The mean deviation of dental age from chronological age was significantly greater in the hydrocephalic group than in the control group. The mean value of dental age deviation was advanced in early pubertal stages but reduced in later pubertal stages. CONCLUSIONS: These findings can be explained by changes in the endocrinological conditions, which are due to disturbed pituitary secretion. The present results could also partly reflect an adaptable developmental pathway in an otherwise strictly genetically determined process.

Multiple founder effects and geographical clustering of BRCA1 and BRCA2 families in Finland.

In the Finnish breast and ovarian cancer families six BRCA1 and five BRCA2 mutations have been found recurrently. Some of these recurrent mutations have also been seen elsewhere in the world, while others are exclusively of Finnish origin. A haplotype analysis of 26 Finnish families carrying a BRCA1 mutation and 20 families with a BRCA2 mutation indicated that the carriers of each recurrent mutation have common ancestors. The common ancestors were estimated to trace back to 7-36 generations (150-800 years). The time estimates and the geographical clustering of these founder mutations in Finland are in concordance with the population history of this country. Analysis of the cancer phenotypes showed differential ovarian cancer expression in families carrying mutations in the 5' and 3' ends of the BRCA1 gene, and earlier age of ovarian cancer onset in families with BRCA1 mutations compared with families with BRCA2 mutations. The identification of prominent and regional BRCA1 and BRCA2 founder mutations in Finland will have significant impact on diagnostics in Finnish breast and ovarian cancer families. An isolated population with known history and multiple local founder effects in multigenic disease may offer distinct advantages also for mapping novel predisposing genes.

Pituitary function in children with hydrocephalus before and after the first shunting operation.

OBJECTIVE: Children with shunted hydrocephalus experience slow linear growth in prepuberty, accelerated pubertal maturation and a reduced final height. A substantial proportion of these patients have a poor growth hormone (GH) response to stimulation and reduced pituitary volume. The basic mechanisms behind these phenomena are still unknown, but one can hypothesize that an unphysiological intracranial pressure (ICP) may be involved. This study was undertaken to investigate the effect of increased ICP on pituitary function. DESIGN: Twenty-one children (nine males) aged 4 months to 15 years were evaluated for pituitary function before and after their first shunting operation. METHODS: A clinical examination was performed, bone age was determined and a combined pituitary stimulation test was performed to evaluate GH, luteinizing hormone, follicle-stimulating hormone, cortisol, thyrotropin and prolactin secretion. RESULTS: GH concentrations were significantly higher 10 and 15 min before the operation (P=0.04 and P=0.03 respectively) than after it. The basal levels of insulin-like growth factor-I (IGF-I) tended to be higher before the operation than afterwards and those of its binding protein-3 (IGFBP-3) were significantly so (P<0.01). CONCLUSIONS: The higher GH response to GH releasing hormone and circulating IGFBP-3 levels in children with hydrocephalus before compared with after their first shunting operation raise the possibility that the reduced GH secretion and retarded linear growth observed in children with shunted hydrocephalus may be a consequence of decreased ICP and/or the lack of physiological pressure variations.

Prediction of insulin-dependent diabetes mellitus in siblings of children with diabetes. A population-based study. The Childhood Diabetes in Finland Study Group.

An unselected population of 755 siblings of children with insulin-dependent diabetes mellitus (IDDM) was studied to evaluate the predictive characteristics of islet cell antibodies (ICA), antibodies to the IA-2 protein (IA-2A), antibodies to the 65-kD isoform of glutamic acid decarboxylase (GADA), insulin autoantibodies (IAA), and combinations of these markers. We also evaluated whether the histochemical ICA test could be replaced by the combined detection of other markers. 32 siblings progressed to IDDM within 7.7 yr of the initial sample taken at or close to the diagnosis of the index case (median follow-up, 9.1 yr). The positive predictive values of ICA, IA-2A, GADA, and IAA were 43, 55, 42, and 29%, and their sensitivities 81, 69, 69, and 25%, respectively. In contrast to the other three antibody specificities, GADA levels were not related to the risk for IDDM. The risk for IDDM in siblings with four, three, two, one, or no antibodies was 40, 70, 25, 2, and 0.8%, respectively. Combined screening for IA-2A and GADA identified 70% of all ICA-positive siblings, and all of the ICA-positive progressors were also positive for at least one of the three other markers. The sensitivity of the combined analysis of IA-2A and GADA was 81%, and the positive predictive value was 41%. In conclusion, combined screening for IA-2A and GADA may replace the ICA assay, giving comparable sensitivity, specificity, and positive predictive value. Accurate assessment of the risk for IDDM in siblings is complicated, as not even all those with four antibody specificities contract the disease, and some with only one or no antibodies initially will progress to IDDM.

Reduced levels of growth hormone, insulin-like growth factor-I and binding protein-3 in patients with shunted hydrocephalus.

OBJECTIVE: Children with hydrocephalus are characterised by slow linear growth in prepuberty, accelerated physical maturation during puberty, and reduced final height. We aimed to study the possible roles of growth hormone, insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3) in this growth pattern. STUDY DESIGN: One hundred and fourteen patients with shunted hydrocephalus (62 males) aged 5 to 20 years, of whom 17 had spina bifida (six males), and 73 healthy controls (38 males) were studied. Anthropometric measures, body mass index, and body fat mass were assessed and the stage of puberty was determined. Serum growth hormone and plasma IGF-I and IGFBP-3 concentrations were measured. RESULTS: The patients comprised 44 (26 males) who were prepubertal and 70 (36 males) pubertal or postpubertal, while 32 of the controls (19 males) were prepubertal and 41 (19 males) pubertal or postpubertal. The prepubertal children with hydrocephalus had lower IGF-I (p = 0.002) and IGFBP-3 concentrations (p < 0.001) than the controls, and the pubertal children had four times lower basal growth hormone concentrations (p < 0.001). There was a correlation between height SD score and IGF-I levels in the total patient population (r = 0.23; p = 0.01). Peripheral IGF-I concentrations peaked at pubertal stages 2-3 in the female patients and at stage 4 in the controls. The prepubertal patients on antiepileptic treatment, carbamazepine in most cases (73%), had higher IGF-I (p = 0.01) and IGFBP-3 concentrations (p = 0.03) than those who had never been treated with antiepileptic drugs, but still lower IGFBP-3 levels than the controls (p = 0.01). CONCLUSION: Based on these findings, it can be concluded that reduced growth hormone secretion may contribute to the pattern of slow linear growth and reduced final height observed in these patients.

Pituitary size and function in children and adolescents with shunted hydrocephalus.

OBJECTIVE: Most previous reports of endocrine disorders in children with shunted hydrocephalus have been case reports and there is a lack of systematic information on pituitary anatomy and function among these children. We have obtained these data in a large group of individuals with shunted hydrocephalus. DESIGN: A controlled cross-sectional study. PATIENTS: Fifty-four children and adolescents with shunted hydrocephalus were studied for pituitary anatomy and function. They had 54 age- and sex-matched controls (group I). The mean age of the patients and controls was 12.6 years and the mean shunting period 10.6 years. There was a second control group (II) for the magnetic resonance imaging (MRI) and a third control group (III) for the radiography of the sella turcica. MEASUREMENTS: The anatomy was visualized by MRI of the pituitary gland and by radiography of the sella turcica. The functional evaluation included an arginine-insulin test and a combined stimulation test with corticotrophin releasing factor (CRF), GnRH and TRH. RESULTS: The patients were shorter (height 148.4 cm vs 153.7 cm, P < 0.05 and relative height -0.5 SDS vs 0.4 SDS, P < 0.05) and had a higher BMI than the control group I (20.6 kg/m2 vs 18.0 kg/m2, P < 0.001). They had also a greater pituitary height than the control group II (5.8 mm vs 5.1 mm, P < 0.01). The patients had significantly lower basal GH levels (P < 0.001) than controls I. Sixteen patients (30%) had a poor GH response (< 20 mU/l) in the arginine-insulin test. Pituitary height was significantly lower among these patients than in those with a normal response (4.7 mm vs 6.3 mm, P < 0.01), who had an increased pituitary height compared to controls II (5.1 mm, P < 0.01). The area under the curve (AUC) for GH correlated with the pituitary volume (r = 0.50, P < 0.001). The patients had higher basal FSH and LH concentrations than controls I (P < 0.001). The peak to basal ratios of FSH and LH were increased in the prepubertal patients and that of LH at Tanner pubertal stage II in the females. The basal FSH and LH levels correlated with the pituitary volume (r = 0.50 and r = 0.54, P < 0.001 for), as did FSH AUC and LH AUC (r = 0.48 and r = 0.75, P < 0.001 for both). CONCLUSIONS: These observations indicate that children with shunted hydrocephalus have an increased pituitary size on average. About one-third of these patients had signs of reduced GH secretion and significantly lower pituitary height, which probably contributes to their poor linear growth. Increased pituitary size was associated with enhanced gonadotrophin secretion, which may result in early puberty in children with shunted hydrocephalus.

Snoring children: factors predicting sleep apnea.

Many snoring children present obstructive symptoms according to their parents. The seriousness of the symptoms and the possibility of the obstructive sleep apnea syndrome (OSAS) in these children may be difficult to judge on the basis of the clinical findings and the patient's history only. In order to evaluate snoring children's relative risk (RR) to have OSAS, their symptoms and signs, as reported by the parents, and clinical findings were compared with the results of overnight polysomnography (PSG). An obstructive apnea index (AI) > or = 1 in PSG was regarded as the criterion for OSAS. The mean AI was 1.55 (range 0-15), and 29 children had a pathological AI, while 49 had a normal PSG recording. Apneic episodes every night detected by the parents was the most important single risk factor for OSAS (RR 3.6, 95% confidence interval (CI) 1.7-7.7). The RR ratio decreased when apneas appeared less frequently, but any detected apnea was still a single risk factor (RR 1.4, CI 1.2-1.8). The other risk factors of night-time symptoms were constant snoring (RR 1.5, CI 1.0-2.1) and restless sleep (RR 2.1, CI 1.1-4.0). Of the daytime symptoms, absence of excessive sleepiness was a protective factor against OSAS (RR 0.3, CI 0.1-1.0). Previous adenoidectomy was found to be a risk factor (RR 1.7, CI 1.1-2.7), as was tonsillar enlargement (RR 1.4, CI 1.1-1.8). These two findings suggest that the epipharyngeal space does not play a central role in the development of OSAS in children. OSAS cannot be reliably diagnosed without PSG, which is the most important examination for snoring children with obstructive symptoms. For clinical decisions, the consideration of risk factors is essential.

Accelerated pubertal development in patients with shunted hydrocephalus.

OBJECTIVE: To evaluate pubertal development and peripheral concentrations of gonadotrophins and sex hormones in children with shunted hydrocephalus compared with healthy controls. STUDY DESIGN: 114 patients (52 females, 62 males) and 73 healthy controls (35 females, 38 males) aged 5 to 20 years were analysed for stage of puberty, age at menarche, testicular volume, basal serum follicle stimulating hormone (FSH), luteinising hormone (LH), sex hormone binding globulin (SHBG), testosterone and oestradiol concentrations, and free androgen index. RESULTS: Male gonadal and male and female pubic hair development occurred significantly earlier in the patients than in the controls. The mean age at menarche was significantly lower in the female patients than in their controls (11.7 v 13.2 years; p < 0.001), and lower than it had been for their mothers (v 13.1 years; p < 0.001). Relative testicular volume was higher in the male patients than in their controls (1.2 standard deviation score (SDS) v 0.2 SDS; p < 0.001). The prepubertal patients had higher basal LH (0.13 U/l v 0.08 U/l; p < 0.001) and SHBG (132.3 nmol/l v 109.1 nmol/l; p < 0.01) than the controls. Both the prepubertal and pubertal females had significantly higher basal FSH than their controls (1.57 U/l v 1.03 U/l; p < 0.05, and 4.0 U/l v 2.9 U/l; p < 0.01, respectively). CONCLUSIONS: Hydrocephalic children experience accelerated pubertal maturation, reflected in a younger age at menarche in females and an increased testicular volume in males. This may be because of enhanced gonadotrophin secretion, possibly resulting from unphysiological variations in intracranial pressure.

Slow prepubertal linear growth but early pubertal growth spurt in patients with shunted hydrocephalus.

OBJECTIVE: To evaluate growth and to compare anthropometric measures and the degree of physical maturation in children with shunted hydrocephalus with those in healthy children. METHODS: One hundred fourteen patients (62 male) and 73 healthy subjects (38 male) 5 to 20 years of age were analyzed for growth data and current auxology, stage of puberty, and bone age. RESULTS: Boys with hydrocephalus were shorter than control boys during their first 8 years of age, and no catch-up growth was observed until puberty. Girls with hydrocephalus were of the same size at birth as the control girls, but their linear growth retarded during the first years of life, leading to reduced relative height between the age of 5 to 8 years. The pubertal growth spurt occurred earlier in boys with hydrocephalus (age at midgrowth spurt, 12.1 vs 13.3 years), and a similar trend was seen in girls (10.0 vs 10.7 years). The final height was again reduced, especially in boys. Patients with hydrocephalus were more obese than control subjects, girls more often than boys. Relative bone age was retarded in prepubertal (-0.42 vs 0.32 SD) and accelerated in pubertal patients (0.54 vs -0.19 SD). CONCLUSIONS: Children with hydrocephalus experience slow linear growth in prepuberty, but they have an earlier adolescent growth spurt. Together these factors result in a reduced final height. An increase in relative weight emerges in the preadolescent period, and this phenomenon is accentuated after puberty, leading to an increased prevalence of obesity.

Information value of magnetic resonance imaging in shunted hydrocephalus.

OBJECTIVE: To study the role of magnetic resonance imaging (MRI) in evaluating children with shunted hydrocephalus. METHODS: Sixty one asymptomatic children with shunted hydrocephalus or cystic cerebrospinal fluid collections were studied by cranial MRI. The information obtained from the images was classified into three categories: provided (1) a new diagnosis, (2) additional information, or (3) no essential new information. The findings were compared with those of the last follow up computed tomograms. RESULTS: MRI provided a new diagnosis in seven cases (11.5%), and additional information was obtained in 34 (55.7%) cases. In 20 cases (32.8%) no essential new information was obtained. MRI visualised white matter lesions and corpus callosum pathology more often than computed tomograms. CONCLUSIONS: MRI provided new important information in cases of children with shunted hydrocephalus to such an extent that it can be recommended as the primary imaging method for every child with this disorder.