Expanding CEP290 mutational spectrum in ciliopathies.

Ciliopathies are an expanding group of rare conditions characterized by multiorgan involvement, that are caused by mutations in genes encoding for proteins of the primary cilium or its apparatus. Among these genes, CEP290 bears an intriguing allelic spectrum, being commonly mutated in Joubert syndrome and related disorders (JSRD), Meckel syndrome (MKS), Senior-Loken syndrome and isolated Leber congenital amaurosis (LCA). Although these conditions are recessively inherited, in a subset of patients only one CEP290 mutation could be detected. To assess whether genomic rearrangements involving the CEP290 gene could represent a possible mutational mechanism in these cases, exon dosage analysis on genomic DNA was performed in two groups of CEP290 heterozygous patients, including five JSRD/MKS cases and four LCA, respectively. In one JSRD patient, we identified a large heterozygous deletion encompassing CEP290 C-terminus that resulted in marked reduction of mRNA expression. No copy number alterations were identified in the remaining probands. The present work expands the CEP290 genotypic spectrum to include multiexon deletions. Although this mechanism does not appear to be frequent, screening for genomic rearrangements should be considered in patients in whom a single CEP290 mutated allele was identified.

Spinal muscular atrophy. Incidence in Iceland.

Spinal muscular atrophy (SMA) is among the commonest degenerative disorders of the nervous system in childhood. This is an inherited autosomal recessive disease which results in premature death of anterior horn cells of the spinal cord and is manifested by progressive weakness and atrophy of skeletal muscles. Few studies have looked at the frequency of the disease in a defined population. We identified all patients diagnosed with SMA in Iceland during a 15-year period. The diagnosis is based on typical symptoms and supported by results of electromyography/nerve conduction studies and muscle biopsy. The average annual incidence was 13.7 per 100,000 live births for all types of SMA, which is similar to that reported in other population-based studies.

Paediatric burns in Iceland. Hospital admissions 1982-1995, a populations based study.

Epidemiological data of 290 children admitted to the Paediatric Department, University Hospital of Iceland, over a 14 year period, 1982-1995, are presented. The sex ratio boys/girls was 1.6. 72.8% were children four years and younger. Hot fluids was the most common cause of burn injuries, mostly caused by geothermal hot water. Only one child suffered from electricity burn injuries and none from corrosives. Most of the accidents occurred at home (81.4%). A decreasing number of children suffering from electricity and corrosive burn injuries reflects heightened awareness and improved safety in the home. We found a significant increase in the incidence of hot fluid burn injuries in Icelandic children compared to previous studies. This calls for preventive measures with regard to geothermal and other hot water burns in Icelandic children.

Rolandic epilepsy: an incidence study in Iceland.

PURPOSE: We wished to determine incidence, clinical features, and prognosis of benign rolandic seizures (BRS) and benign rolandic epilepsy (BRE) in a total population. METHODS: Cases were ascertained through review of all EEG records, and diagnosis was verified by review of medical records. Follow-up information regarding seizures and treatment was obtained from parents and treating physicians. RESULTS: In the Icelandic population aged 3-15 years, the incidence of BRS is 6.2 and BRE 4.7 in 100,000. Five years after onset 95% were seizure-free. At last follow-up, all were seizure free and had not been treated with antiepileptic drugs (AEDs) for at least 1 year. CONCLUSIONS: Our study demonstrates that BRS is a common entity in children. The prognosis is excellent and treatment is not necessary in all cases. It is important to identify BRE/BRS correctly and distinguish it from other types of epilepsy.

Pregnancies of women with epilepsy: a population-based study in Iceland.

PURPOSE: Women with epilepsy who become pregnant are commonly considered to be at high risk for complications during pregnancy or delivery. The offspring are also considered to have increased risk of perinatal mortality, congenital malformations, and maturational delay. Because few of these studies are population based, potential bias exists because of selection. METHODS: We performed a historical population-based cohort study in Iceland to determine the prevalence of epilepsy among pregnant women, to identify pregnancy and delivery complications in women with epilepsy, and to determine the outcome of their pregnancies as compared with that in the general population of Iceland. We identified all women with active epilepsy who gave birth during a 19-year period in Iceland. RESULTS: In this population, 3.3 in 1,000 pregnancies involve mothers with active epilepsy. The frequency of adverse events (AE) during pregnancy in the women with epilepsy is similar to that observed among all live births in the population, but cesarean section was performed twice as frequently as in the general population. Perinatal mortality rate and mean birth weight are not significantly different in the offspring of women with epilepsy as compared with rest of the population. The risk of major congenital malformations (MGM) is increased 2.7-fold over that expected when a mother is treated with antiepileptic drugs (AEDs) during a pregnancy. CONCLUSIONS: Our study indicates that the rate of complications of pregnancy in mothers with active epilepsy is low and similar to that of the general population with epilepsy. Use of AEDs by the mother during pregnancy significantly increases the risk of MGM in the offspring.

[Burn injuries in children in Iceland between 1982-1995.].

OBJECTIVE: To increase our knowledge of burn injuries in children in Iceland and to induce education and prevention in order to reduce the incidence of burn injuries among children. MATERIAL AND METHODS: Data was collected from hospital records of all children 15 years and younger admitted with burn injuries to the University Hospital of Iceland, Paediatric Department, from 1982-1995. RESULTS: There were 290 children admitted, 179 boys and 111 girls, sex ratio 1.6. Children four years and younger were 72.8%. Approximately 21 children were admitted annually. Seasonal variation was noted with most admittances in December. The times when the injuries occurred peaked at lunch and dinner times. Scalds was most common, hot water caused 45.8% of the burn injuries, most frequently due to bathwater (15.2%). Hot liquids caused 26.9%, most often caused by coffee-, tea- and cacao drinks (19.3%). Flames caused 12.4% of the burn injuries, fireworks 5.5% and hot object 5.2%. Most of these accidents occurred at home (81.4%). CONCLUSION: Children four years and younger are most susceptible for burn injuries. Hot water and liquids caused most of these burn injuries. Burn injuries are common in childhood. Our data provide basis for better prevention.

Incidence of epilepsy in rural Iceland: a population-based study.

PURPOSE: We wished to determine the incidence of epilepsy in the population of rural Iceland. METHODS: Cases were identified through review of records of primary care facilities for the study population, supplemented by review of referrals to EEG facilities and neurologic specialists. RESULTS: The incidence of epilepsy (recurrent unprovoked seizures) was 47 in 100,000. Age-specific incidence was bimodal, highest in the youngest and oldest age groups. About one third of the patients had an identifiable etiology, and one third had partial seizures. Integration of imaging and neurophysiologic data did little to modify the distribution of etiology or seizure type. CONCLUSIONS: The present study confirms findings of other recent studies of incidence in Western Countries.

[Isovaleric acidemia]. / Isovalerianacidaemi.

The three first cases of isovaleric acidemia diagnosed in Scandinavia are described. The disorder is characterized by periodic vomiting, lethargy and coma accompanied by ketoacidosis and a "sweaty feet" odour. These attacks are often triggered of by upper respiratory tract infections or by ingestion of large amounts of protein. Often there are feeding difficulties because these children have aversion to protein-containing foods. Isovaleric acidemia can be subdivided into two types: an acute neonatal form and a chronic intermittent form. The basic defect is deficient activity of isovaleryl-CoA dehydrogenase, resulting in increased urinary excretion of mainly isovaleryl-glycine and 3-hydroxy-isovaleric acid. The defective gene is assigned to the long arm of chromosome 15, and at least five different mutations among 15 patients have been demonstrated. Therapy is symptomatic with correction of the metabolic acidosis and protein restriction and long term treatment with oral glycine and possibly carnitine.

Three cases of neonatal meningitis caused by Enterobacter sakazakii in powdered milk.

Three cases of neonatal infection caused by Enterobacter sakazakii are reported from the Department of Neonatal Intensive Care, the National University Hospital, Reykjavík, Iceland. These infections occurred during a 9-month period in 1986 and 1987. Two of the neonates, who were normal at birth, survived but were left with brain damage. The third, who had Down's syndrome and severe cardiac malformations, died. The same organism was also grown from groin and anal swabs from a healthy neonate. E. sakazakii was not isolated from any environmental sources in the neonatal wards or in the milk kitchen, but it was grown from several lots of the powdered-milk formula used in the hospital. The four E. sakazakii strains isolated from the neonates were indistinguishable from 22 strains grown from the formula. Their biotypes, plasmid DNA profiles, and antibiograms were identical.

Bacterial meningitis: diagnosis and initial antibiotic therapy.

Despite advances in antibiotic treatment, bacterial meningitis remains a significant cause of mortality and morbidity among children. In population-based studies in the United States, the incidence of bacterial meningitis is estimated to be 4.6 to 10 per 100,000 population per year. Every year more than two thousand deaths due to bacterial meningitis are reported in the United States, most of these in previously healthy children. This article reviews diagnosis and management of this puzzling disease entity.