Faruk Incecik

Functional genome-wide siRNA screen identifies KIAA0586 as mutated in Joubert syndrome.

Defective primary ciliogenesis or cilium stability forms the basis of human ciliopathies, including Joubert syndrome (JS), with defective cerebellar vermis development. We performed a high-content genome-wide small interfering RNA (siRNA) screen to identify genes regulating ciliogenesis as candidates for JS. We analyzed results with a supervised-learning approach, using SYSCILIA gold standard, Cildb3.0, a centriole siRNA screen and the GTex project, identifying 591 likely candidates. Intersection of this data with whole exome results from 145 individuals with unexplained JS identified six families with predominantly compound heterozygous mutations in KIAA0586. A c.428del base deletion in 0.1% of the general population was found in trans with a second mutation in an additional set of 9 of 163 unexplained JS patients. KIAA0586 is an orthologue of chick Talpid3, required for ciliogenesis and Sonic hedgehog signaling. Our results uncover a relatively high frequency cause for JS and contribute a list of candidates for future gene discoveries in ciliopathies. DOI: http://dx.doi.org/10.7554/eLife.06602.001

Evaluation of nine children with reversible posterior encephalopathy syndrome.

BACKGROUND Reversible posterior leukoencephalopathy syndrome (PRES) is a neurological disorder characterized by signs of posterior cerebral edema upon radiographic examination. MATERIALS AND METHODS We retrospectively analyzed the records of nine children with the diagnosis of PRES. RESULTS Of the nine patients, seven were receiving immunosuppressive therapy and two were acute hypertensive crisis associated with renal disease. Immunosupressive drugs were intrathecal methotrexate in two patients, cyclosporine in two patients, intrathecal cytarabine in one patient, cyclophasphamide in one patient, and intravenous immunoglobulin (IVIg) in another one patient. The most presenting symptoms were seizure, headache, and altered consciousness. Six patients had seizures. Altered consciousness was present in four patients. Headache and nausea or vomiting was present also in six patients. Visual abnormalities were noted in two patients. Magnetic resonance imaging (MRI) studies showed white-matter abnormalities suggestive of edema in the posterior regions of the cerebral hemispheres, but the changes often involved other cerebral areas, the brain stem, basal ganglia or the cerebellum. The patients were treated with antihypertensive medications, and immunosuppressive therapy was withdrawn. In all the patients, the clinical and radiological findings resolved more completely. CONCLUSION Reversible posterior leukoencephalopathy may develop in patients who have renal insufficiency or hypertension or who are immunosuppressed. This syndrome should be recognized immediately and trigger agents can be discontinued to prevent long-term sequelae.

Rhabdomyolysis caused by hypernatremia.

Rhabdomyolysis is a clinical picture which is rarely seen in children. In this case report here it is presented a patient who has biochemical and clinical signs of rhabdomyolysis and admitted to our clinic with hypernatremia. The authors think that it is necessary to be alert for rhabdomyolysis in severe hypernatremia cases.

Hashimoto's encephalopathy: four cases and review of literature

Hashimotos encephalopathy is a rare clinically heterogenous condition consisting of encephalopathy, seizures and variable neurological and psychiatric manifestations, accompanied by high titres of serum antithyroid antibodies. We described the clinical and laboratory findings of four children (aged 8–17 years) with Hashimotos encephalopathy. The clinical features of three patients at presentation included refractory epilepsy, and confusion, and one patient presented with behavioral and cognitive changes. During their presentation, two of them were in euthyroid, and the others were in hypothyroid status. All patients manifested increased antithyroid antibodies. Two patients improved with steroid treatment. The others responded to plasmapheresis instead of corticosteroid treatment. Physicians’ awareness of this complication is of great importance because most patients respond dramatically to the treatment.

Prognosis of Patients With Seizures Occurring in the First 2 Years

The aim of this study is to determine the prognosis of patients with seizure onset from 1 to 24 months of age in respect to epilepsy, developmental outcome, and neurological status. It also aims to determine predictive factors regarding an unfavorable prognosis. Seventy-five patients were retrospectively analyzed. Univariate analysis revealed the following findings: (1) mental retardation at initial admission, abnormal neurological finding, infantile spasm, use of more than 1 antiepileptic drug, epileptic activity on electroencephalography (EEG) of neonatal seizure, and perinatal anoxia were significant risk factors with regard to developmental outcome; (2) mental retardation at initial admission, abnormal neurological finding, infantile spasm, use of more than 1 antiepileptic drug, epileptic activity on EEG, symptomatic etiology, history of neonatal seizure, and perinatal anoxia were significant risk factors regarding neurological status; and (3) mental retardation at initial admission, neurological abnormality, infantile spasm, use of more than 1 antiepileptic drug, epileptic activity on EEG, status epilepticus, symptomatic etiology, seizure frequency of more than once per week, history of perinatal anoxia, and neonatal seizure were significant risk factors regarding epilepsy prognosis. In addition, multivariate analysis revealed that neurological abnormality and use of more than 1 antiepileptic drug were significant for developmental outcome, that epileptic activity on EEG and use of more than 1 antiepileptic drug were significant for neurological status, and that perinatal anoxia, infantile spasm, and status epilepticus were significant for epilepsy prognosis. These findings suggest that neurological abnormality, use of more than 1 antiepileptic drug, infantile spasm, status epilepticus, and perinatal anoxia are unfavorable predictive risk factors regarding the prognosis of patients with seizures that have an onset from 1 to 24 months of age.

Risk factors and treatment outcomes for children with arterial ischemic stroke

To investigate the risk factors and treatment outcomes for ischemic stroke in children, we reviewed the charts of 93 children with ischemic stroke seen at our hospital between 1997 and 2006. Age at stroke, sex, medical history, family history, clinical findings upon admission, history of seizure, and radiological findings were recorded. Mean age at onset of the initial stroke was 56.6+/-46.9 months, ranging from 1 month to 14 years. The male:female ratio was 1.6:1. Cardiac and infectious disease were the most common risk factors (37.7%). There were five children (5.4%) who had recurrent stroke and three (3.2%) who had multiple risk factors. Cardiac and infectious causes appeared to be the most important risk factors for ischemic stroke in children in the Adana region of Turkey.

Electroconvulsive therapy for refractory status epilepticus in a child: A case report.

1. McGrath A, Reid N, Boore J. Occupational stress in nursing. Int J Nurs Stud 2003;40:555-65. 2. Hughes RG, Rogers AE. Are you tired? Am J Nurs 2004;104:36-8. 3. Johnson CJ, Croghan E, Crawford J. The problem and management of sickness absence in the NHS: Considerations for nurse managers. J Nurs Manag 2003;11:336-42. 4. McVicar A. Workplace stress in nursing: A literature review. J Adv Nurs 2003;44:633-42. 5. Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: A new instrument for psychiatric practice and research. Psychiatry Res 1989;28: 193-213. 6. Johns MW. A new method for measuring daytime sleepiness: The Epworth Sleepiness Scale. Sleep 1991;14:540-5. 7. Short MA, Gradisar M, Lack LC, Wright HR. The impact of sleep on adolescent depressed mood, alertness and academic performance. J Adolesc 2013;36:1025-33. 8. Vanderlind WM, Beevers CG, Sherman SM, Trujillo LT, McGeary JE, Matthews MD, et al. Sleep and sadness: Exploring the relation among sleep, cognitive control, and depressive symptoms in young adults. Sleep Med 2014;15:144-9. 9. Sivertsen B, Lallukka T, Salo P, Pallesen S, Hysing M, Krokstad S, et al. Insomnia as a risk factor for ill health: Results from the large population-based prospective HUNT Study in Norway. J Sleep Res 2014;23:124-32. 10. Baldwin DC Jr, Daugherty SR. Sleep deprivation and fatigue in residency training: Results of a national survey of firstand second-year residents. Sleep 2004;27:217-23. 11. Landrigan CP, Rothschild JM, Cronin JW, Kaushal R, Burdick E, Katz JT, et al. Effect of reducing interns’ work hours on serious medical errors in intensive care units. N Engl J Med 2004;351:1838-48.

Multiple sulfatase deficiency: A case series of four children

Multiple sulfatase deficiency is biochemically characterized by the accumulation of sulfated lipids and acid mucopolysaccharides. The gene sulfatase-modifying factor 1 (SUMF1), recently identified, encodes the enzyme responsible for post-translational modification of a cysteine residue, which is essential for the activity of sulfatases. We describe clinical findings and mutation analysis of four patients. The patients presented with hypotonia, developmental delay, coarse face, ichthyosis, and hepatosplenomegaly. The diagnosis was made through clinical findings, enzymatic assays, and mutation analysis. We were detected to be homozygous for a novel missense mutation c. 739G > C causing a p.G247R amino acid substitution in the SUMF1 protein.

Factors Affecting Epilepsy Development and Epilepsy Prognosis in Cerebral Palsy

A study was conducted between November 2006 and October 2009 to determine the factors predicting the presence and prognosis of epilepsy in patients with cerebral palsy. We enrolled 2 groups of patients: 42 with cerebral palsy in group 1 and 56 patients with cerebral palsy and epilepsy in group 2. The subjects in group 2 were considered to have good epilepsy prognosis if they were free of seizures for the previous year; otherwise they were considered to have poor epilepsy prognosis. In group 2, neonatal epilepsy, family history of epilepsy, and moderate to severe mental retardation were significantly higher than in group 1 (P < 0.05). In univariate analysis, neonatal seizures, epileptic activity as measured by electroencephalography, and polytherapy were found to be predictors of poor epilepsy prognosis. Additionally, the need for long-term medication to control seizures unfavorably affects prognosis. In logistic regression analysis, neonatal seizure and interictal epileptic activity in electroencephalography were found to be independent predictors of poor epilepsy outcome. In addition, logistic regression analysis revealed that increasing age reduces the success of epilepsy treatment. Neonatal seizures, family history of epilepsy, and mental retardation were found to be important and independent predictors of development of epilepsy in patients with cerebral palsy.

Reversible posterior encephalopathy syndrome due to intravenous immunoglobulin in a child with Guillain-Barré syndrome

Reversible posterior leukoencephalopathy syndrome is characterized clinically by headache, abnormalities of mental status, and visual perception and seizures. We report a rare case of acute encephalopathy following intravenous immunoglobulin treatment for Guillain-Barré syndrome in whom posterior reversible encephalopathy syndrome developed without severe hypertension.