Baris Malbora

Epilepsy in Mowat-Wilson syndrome: delineation of the electroclinical phenotype.

Mowat–Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene and is characterized by distinctive facial features, epilepsy, moderate to severe intellectual disability, corpus callosum abnormalities and other congenital malformations. Epilepsy is considered a main manifestation of the syndrome, with a prevalence of about 70–75%. In order to delineate the electroclinical phenotype of epilepsy in MWS, we investigated epilepsy onset and evolution, including seizure types, EEG features, and response to anti‐epileptic therapies in 22 patients with genetically confirmed MWS. Onset of seizures occurred at a median age of 14.5 months (range: 1–108 months). The main seizure types were focal and atypical absence seizures. In all patients the first seizure was a focal seizure, often precipitated by fever. The semiology was variable, including hypomotor, versive, or focal clonic manifestations; frequency ranged from daily to sporadic. Focal seizures were more frequent during drowsiness and sleep. In 13 patients, atypical absence seizures appeared later in the course of the disease, usually after the age of 4 years. Epilepsy was usually quite difficult to treat: seizure freedom was achieved in nine out of the 20 treated patients. At epilepsy onset, the EEGs were normal or showed only mild slowing of background activity. During follow‐up, irregular, diffuse frontally dominant and occasionally asymmetric spike and waves discharges were seen in most patients. Sleep markedly activated these abnormalities, resulting in continuous or near‐to‐continuous spike and wave activity during slow wave sleep. Slowing of background activity and poverty of physiological sleep features were seen in most patients. Our data suggest that a distinct electroclinical phenotype, characterized by focal and atypical absence seizures, often preceded by febrile seizures, and age‐dependent EEG changes, can be recognized in most patients with MWS.

Successful Use of Recombinant Factor VIIa (NovoSeven®) During Cardiac Surgery in a Pediatric Patient with Congenital Factor XI Deficiency

We report our experience with the use of recombinant activated factor VII (rFVIIa) during cardiac surgery in a 4.5-year-old boy with severe congenital FXI deficiency and a congenital heart disease. After weaning the patient from cardiopulmonary bypass, the first intravenous dose of rFVIIa (90 μg/kg) was administered. This same dosage was repeated eight more times, at 2- to 4-hour intervals postoperatively. There was no bleeding during and after surgery. rFVIIa treatment may be used successfully in children with severe FXI deficiency in major operations such as open heart surgery.

CHARGE-like presentation, craniosynostosis and mild Mowat-Wilson Syndrome diagnosed by recognition of the distinctive facial gestalt in a cohort of 28 new cases.

Mowat–Wilson syndrome (MWS) is characterized by moderate to severe intellectual disability and distinctive facial features in association with variable structural congenital anomalies/clinical features including congenital heart disease, Hirschsprung disease, hypospadias, agenesis of the corpus callosum, short stature, epilepsy, and microcephaly. Less common clinical features include ocular anomalies, craniosynostosis, mild intellectual disability, and choanal atresia. These cases may be more difficult to diagnose. In this report, we add 28 MWS patients with molecular confirmation of ZEB2 mutation, including seven with an uncommon presenting feature. Among the “unusual” patients, two patients had clinical features of charge syndrome including choanal atresia, coloboma, cardiac defects, genitourinary anomaly (1/2), and severe intellectual disability; two patients had craniosynostosis; and three patients had mild intellectual disability. Sixteen patients have previously‐unreported mutations in ZEB2. Genotype‐phenotype correlations were suggested in those with mild intellectual disability (two had a novel missense mutation in ZEB2, one with novel splice site mutation). This report increases the number of reported patients with MWS with unusual features, and is the first report of MWS in children previously thought to have CHARGE syndrome. These patients highlight the importance of facial gestalt in the accurate identification of MWS when less common features are present.

Incidence of and risk factors for childhood thrombosis: a single-center experience in Ankara, Turkey.

This study was conducted to analyze the incidence of and risk for thrombosis in thrombotic children monitored in the Department of Pediatric Hematology of our hospital at the time of diagnosis, in addition to the clinical characteristics of those patients. The clinical and laboratory findings of 122 patients diagnosed with thrombosis from 1997 to 2006 were retrospectively analyzed. The incidence of thrombosis was 88.6/10,000 hospital admissions. The authors found that 31.1% of the patients studied had a thrombosis in more than 1 region. The incidence of thrombosis by anatomic site was as follows: 42 thromboses in the peripheral arterial system, 39 in an intracardiac region, 38 in the abdominal venous system, 36 in the deep peripheral venous system, and 28 in the cerebral vascular system. The mean age of the patients at the time of diagnosis was 4.9 years. Of the patients studied, 10.7% were neonates, 35.3% were infants younger than 1 year, and 48.4% were younger than 2 years. Most of the patients had a congenital cardiac disease and spontaneous thrombosis, and 66.1% had at least 1 acquired risk factor, the most common of which were having undergone surgery (42%) or wearing a central venous catheter (39%). A hereditary factor for the development of thrombosis was present in 54% of the patients. The most frequently observed hereditary risk factor was the MTHFR 677C-T mutation, and the second most common was the factor V Leiden mutation. Thrombosis should be considered a systemic disorder, and thrombotic patients should be evaluated with appropriate methods. Acquired and hereditary risk factors should be analyzed systematically in thrombotic patients.

Delayed recognition of intrathecal methotrexate overdose.

A 10-year-old girl who presented to our hospital was diagnosed as having B-precursor cell acute lymphoblastic leukemia. St Judes Total XIII protocol was started. In the second block of the consolidation phase, 10 hours after triple intrathecal treatment, we realized that instead of 12 mg, 120 mg of methotrexate had accidentally been given. Although the patient had no symptoms 10 hours after intrathecal treatment, to prevent the possible neurotoxic effects of methotrexate, a cerebrospinal fluid exchange was performed. Simultaneously, systemic dexamethasone and calcium folinic acid were given. At the time of this writing (2 y), the patient has had no symptoms and has continued on the chemotherapy protocol as planned. Administration of high-dose intrathecal methotrexate may not lead to symptoms, as was the case in our patient. This may be related to individual variations in cerebrospinal fluid dynamics and drug metabolism.

Severe adenovirus infection associated with hemophagocytic lymphohistiocytosis.

Ferda Özbay Hoşnut1, Figen Özçay1, Barış Malbora2, Şamil Hızlı3, namık Özbek4 1Başkent University Faculty of Medicine, Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Ankara, Turkey 2Dr. Sami Ulus Research and Training Hospital of Women’s and Children’s Health and Diseases, Ankara, Turkey 3Dr. Sami Ulus Research and Training Hospital of Women’s and Children’s Health and Diseases, Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Ankara, Turkey 4Başkent University Faculty of Medicine, Department of Pediatric Hematology, Ankara, Turkey

Posterior reversible leukoencephalopathy syndrome in children with hematologic disorders

OBJECTIVE Posterior reversible leukoencephalopathy syndrome (PRES) is characterized by headache, altered mental status, cortical blindness, and seizures associated with neuroradiological findings. It involves predominantly white matter of the parieto-occipital lobes. Several medications and disorders play a role in the etiology of PRES. In this study, we aimed to show how the prognosis of PRES in hematological diseases of childhood might be according to the etiological factors. METHODS Here, we report PRES in six patients, aged 4 to 14 years, with diagnoses of leukemia and aplastic anemia. RESULTS Suggested causes in our patients were chemotherapeutics, hypertension, infection and antimicrobial drug administration, tumor lysis syndrome, acute renal failure and hemodialysis, immunosuppressive drug administration, and hypomagnesemia. One of the patients died of sepsis, renal failure and pulmonary hemorrhage and another died of relapse after total recovery from PRES. The other four patients are under follow-up without problems. CONCLUSION We suggest that PRES can recover fully with early diagnosis and treatment whereas it can show poor prognosis depending on the etiology.

Lupus Anticoagulant Positivity in Pediatric Patients With Prolonged Activated Partial Thromboplastin Time: A Single-Center Experience and Review of Literature

The presence of lupus anticoagulants (LAs) is an important cause of activated partial thromboplastin time (aPTT) prolongation found in children after an infection or during screening tests before surgical intervention. The authors retrospectively reviewed the charts of 68 patients who have been consulted from surgery departments with prolonged aPTT. These patients were reevaluated with aPTT analysis after 1 week. Thirteen patients had normal aPTTs. Therefore, 55 patients remained with prolonged aPTTs. LA positivity was detected in 39 patients. Sixteen of these had prolonged aPTT prior to surgery (41%). Others with LA positivity had systemic lupus erythematosus (SLE; n = 6), infection (n = 5), leukemia (n = 3), hemolytic uremic syndrome (n = 2), epistaxis (n = 2), antiphospholipid syndrome (APS; n = 1), chronic immune thrombocytopenic purpura (n = 1), acute poststreptococcal glomerulonephritis (n = 1), central nervous system (CNS) thrombosis (n = 1), and congenital heart disease (n = 1). None of the patients had bleeding history. LA positivity rarely leads to bleeding and/or thrombosis. Specific therapy is usually not needed. Further prospective multicenter studies are required to understand clinical outcomes and laboratory correlation in children with positive LA.

CARDIAC INVOLVEMENT IN AN ADOLESCENT WITH ACUTE LYMPHOBLASTIC LEUKEMIA

Cardiac complications of the pediatric patients with acute leukemia are common. Most of the cardiac complications may be due to chemotherapeutics such as antracyclins, besides anemia, infections, or direct leukemic infiltrations of the heart. It is reported that leukemic infiltration is frequent in the postmortem examination of the myocardium and pericardium. However, at the antemortem examination, pericardial involvement is rare and there is no myocardial involvement reported at the time of diagnosis in patients with acute leukemia in the English literature. Here, the authors report an adolescent with acute lymphoblastic leukemia who had myocardial infiltration at the time of diagnosis.

Ophthalmologic Findings in Children with Leukemia: A Single-Center Study

Objectives: Ophthalmologic disease in patients with acute leukemia occurs due to primary leukemic infiltration (involvement), or secondary to the disease and its treatment. In recent years the life expectancy of acute leukemia patients has increased with the advent of modern therapies. The present study aimed to determine the incidence of ocular manifestations in children with acute leukemia. Materials and Methods: The study included 120 patients diagnosed with acute leukemia at Başkent University Hospital, Pediatric Hematology Department between 1995 and 2010. All the patients were examined by an ophthalmologist via direct and indirect ophthalmoscopy. Results: Among the patients, 83 (69.2%) were diagnosed with acute lymphoblastic leukemia, 35 (29.1%) with acute myeloblastic leukemia, and 2 (1.7%) with mixed-lineage leukemia. In all, 58 ophthalmic manifestations were noted in 41 patients (34.2%). In our patients, 12 ophthalmologic involvements were present at admission and 46 ocular findings occurred during follow-up. The incidence of these manifestations increased with age. Conclusion: Ophthalmologic manifestations were not correlated with gender, hematological parameters at disease onset, type of leukemia, or the frequency of relapse and survival. To more clearly determine the effect of ophthalmologic manifestations on the prognosis of leukemia, larger scale and multi-center studies are needed.