The Impact of the IKBKG Gene on the Appearance of the Corpus Callosum Abnormalities in Incontinentia Pigmenti.

Incontinentia pigmenti (IP) is a rare skin disease combined with anomalies of the teeth, eyes, and central nervous system (CNS). Mutations of the IKBKG gene are responsible for IP. Among the most frequent CNS abnormalities found in IP using magnetic resonance imaging (MRI) are corpus callosum (CC) abnormalities. The aim of the study was to determine the presence of CC abnormalities, their relationship with the IKBKG mutations, and the possible presence of mutations of other genes. A group of seven IP patients was examined. Analyses of the IKBKG gene and the X-chromosome inactivation pattern were performed, as well as MRI and whole exome sequencing (WES) with the focus on the genes relevant for neurodegeneration. WES analysis showed IKBKG mutation in all examined patients. A patient who had a mutation of a gene other than IKBKG was excluded from further study. Four of the seven patients had clinically diagnosed CNS anomalies; two out of four had MRI-diagnosed CC anomalies. The simultaneous presence of IKBKG mutation and CC abnormalities and the absence of other mutations indicate that IKBKG may be the cause of CC abnormalities and should be included in the list of genes responsible for CC abnormalities.

Central nervous system involvement in hemophagocytic lymphohistiocytosis: a single-center experience.

BACKGROUND: Hemophagocytic lymphohistiocytosis is a rare multisystem disorder characterized by proliferation and diffuse infiltration multiple organs with histiocytes, including the central nervous system. PATIENTS AND METHODS: Thirty children diagnosed with hemophagocytic lymphohistiocytosis between 1997 and 2010 were reviewed and analyzed. Central nervous system disease involvement was defined as the presence of neurological symptoms and signs or elevated values of cerebrospinal fluid cells and/or proteins. RESULTS: Among the 30 patients, 17 (56%) had central nervous system involvement. Fourteen patients (46%) presented with neurological symptoms including seizures, irritability, bulging fontanelle, cranial nerve palsy, or disturbance of consciousness, whereas the remaining three patients developed central nervous system symptoms during the course of the disease. Seventeen patients (56%) had cerebrospinal fluid abnormalities. Neuroradiological studies were performed in nine patients. The most common findings were edema, atrophy, subcortical necrosis, and high signal intensity on T2-weighted magnetic resonance imaging. All patients were treated according to the Hemophagocytic Lymphohistiocytosis-94 and Hemophagocytic Lymphohistiocytosis-2004 protocols. Patients with central nervous system involvement had greater mortality. In prediction of the outcome, the cutoff value for cerebrospinal fluid protein was 470 mg/L. The most common neurological sequela was psychomotor delay. CONCLUSION: Central nervous system involvement in hemophagocytic lymphohistiocytosis is common and is associated with poor outcome.

[Adams-Oliver syndrome: case report].

INTRODUCTION: Adams-Oliver syndrome is characterized by congenital aplasia of the vertex skin of the skull in combination with skull and transverse limb defects. CASE OUTLINE: We presented a 5-month old female infant with Adams-Oliver syndrome manifested as cutis marmorata, dilated scalp veins and limb reduction defects. Clinical manifestation also included thumb hypoplasia and extreme hypoplasia of other fingers, with agenesis of all toes on both feet. Echocardiogram revealed foramen ovale apertum. Venography showed dilated malformed scalp and neck veins, predominantly on the right side. On the basis of the clinical features and extended investigation we confirmed Adams-Oliver syndrome in the presented patient. CONCLUSION: We recommended prenatal diagnosis in case of future pregnancies, ultrasound examination, and follow-up of foetal anomalies.

Clinical characteristics of respiratory syncytial virus infection in neonates and young infants.

INTRODUCTION/AIM: Infection with respiratory syncytial virus (RSV) occurs during the first year of life in 50% of children and 20%-40% of them have signs of lower respiratory tract infection (bronchiolitis or pneumonia). There is an increased risk for complicated course and death from RSV infection in premature infants, especially those with bronchopulmonary dysplasia (BPD) or congenital heart disease. The aim of our study was to analyze clinical characteristics of laboratory confirmed RSV infection in order to evaluate the need for preventive measures in neonates and young infants. METHODS: The prospective study included children under age of 12 months admitted to our hospital in the period November 2008-March 2009 who were positive for RSV by enzyme immunoassay membrane test. The course of disease was assessed by clinical score and radiographic findings. RESULTS: Infection with RSV was confirmed in 91 patients: 21 (23.0%) were under the age of 30 days, 37 (40.7%) were between 31-60 days, and 33 patients (36.3%) were older than 60 days (p > 0.05). The highest hospitalization rate was in January--33 patients (36.3%; p < 0.01). Disease severity score in these age groups (AG) were: 8.4 +/- 0.4 (AG 0-30 days); 9.0 +/- 0.3 (AG 31-60 days) and 8.3 +/- 0.3 (AG > 60 days), without statistically significant difference among the groups (p > 0.05). Clinical scores in patients with and without risk factors were 10.5 +/- 0.5 and 8.3 +/- 0.2, respectively (p < 0.01). Pathological radiographic findings were observed in 72 (79.1%) and complications (apnea, significant atelectasis, encephalopathy) occured in 15 (16.5%) patients. The average length of hospital stay in complicated and uncomplicated course of the disease was 9 days and 6 days, respectively (p < 0.01). Therapy in 85 (93.4%) patients included bronchodilators, while systemic glucocorticoids and oxygen therapy were used in 51 (56.0%) and 44 (48.4%) patients, respectively. Death occured in 2 (2.2%) patients, both from a high risk group (the patient with BPD and the other one with congenital heart disease and Down syndrome). CONCLUSION: Infection with RSV in our settings showed marked seasonal characteristics with highest hospitalization rate in January. Although the course and outcome of the disease were favorable in the majority of our patients, the need for hospitalization and administration of therapy with possible side effects warrants that general measures for prevention of respiratory infections are followed especially in the first year of life. Severe disease and death are more probable in neonates and infants with risk factors. In these children passive immunisation with specific monoclonal antibody (e.g. palivizumab) during RSV season should be considered.

Coagulation disturbances in paediatric patients with hepatic veno-occlusive disease after stem cells transplantation.

INTRODUCTION: Hepatic veno-occlusive disease (VOD) is a life threatening complication after stem cells transplantation (SCT). Its prediction, precise diagnosis and treatment remain unclear. OBJECTIVE: Our goals were to determine the incidence, outcome and changes in haemostatic parameters in patients with VOD. Also, we tried to determine coagulation disturbances and their practical significance in early diagnosis of such patients. METHODS: We prospectively evaluated all consecutive VOD patients after SCT, aged 3 months to 17 years, from February 2004 to July 2008 treated at the Mother and Child Health Institute of Serbia "Dr Vukan Cupic" (IMD). All patients were diagnosed according to the Seattle criteria. The values of PT, aPTT, fibrinogen, FVIII, AT and vWF were measured on the day prior to the initiation of conditioning regiment and on the days 1, 7 and 14 from the moment of VOD diagnosis. Laboratory testing was performed in the IMD haemostasis laboratory and results were statistically evaluated. RESULTS: During the study period 74 SCT were performed at IMD. VOD developed 11 patients; 10 of 46 were autologous and 1 of 28 allogeneic SCT patients. In our group of patients the incidence of VOD was 14.8%. VOD was classified as mild in 7, moderate in 1 and severe in 3 patients. At the moment of establishing the diagnosis all patients had a significantly increased activity of vWF, FVIII and fibrinogen, and decreased AT. All of them were dependent on platelet transfusions. CONCLUSION: Platelet transfusion dependence suggests coagulation activation with great significance and indicates a possible development of VOD. Our results also suggest that monitoring coagulation parameters levels in the first five days from the establishment of diagnosis may have a significant predictive value for VOD outcome.