Biserka Rešić

Platelet Function Analysis in Children with Schönlein-Henoch Syndrome

BACKGROUND Schönlein-Henoch syndrome (SHS) or anaphylactic purpura in childhood is the result of pathologic and immunologic responses to different antigens. These antigens could induce the formation of immune complexes responsible for vasculitis and their precipitation on the endothelium of small blood vessels. Purpuric bruises, hematuria, hematemesis, melena, or hematochesis may suggest coagulation disturbances. Increasing bleeding tendency may suggest platelet function disturbance. To examine the qualitative function of platelets in children with SHS, we decided to analyze its aggregation function. METHODS Using the Born method of testing, we analyzed platelet aggregation in 24 children with SHS. RESULTS Based on the aggregograms examined, we observed that most patients had abnormal aggregation curves, in which platelets demonstrated a block of release of the endogenous ADP, with or without disaggregation. CONCLUSIONS One clinical symptom of SHS appearing in most patients is a mild or increased tendency toward bleeding. On measuring induced aggregation of platelets in children with SHS, we observed that the qualitative function of platelets was disturbed.

Clinical sensitivity and specificity of multiple T2-hyperintensities on brain magnetic resonance imaging in diagnosis of neurofibromatosis type 1 in children: diagnostic accuracy study

Aim To determine the prevalence, number, and location of multiple (≥2) T2-hyperintensities on brain magnetic resonance imaging (MRI) in children with neurofibromatosis type 1 (NF1) and their correlation with age, and to establish their sensitivity, specificity, and accuracy for the diagnosis of NF1 in children, especially in the early age (2-7 years). Methods We performed a cross-sectional study of 162 patients with NF1 from Croatian Neurofibromatosis Association Database and 163 control children between the ages of 2 and 18 years who underwent brain MRI between 1989 and 2009. Results Multiple T2-hyperintensities were present in 74% of NF1 patients and 1.8% of controls. They were mainly located in the basal ganglia, brainstem, and cerebellum and were significantly decreased in prevalence and number in the older age. T2-hyperintensities had excellent diagnostic accuracy with the area under the receiver operating characteristic (ROC) curve of 0.849 and 95% confidence interval (CI) of 0.805-0.886. The diagnostic sensitivity, specificity, and accuracy rate of T2-hyperintensities for NF1 were highest in the youngest age (2-7 years): 81% (95% CI 71%-89.1%), 99% (95% CI 92.3%-100%), and 85.8 (95% CI 83.3-93.8), respectively. Conclusion This study strongly suggests the inclusion of T2-hyperintensities on brain MRI on the list of diagnostic criteria for NF1, especially in children of early age, when the clinical penetration of the NF1 gene has not yet been completely finished.

Association of NOS3 tag polymorphisms with hypoxic-ischemic encephalopathy

Aim To test the association of NOS3 gene with hypoxic-ischemic encephalopathy (HIE). Methods The study included 110 unrelated term or preterm born children (69 boys and 41 girls) with HIE and 128 term and preterm born children (60 boys and 68 girls) without any neurological problems after the second year of life. Children with perinatal HIE fulfilled the diagnostic criteria for perinatal asphyxia. All children were admitted to the Clinical Hospital Split between 1992 and 2008. We analyzed 6 tagging single nucleotide polymorphisms (SNP) within NOS3 gene (rs3918186, rs3918188, rs1800783, rs1808593, rs3918227, rs1799983), in addition to previously confirmed NOS3-associated SNP rs1800779. Genotyping was conducted using real-time polymerase chain reaction (PCR). Association analyses were performed according to allelic and genotypic distribution. Results Allelic test did not show any SNP association with HIE. SNP rs1808593 showed genotype association (P = 0.008) and rs1800783-rs1800779 TG haplotype showed an association with HIE (P < 0.001). The study had 80% statistical power to detect (α = 0.05) an effect with odds ratio (OR) = 2.07 for rs3918186, OR = 1.69 for rs3918188, OR = 1.70 for rs1800783, OR = 1.80 for rs1808593, OR = 2.10 for rs3918227, OR = 1.68 for rs1800779, and OR = 1.76 for rs1799983, assuming an additive model. Conclusion Despite the limited number of HIE patients, we observed genotypic and haplotype associations of NOS3 polymorphisms with HIE.

Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.

The MECP2 gene mutation screening in rett syndrome patients from Croatia

Abstract:  Rett syndrome (RTT) is an X‐linked dominant neurodevelopmental disorder almost exclusively affecting females and is usually sporadic. Mutations in MECP2 gene have been found in more than 80% of females with typical features of RTT. In this study, we analyzed 15 sporadic cases of RTT. In 7 of 15 patients (47%), we detected pathogenic mutations in the coding parts of MECP2 fourth exon. We found two missense (T158M, R133C), two nonsense (R168X, R270X), two frameshift mutations (P217fs and a double deletion of 28‐bp at 1132–1159 and 10‐bp at 1167–1176), and one in‐frame deletion (L383_E392del10). To our knowledge, the last two mutations have not been reported yet. We also detected one previously described polymorphism (S194S). In conclusion, these results show that the fourth exon should be the first one analyzed because it harbors most of the known mutations. Moreover, mutation‐negative cases should be further analyzed for gross rearrangements. This is the first study of its kind in Croatia and it enabled us to give the patients an early confirmation of RTT diagnosis.

Sleep EEG Composition in the First Three Months of Life in Monozygotic and Dizygotic Twins

We investigated genetic influence on sleep electroencephalogram (EEG) composition by a classical twin study of monozygotic (MZ) and dizygotic (DZ) twins in the first 3 months of life. Polysomnographic (PSG) recordings were obtained in 10 MZ and 20 DZ twin pairs in the 37th, 46th, and 52nd week of postmenstrual age (PMA). The EEG power spectra were generated on the basis of fast Fourier transformation (FFT). Genetic influence on active sleep/rapid eye movement (AS/REM)] and quiet sleep/ non rapid eye movement (QS/NREM) sleep composition was estimated by calculating within pair concordance and the intraclass correlation coefficients (ICCs) for delta (0.5-3.5 Hz), theta (4-7.5 Hz), alpha (8-11.5 Hz), sigma (12-14 Hz), and beta (14.5-20 Hz) at central derivation. MZ twins show higher ICCs than DZ twins for alpha, sigma, and beta spectral powers during QS/NREM sleep in the 37th, 46th, and 52nd week PMA. However, there was no significant difference (P > .05) between the 2 types of twins in absolute differences of EEG spectral power of the alpha, beta, and sigma frequency ranges in the 37th, 46th, and 52nd week PMA. The greatest mean absolute difference within MZ and DZ twin pairs and also between MZ and DZ twin groups was identified in the delta frequency range. Our findings gave an indication of genetic influence on alpha, sigma, and beta frequency ranges in the QS/NREM sleep stage.

Diagnosis and follow up in three cases of incontinentia pigmenti

Incontinentia pigmenti (IP) is an X-linked dominant genodermatosis characterized by abnormalities of the tissue and organs derived from the ectoderm and neuroectoderm. Involvement of the skin, teeth, hair, and nails is seen in conjunction with neurologic and ophtalmologic anomalies. The prognosis depends on the presence and severity of associated extracutaneous manifestations. Morbidity and mortality primarily result from neurologic and ophtalmologic complications, including mental retardation, seizures, and vision loss. In this report, three patients at different stages of the disease are presented. Diagnosis and the course of the disease are discussed.