Maja Tomasović

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.

Complete trisomy 10p resulting from an extra stable telocentric chromosome.

This is a presentation of a child with a very rare trisomy of the chromosome 10 short arm (10p), due to centric fission of maternal chromosome 10. Conventional cytogenetics and fluorescence in situ hybridization (FISH) showed the child’s karyotype to be 47, XX, +fis(10)(p10)mat whereas the healthy maternal one was 47, XX, -10, +fis(10)(p10), +fis(10)(q10). This is the first clinical report of a child with a pure trisomy 10p as a result of the consequence of familial unequal transmission of telocentric chromosome with a fully functional centromere. In cases reported so far the trisomy 10p is accompanied with additional chromosome imbalances and that causes some of the phenotypic characteristics. However, the clinical features described in the current case are caused by pure trisomy 10p and, thus, delineate the 10p trisomy syndrome phenotype such as growth retardation, development delay, craniofacial dysmorphism, foot abnormalities and heart defect

P29 – 2665: Does positive genetic test help us to treat patient with Dravet syndrome?

Objective Severe myoclonic epilepsy (SMEI; Dravets syndrome) is a severe form of epilepsy which begins in infancy. The first seizures in Dravet syndrome are often prolonged febrile seizures, the course of Dravet syndrome is variable from one child to another. This may delay diagnosis for many months and often years after the onset of seizures. Most children with Dravet syndrome have a mutation in a gene called SCN1A. Methods We present the clinical, laboratory and neuroimaging data of our three SMEI patients, and the importance of genetic diagnosis to treatment decisions. Results First patient has first afebrile atonic episode when she has two months old, then multiple seizure types appeared, sometimes occurring in a daily cluster in spite of various antiepileptic combinations. Extensive neurometabolic and genetic findings including SCN1A gene revealed no abnormalities but due clinical criteria for Dravet syndrome, stiripentol was started with significant improvement in seizures control and development. Second patient presented his first episode of febrile seizures at eight months of age. In following years status epilepticus occurred monthly. At the age of 4 years, a missense mutation was found of the SCN1A gene and treatment with stiripentol was started, seizures stop, and his development is almost normal, but with behavioral disturbances. Third patient has various types of seizures provoked by a febrile state, noise and emotional stimuli. At the age of 12 months DNA diagnostics identified an SCN1A mutation, and then, after various combinations of medications treatment with stiripentol was started. The number of seizures was reduced and developmental delay is minimal. Conclusion The importance is that children with Dravet syndrome can have a genetic diagnosis before the full syndrome has evolved. This will reduce unnecessary diagnostic procedures, enable initiation of appropriate treatment, and thus achieve a better control of seizures and reduce neurological disability.

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.