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P105 – 2378: Microcephaly, pontocerebellar hypoplasia and epilepsy in patients with CASK mutations
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EUROPEAN JOURNAL O F PAEDIATRIC NEUROLOGY
P105 - 2378 Microcephaly, pontocerebellar hypoplasia and epilepsy in patients with CASK mutations A. Máté, K. Szakszon, A.J. Nagy, M. Zombor, G. Rudas, A. Zimmermann, F. van Ruissen, F. Baas, L. Sztriha. Department of Neurosurgery, University of Szeged, Szeged, Hungary Objective: The CASK protein is a member of the membraneassociated guanylate kinase protein family, and plays a role in neural development and synaptic function. The CASK gene is located on the X-chromosome, its loss-of-function mutations have been shown to cause microcephaly and pontine and cerebellar hypoplasia (MIC-PCH) in females. We report the cases of two girls with MIC-PCH caused by different de novo loss-of function mutations of the CASK gene. Methods: Clinical evaluation included neurological examination, developmental assessment, brain MRI, EEG, laboratory tests, audiologic and ophthalmologic examinations, and genetic testing. Sequence analysis of the entire coding region (exons 1–27), and all intron-exon boundaries of the CASK gene was carried out. Results: Both patients presented with congenital microcephaly, intellectual disability, delayed motor development in association with therapy-resistant epilepsy beginning around 2 years of age. Brain MRI revealed hypoplasia of the brainstem and cerebellum and the EEG showed bilateral periodic spike-and-wave discharges in both girls. One of them had a very severe phenotype with spastic tetraplegia, visual impairment and hearing loss, while the other patient was able to achieve some motor milestones like rolling and sitting with support. Pathogenic heterozygous deletions in the CASK gene were identified in both girls: deletion of 8 nucleotides (c.20_27delTGTTCGAG p.Leu7ArgfsX35) in one of them and deletion of a single nucleotide (c.1034delG p.Arg345Lysfs*) in the other one. Both deletions result in a frameshift leading to the formation of a premature stop codon. The parents are healthy. Conclusion: Mutations of the CASK gene should be considered in female patients with microcephaly, intellectual disability and pontocerebellar hypoplasia. These girls are sporadic cases with de novo mutations. Identification of CASK mutations enables accurate and reassuring genetic counselling.
P106 - 2381 The role of videomonitoring in the study of features of bioelectrical activity in children with delay in both mental and speech development R. Kenzhegulova, A. Jaxybayeva, L. Tekebayeva. National Research Cenetr for Mother and Child Health Objective: The study is to analyze the specific characteristics of the brain bioelectrical activity in children with delay in both mental and speech development. Methods: We have examined 52 children with severe delay in both mental and speech development. The children were in the department of neurology from 2011 to 2014. They were from 8 months to 5 years of age. Children with epilepsy bouts and motor disorders were not included in the study. The device , Russian Federation, Ivanovo, was used for the study. Clinically, the children manifested based on their age in the following manner: 8–9 months of age – no babbling (repetition of identical syllables; 1 year of age – very silent baby, almost no voicing; 18 months of age – no simple words such as “mommy”, “give”, and no comprehension of these words; 2–3 years of age – knowledge and usage of a very small set of words, no repetition of new words spoken by others; 4–5 years of age – no ability to make up sentences, no comprehension of simple stories told by adults. Results: The findings of EEG test performed on children with delay in both mental and speech development are as follows: 1. Prolonged generalized or diffuse epileptic activity, in 10 children, 19.23%; 2. Prolonged and periodic slowdown in frontal, frontocentral, and frontotemporal
19s (2015) S1 – S152
leads, in 21 children, 40.38%; 3. Slowdown and disorganization in the background activity, in 13 children, 25%; 4. Disorganized pathologic EEG pattern, absence of physiologic sleep and wake patterns alongside with diffuse bursts of theta and delta waves, in 8 children, 15.38%. Conclusion: The information concerning the brain function, which was obtained by registering of the bioelectric activity, makes it easier to diagnose the changes in development, and identification the possible opportunities to conduct an adequate individualized correction.
P107 - 2404 Familial aggregation and phenotypic differences in a follow up study of SLI children I. Triltsch-Ciurea, G. Schädler. Josefinum, Department of Neuropediatrics, Augsburg, Bayern Objective: SLI (Specific Language Impairment) is a disorder of language acquisition accompanied by otherwise normally developing child. In this study we have characterized 61 children with SLI (with the focus on the correlation between phenotype and positive family history) considering age-dependent changes of phenotype in the course of development. Methods: We collected phenotypic information from a homogeneous sample of 61 children (with normal non-verbal abilities) that were first examined between 3 and 3.6 years because of very restricted vocabulary and no or very simple 2–3 word-utterances. We re-assessed them periodically at the average age of 4, 5 and 6 years. Personal and family – history was recorded, a nonverbal intelligence test was performed (SON-R). Expressive and receptive vocabulary, grammar and phonology were measured periodically. Results: A positive family history (FH+) for SLI 39%, for dyslexia 22%, both 17% was found for German children and 44% SLI, 21% dyslexia and 12% both for bilingual children. The phenotype of SLI changed over time. The most frequent syndrome was found at the age of 4 (74%): severe language impairment (morphology + syntax) with severe or moderate phonological difficulties was still high at the age of 5 (57%) and dropped at the age of 6 (26% German; 35% bilingual children) despite of early and continuous therapy. This syndrome had the highest frequency of FH+ (65% for SLI and 33% for dyslexia). Children with poor outcome (26% German; 35% bilingual) had statistically significant higher FH+ too. Conclusion: The observed familiarity, the relative slow therapy-response and the non-linear course of development support the assumption of genetic factors in the cause of SLI phenotype. The course of development seems to follow a deviant maturational genetic programme.
P108 - 2408 Use of the cranial computed tomography in children with acute neurological complaints at the Pediatric Emergency Department B. Kaya, K. Aydin, O. Derinoz. Department of Pediatrics, University of Gazi, Ankara, Turkey Objective: The objective of this study is to determine the prevalance, indications, aid to the diagnosis and the treatment and the excessive and irrelevant use of the cranial computed tomography (CCT) in children with acute neurological complaints. Methods: The records of the patients, who presented to Pediatric Emergency Department of Gazi University Medical Faculty between June 2012 to June 2013 with acute neurological complaints and had CCT, were reviewed retrospectively. Results: During one year, 34.575 patients were admitted to our emergency department. Ranging in age from one month to eighteen years, 146 girls and 240 boys, 460 had CCT scan, 386 patients were included. The indications for CCT are trauma 78.4%, seizure 6.9%, unconsciousness 4.1%, headache 3.1% and the others 7.2% respectively. The results of CCT scans of 156 40.4% were reported
EUROPEAN JOURNAL O F PAEDIATRIC NEUROLOGY
P105 - 2378 Microcephaly, pontocerebellar hypoplasia and epilepsy in patients with CASK mutations A. Máté, K. Szakszon, A.J. Nagy, M. Zombor, G. Rudas, A. Zimmermann, F. van Ruissen, F. Baas, L. Sztriha. Department of Neurosurgery, University of Szeged, Szeged, Hungary Objective: The CASK protein is a member of the membraneassociated guanylate kinase protein family, and plays a role in neural development and synaptic function. The CASK gene is located on the X-chromosome, its loss-of-function mutations have been shown to cause microcephaly and pontine and cerebellar hypoplasia (MIC-PCH) in females. We report the cases of two girls with MIC-PCH caused by different de novo loss-of function mutations of the CASK gene. Methods: Clinical evaluation included neurological examination, developmental assessment, brain MRI, EEG, laboratory tests, audiologic and ophthalmologic examinations, and genetic testing. Sequence analysis of the entire coding region (exons 1–27), and all intron-exon boundaries of the CASK gene was carried out. Results: Both patients presented with congenital microcephaly, intellectual disability, delayed motor development in association with therapy-resistant epilepsy beginning around 2 years of age. Brain MRI revealed hypoplasia of the brainstem and cerebellum and the EEG showed bilateral periodic spike-and-wave discharges in both girls. One of them had a very severe phenotype with spastic tetraplegia, visual impairment and hearing loss, while the other patient was able to achieve some motor milestones like rolling and sitting with support. Pathogenic heterozygous deletions in the CASK gene were identified in both girls: deletion of 8 nucleotides (c.20_27delTGTTCGAG p.Leu7ArgfsX35) in one of them and deletion of a single nucleotide (c.1034delG p.Arg345Lysfs*) in the other one. Both deletions result in a frameshift leading to the formation of a premature stop codon. The parents are healthy. Conclusion: Mutations of the CASK gene should be considered in female patients with microcephaly, intellectual disability and pontocerebellar hypoplasia. These girls are sporadic cases with de novo mutations. Identification of CASK mutations enables accurate and reassuring genetic counselling.
P106 - 2381 The role of videomonitoring in the study of features of bioelectrical activity in children with delay in both mental and speech development R. Kenzhegulova, A. Jaxybayeva, L. Tekebayeva. National Research Cenetr for Mother and Child Health Objective: The study is to analyze the specific characteristics of the brain bioelectrical activity in children with delay in both mental and speech development. Methods: We have examined 52 children with severe delay in both mental and speech development. The children were in the department of neurology from 2011 to 2014. They were from 8 months to 5 years of age. Children with epilepsy bouts and motor disorders were not included in the study. The device , Russian Federation, Ivanovo, was used for the study. Clinically, the children manifested based on their age in the following manner: 8–9 months of age – no babbling (repetition of identical syllables; 1 year of age – very silent baby, almost no voicing; 18 months of age – no simple words such as “mommy”, “give”, and no comprehension of these words; 2–3 years of age – knowledge and usage of a very small set of words, no repetition of new words spoken by others; 4–5 years of age – no ability to make up sentences, no comprehension of simple stories told by adults. Results: The findings of EEG test performed on children with delay in both mental and speech development are as follows: 1. Prolonged generalized or diffuse epileptic activity, in 10 children, 19.23%; 2. Prolonged and periodic slowdown in frontal, frontocentral, and frontotemporal
19s (2015) S1 – S152
leads, in 21 children, 40.38%; 3. Slowdown and disorganization in the background activity, in 13 children, 25%; 4. Disorganized pathologic EEG pattern, absence of physiologic sleep and wake patterns alongside with diffuse bursts of theta and delta waves, in 8 children, 15.38%. Conclusion: The information concerning the brain function, which was obtained by registering of the bioelectric activity, makes it easier to diagnose the changes in development, and identification the possible opportunities to conduct an adequate individualized correction.
P107 - 2404 Familial aggregation and phenotypic differences in a follow up study of SLI children I. Triltsch-Ciurea, G. Schädler. Josefinum, Department of Neuropediatrics, Augsburg, Bayern Objective: SLI (Specific Language Impairment) is a disorder of language acquisition accompanied by otherwise normally developing child. In this study we have characterized 61 children with SLI (with the focus on the correlation between phenotype and positive family history) considering age-dependent changes of phenotype in the course of development. Methods: We collected phenotypic information from a homogeneous sample of 61 children (with normal non-verbal abilities) that were first examined between 3 and 3.6 years because of very restricted vocabulary and no or very simple 2–3 word-utterances. We re-assessed them periodically at the average age of 4, 5 and 6 years. Personal and family – history was recorded, a nonverbal intelligence test was performed (SON-R). Expressive and receptive vocabulary, grammar and phonology were measured periodically. Results: A positive family history (FH+) for SLI 39%, for dyslexia 22%, both 17% was found for German children and 44% SLI, 21% dyslexia and 12% both for bilingual children. The phenotype of SLI changed over time. The most frequent syndrome was found at the age of 4 (74%): severe language impairment (morphology + syntax) with severe or moderate phonological difficulties was still high at the age of 5 (57%) and dropped at the age of 6 (26% German; 35% bilingual children) despite of early and continuous therapy. This syndrome had the highest frequency of FH+ (65% for SLI and 33% for dyslexia). Children with poor outcome (26% German; 35% bilingual) had statistically significant higher FH+ too. Conclusion: The observed familiarity, the relative slow therapy-response and the non-linear course of development support the assumption of genetic factors in the cause of SLI phenotype. The course of development seems to follow a deviant maturational genetic programme.
P108 - 2408 Use of the cranial computed tomography in children with acute neurological complaints at the Pediatric Emergency Department B. Kaya, K. Aydin, O. Derinoz. Department of Pediatrics, University of Gazi, Ankara, Turkey Objective: The objective of this study is to determine the prevalance, indications, aid to the diagnosis and the treatment and the excessive and irrelevant use of the cranial computed tomography (CCT) in children with acute neurological complaints. Methods: The records of the patients, who presented to Pediatric Emergency Department of Gazi University Medical Faculty between June 2012 to June 2013 with acute neurological complaints and had CCT, were reviewed retrospectively. Results: During one year, 34.575 patients were admitted to our emergency department. Ranging in age from one month to eighteen years, 146 girls and 240 boys, 460 had CCT scan, 386 patients were included. The indications for CCT are trauma 78.4%, seizure 6.9%, unconsciousness 4.1%, headache 3.1% and the others 7.2% respectively. The results of CCT scans of 156 40.4% were reported