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NOP06 Ataxia-Telangiectasia: two Bulgarian siblings with the 3576G>A founder mutation on ATM gene
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Abstracts: Poster Presentations, the Seventh European Paediatric Neurology Society (EPNS) Congress
pharmacoresistant generalized seizures of various types (tonic, clonic, tonic-clonic, atonic, myoclonic). Unfavourable seizure control was associated with developmental delay. EEGs showed bilateral spike and slow-wave abnormalities. Cerebellar symptoms, paraparesis, difficulties in walk and speech are his main deficits. No abnormalities on brain MRI scans were seen. Conclusion: Our case series confirm the heterogenecity in the clinical and neurophysiological features within the spectrum of hemimegalencephaly and KTWS. NOP06 Ataxia-Telangiectasia: two Bulgarian siblings with the 3576G>A founder mutation on ATM gene P. Dimova1 *, V. Bojinova1 , R. Varon-Mateeva2 , K. Sperling2 . 1 Clinic of Child Neurology, St. Naum University Hospital of Neurology, Sofia, Bulgaria, 2 Institute of Human Genetics, Charita´ Campus Virchow Clinic, Berlin, Germany We present two brothers with delayed diagnosis of ataxia-telangiectasia. Ataxia manifested at the age of 2 and 4 years, respectively. Conjunctival telangiectasia and cerebellar atrophy on brain computed tomography was obvious in both cases at the age of 6 years, while oculomotor and swallowing disturbances, and choreoatetotic movements developed one to two years later. Up to the manifestation of telangiectasia and due to the absence of alpha-fetoprotein elevation and immunoglobulin deficit other cerebellar disorders of childhood were suspected. At the age of purposeful genetic investigation signs of sensorimotor neuropathy and persistent hypoalbuminemia were also present. DNA examination of the siblings revealed a homozygosity for the point mutation 3576G>A on exon 26 of the ATM gene. This mutation leads to exon drop out and aberrant splicing. It has been found more frequently in south and south east Europe, therefore to have a founder effect. Described for the first time in Bulgarian patients, this mutation confirmed the diagnosis in our cases.
precludes conclusions about the presence of anterior horn cell loss in older patients, but we found no post mortem evidence of such loss in a 22 year-old female patient. NOP08 Aqueductal stenosis in the neurofibromatosis type 1 (NF1): presentation of 19 infantile patients I. Pascual-Castroviejo1 *, S.-I. Pascual-Pascual1 , R. VelazquezFragua1 , J. Viano ˜ 2 , F. Carceller3 . 1 Pediatric Neurology Service. University Hospital La Paz, Madrid, Spain, 2 Imagen Unit. Nuestra Sra del Rosario Clinic, Madrid, Spain, 3 Neurosurgery Service. University Hospital La Paz, Madrid, Spain Objective: To present a series of infantile patients with aqueductal stenosis associated with neurofibromatosis type 1 (NF1). Patients and methods: Nineteen patients with ages below 16 years, 11 girls and 8 boys, with NF1 presented hydrocephalus due to aqueductal stenosis. All patients, except one who died before the imagen study was performed and was diagnosed by autopsy, were studied by pneumoencephalography (since 1965 to 1974), computerized tomography (CT) (since 1975 to 1984), magnetic resonance (MR) or MR and CT (since 1985 to 2004) (two children had been studied by pneumoencephalography some years before) most times to discard optic pathway tumor and, in few patients, because of intracranial hypertension. Results: All patients showed threeventricular hydrocephalus with aqueductal stenosis. Eleven patients showed optic pathway tumor. One patient had a benign aqueductal tumor that impaired the normal flow of CSF. Neurological features of hydrocephalus occurred very rapidly in some patients and after several years of evolution in others. Conclusions: Aqueductal stenosis and hydrocephalus were identified at a short age because many patients were studied suspecting optic pathway tumor. Eleven patients (about 60%) associated optic pathway tumor and aqueductal stenosis.
NOP07 Neuromuscular abnormalities in ataxia telangiectasia; a clinical, electrophysiological and muscle ultrasound study
NOP09 Neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG). A series of 80 patients
M.M. Verhagen1 , N. van Alfen1 , M.A. Willemsen1 *, S. Pillen1 , J.-B.L. Yntema1 , J.A. Hiel2 , H. ter Laak1 , M. van Deuren1 , C.M. Weemaes1 . 1 Radboud University Nijmegen Medical Centre, Medical Centre, Veldhoven, Nijmegen, The Netherlands, 2 Maxima ´ The Netherlands
I. Pascual-Castroviejo1 *, S.-I. Pascual-Pascual1 , R. VelazquezFragua1 , J. Viano ˜ 2 , J.M. Garcia-Segura2 , M.P. Botella3 . 1 University Hospital La Paz, Madrid, Spain, 2 Nuestra Senora ˜ del Rosario Clinic, Madrid, Spain, 3 Hospital Txagorritxu, Vitoria, Spain
Introduction: Ataxia telangiectasie (AT) is an autosomal recessive multisystem disorder characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, increased serum a-fetoprotein, variable immunodeficiency, chromosomal instability, and radiation hypersensitivity. The responsible ATM gene is involved in cell cycle control and DNA repair. With regard to the neuromuscular abnormalities, both axonal polyneuropathy and anterior horn cell disease have been described. To gain more insight in nature and evolution of neuromuscular system involvement in AT we evaluated the clinical, electrophysiological and ultrasonographic findings in 13 patients. Methods: Thirteen classical AT patients, varying in age from 1 to 25 years, were studied clinically, electrophysiologically as well as by muscle ultrasound to chart the development and spectrum of neuromuscular abnormalities in AT. Results: The most prominent finding was a progressive axonal sensorimotor polyneuropathy, electrophysiologically and in ultrasound studies manifest from the age of 8 years and clinically two years later. Additionally, stable slightly decreased sensory nerve conduction velocities could be found as early as the first year of life. With routine electrophysiological techniques the severe polyneuropathy
From a series of 530 patients with neurofibromatosis type 1 (NF1). we performed a retrospective assessment of the long-term neurologic, visual, neuroimaging and evolution of a large series of 80 patients, 58 (72.5%) females and 22 (27.5%) males, with optic pathway glioma (OPG) (incidence 15%). All patients were diagnosed during childhood (below age 16 years) (range 13 months to 15 years and average 4.6 years). Lesion distribution among optic nerves, chiasm, tracts and radiations demonstrated that only 25% of the tumors involved only one optic nerve and 11.5% were located only in the chiasm, while 40% involved one or both optic nerves and chiasm, 12.5% affected both optic nerves, chiasm and tracts, and 11% involved chiasm tracts and radiations. Tumor involvement of chiasm, tracts and radiations showed MRI of marked tumoral widespread and spectroscopic MR (SMR) signs of malignancy in some patients, although these findings did not correspond with histologic and evolutive malignant astrocytoma. Two of these patients showed pilocytic astrocytoma in the histological study. Late diagnosis (after 7 years of age) of OPG was made in three patients and late progression in other three who needed surgical resection, radiotherapy or chemotherapy.
Abstracts: Poster Presentations, the Seventh European Paediatric Neurology Society (EPNS) Congress
pharmacoresistant generalized seizures of various types (tonic, clonic, tonic-clonic, atonic, myoclonic). Unfavourable seizure control was associated with developmental delay. EEGs showed bilateral spike and slow-wave abnormalities. Cerebellar symptoms, paraparesis, difficulties in walk and speech are his main deficits. No abnormalities on brain MRI scans were seen. Conclusion: Our case series confirm the heterogenecity in the clinical and neurophysiological features within the spectrum of hemimegalencephaly and KTWS. NOP06 Ataxia-Telangiectasia: two Bulgarian siblings with the 3576G>A founder mutation on ATM gene P. Dimova1 *, V. Bojinova1 , R. Varon-Mateeva2 , K. Sperling2 . 1 Clinic of Child Neurology, St. Naum University Hospital of Neurology, Sofia, Bulgaria, 2 Institute of Human Genetics, Charita´ Campus Virchow Clinic, Berlin, Germany We present two brothers with delayed diagnosis of ataxia-telangiectasia. Ataxia manifested at the age of 2 and 4 years, respectively. Conjunctival telangiectasia and cerebellar atrophy on brain computed tomography was obvious in both cases at the age of 6 years, while oculomotor and swallowing disturbances, and choreoatetotic movements developed one to two years later. Up to the manifestation of telangiectasia and due to the absence of alpha-fetoprotein elevation and immunoglobulin deficit other cerebellar disorders of childhood were suspected. At the age of purposeful genetic investigation signs of sensorimotor neuropathy and persistent hypoalbuminemia were also present. DNA examination of the siblings revealed a homozygosity for the point mutation 3576G>A on exon 26 of the ATM gene. This mutation leads to exon drop out and aberrant splicing. It has been found more frequently in south and south east Europe, therefore to have a founder effect. Described for the first time in Bulgarian patients, this mutation confirmed the diagnosis in our cases.
precludes conclusions about the presence of anterior horn cell loss in older patients, but we found no post mortem evidence of such loss in a 22 year-old female patient. NOP08 Aqueductal stenosis in the neurofibromatosis type 1 (NF1): presentation of 19 infantile patients I. Pascual-Castroviejo1 *, S.-I. Pascual-Pascual1 , R. VelazquezFragua1 , J. Viano ˜ 2 , F. Carceller3 . 1 Pediatric Neurology Service. University Hospital La Paz, Madrid, Spain, 2 Imagen Unit. Nuestra Sra del Rosario Clinic, Madrid, Spain, 3 Neurosurgery Service. University Hospital La Paz, Madrid, Spain Objective: To present a series of infantile patients with aqueductal stenosis associated with neurofibromatosis type 1 (NF1). Patients and methods: Nineteen patients with ages below 16 years, 11 girls and 8 boys, with NF1 presented hydrocephalus due to aqueductal stenosis. All patients, except one who died before the imagen study was performed and was diagnosed by autopsy, were studied by pneumoencephalography (since 1965 to 1974), computerized tomography (CT) (since 1975 to 1984), magnetic resonance (MR) or MR and CT (since 1985 to 2004) (two children had been studied by pneumoencephalography some years before) most times to discard optic pathway tumor and, in few patients, because of intracranial hypertension. Results: All patients showed threeventricular hydrocephalus with aqueductal stenosis. Eleven patients showed optic pathway tumor. One patient had a benign aqueductal tumor that impaired the normal flow of CSF. Neurological features of hydrocephalus occurred very rapidly in some patients and after several years of evolution in others. Conclusions: Aqueductal stenosis and hydrocephalus were identified at a short age because many patients were studied suspecting optic pathway tumor. Eleven patients (about 60%) associated optic pathway tumor and aqueductal stenosis.
NOP07 Neuromuscular abnormalities in ataxia telangiectasia; a clinical, electrophysiological and muscle ultrasound study
NOP09 Neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG). A series of 80 patients
M.M. Verhagen1 , N. van Alfen1 , M.A. Willemsen1 *, S. Pillen1 , J.-B.L. Yntema1 , J.A. Hiel2 , H. ter Laak1 , M. van Deuren1 , C.M. Weemaes1 . 1 Radboud University Nijmegen Medical Centre, Medical Centre, Veldhoven, Nijmegen, The Netherlands, 2 Maxima ´ The Netherlands
I. Pascual-Castroviejo1 *, S.-I. Pascual-Pascual1 , R. VelazquezFragua1 , J. Viano ˜ 2 , J.M. Garcia-Segura2 , M.P. Botella3 . 1 University Hospital La Paz, Madrid, Spain, 2 Nuestra Senora ˜ del Rosario Clinic, Madrid, Spain, 3 Hospital Txagorritxu, Vitoria, Spain
Introduction: Ataxia telangiectasie (AT) is an autosomal recessive multisystem disorder characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, increased serum a-fetoprotein, variable immunodeficiency, chromosomal instability, and radiation hypersensitivity. The responsible ATM gene is involved in cell cycle control and DNA repair. With regard to the neuromuscular abnormalities, both axonal polyneuropathy and anterior horn cell disease have been described. To gain more insight in nature and evolution of neuromuscular system involvement in AT we evaluated the clinical, electrophysiological and ultrasonographic findings in 13 patients. Methods: Thirteen classical AT patients, varying in age from 1 to 25 years, were studied clinically, electrophysiologically as well as by muscle ultrasound to chart the development and spectrum of neuromuscular abnormalities in AT. Results: The most prominent finding was a progressive axonal sensorimotor polyneuropathy, electrophysiologically and in ultrasound studies manifest from the age of 8 years and clinically two years later. Additionally, stable slightly decreased sensory nerve conduction velocities could be found as early as the first year of life. With routine electrophysiological techniques the severe polyneuropathy
From a series of 530 patients with neurofibromatosis type 1 (NF1). we performed a retrospective assessment of the long-term neurologic, visual, neuroimaging and evolution of a large series of 80 patients, 58 (72.5%) females and 22 (27.5%) males, with optic pathway glioma (OPG) (incidence 15%). All patients were diagnosed during childhood (below age 16 years) (range 13 months to 15 years and average 4.6 years). Lesion distribution among optic nerves, chiasm, tracts and radiations demonstrated that only 25% of the tumors involved only one optic nerve and 11.5% were located only in the chiasm, while 40% involved one or both optic nerves and chiasm, 12.5% affected both optic nerves, chiasm and tracts, and 11% involved chiasm tracts and radiations. Tumor involvement of chiasm, tracts and radiations showed MRI of marked tumoral widespread and spectroscopic MR (SMR) signs of malignancy in some patients, although these findings did not correspond with histologic and evolutive malignant astrocytoma. Two of these patients showed pilocytic astrocytoma in the histological study. Late diagnosis (after 7 years of age) of OPG was made in three patients and late progression in other three who needed surgical resection, radiotherapy or chemotherapy.