Clinical Neuroscience

Neurogenetic Diseases - Diagnostic and Therapy Issues Report of the 1st Scientific Meeting on Neurogenetics

NOVEMBER 20, 1997

Clinical Neuroscience - 1997;50(11-12)

Basic molecular genetics concepts. Basic concepts of non-traditional inheritance. The importance of Southern hybridisation and PCR techniques in the diagnosis of genetic diseases. The study of a gene in a specific disease. How to investigate inherited neurodegenerative diseases in children. Factors complicating the detection of a new transthyretin mutation (TTRAsp18Gly). The role of genetic testing in neurology. Structure of the genetic laboratory. Neurogenetic tests that can be performed in Hungary. Newer possibilities for genetic diagnosis of spinal muscular atrophy. Experience of prenatal testing. Neurological pathologies caused by trinucleotide repeat expansion. Molecular genetic diagnosis of Huntington's disease and its problems. Introduction of molecular genetic detection of fragile X disease in our country. Genetic aspects of von Hippel-Lindau disease. Advances in molecular genetics in inherited neuromuscular diseases. First domestic experience in molecular genetic diagnosis of Charcot-Marie-Tooth type 1 peripheral neuropathy. Heterozygote testing problems in Duchenne-Becker-type myopathies. Analysis of IQ and genotype in Duchenne and Becker muscular dystrophy. Primary mitochondrial myopathies. Non-primary mitochondriopathies based on aberrations of mtDNA. Our experience in processing Hungarian cases of Leber's hereditary optic neuropathy. Detection of mitochondrial deletions by PCR. Recent data on the genetic basis of some epilepsy syndromes. New insights into the genetics of epilepsy. Lysosomal patients in the ten-year patient database of our department. Biochemical diagnosis of inherited neuro-metabolic diseases. Neurogenetics in Germany. Prospect for gene therapy for the nervuous system and muscle. Preclinical research on gene therapy for Duchenne muscular dystrophy. Absence of apoe e4 allele in the neurofibrillary tangle subset of senile dementia. Mitochondrial DNA sequence variiaton of complex I genes in Parkinson's disease. Aging in epilepsy - a Hungarian multicentre study. Decrease in antiepileptic effect in pregnant women with epilepsy given a folic acid-containing multivitamin. Molecular genetic study of heredoataxia (SCAl, SCA2, SCA3, FA). Atrophy olivopontocerebellaris (Déjeriné-André-Thomas). Diagnostic problems. Hereditary Motor and Sensory Neuropathies (HMSN) in Southern Burgenland and Vicinity. Apolipoprotein E e4 allele frequency in patients with multiple system atrophy. Expression of nitric oxide synthase (NOS) isoforms in skeletal muscle of patients with mitochondrial. Pedigree analysis of hungarian Rett syndrome girls. Epidemiological studies in a population with Huntington's disease in Western Transdanubia. The role of psychological factors in the counselling and care of individuals at risk for Huntington's disease. Lesch-Nyhan syndrome . Clinical analysis of type II spinal muscular atrophy. Familial scapuloperoneal syndrome and mitochondrial DNA defects. The use of rilutes in familial ALS. Addison's disease and symptoms - adrenoleukodystrophy Case report. On familial hemiplegic migraine. Examination of somatic mutations in cadaveric brain samples. EMG and genetic diagnosis of paramyotonia congenita. CTG-triplet expansion study in a three-generation family with myotonia dystrophy.

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[Antecendents and epilepsy in dyskinetic/dystonic cerebral palsy]

BALOGH Erzsébet, KOZMA Gyuláné, VARGÁNÉ Kiss Anna

[The rate of cerebral palsy (1-3/1000) is not diminishing, but the prevalence of athetosis seems to be decreasing. 234 athetosis cases (born 1972–1992) have been studied in Budapest (n=149) and in London (n=85) for birth weight, icterus, hypoxia and/or neonatal convulsion and epilepsy. The majority of athetosis cases were born with a birth weight above 2500 g. Kernicterus has not been found, but 43.3% (Budapest) and 75.3% (London) of the cases showed clinical signs of hypoxia with or without perinatal convulsion. Hypoxia and icterus were rarely found together. Athetosis with epilepsy occurred in one fourth and one third of the cases, respectively. Long term hypoxia of mature infants has to see the most relevant risk factor for the severe cerebral palsy with (29.5% Budapest, 23.5% London) and without epilepsy.]

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HERCZEGFALVI Ágnes, KARCAGI Veronika, TÍMÁR László

[The three most common types of childhood spinal muscular atrophy (SMA) are type I or Werdnig Hoffmann disease, type II or intermediate form, and type III or Kugelberg-Welander disease. The clinical features of these three types are characteristic, profound limb hypotonia, wasting of muscles and areflexia. All three forms of SMA reveal an autosomal recessive mode of inheritance. The gene responsible for all three types of SMA is located on the long arm of chromosome 5 in the region of 5q11.2-913.3. Starting from 1993 blood samples were collected from 87 Hungarian families with all 3 types of SMA. DNA samples of all family members were analysed with the currently available highly informative microsatellite DNA markers in the locus 5q11.2 q13.3. Moreover, affected persons and their family members have been analysed for deletions of the survival of motor neuron gen (SMN). Prenatal diagnoses were performed in 28 cases at the request of the affected families. The possibility of prenatal diagnosis is a major step forward in helping these families, as the risk of recurrence of this devasting, untreatable disease is 25% in affected families.]

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[Prognosis of newborns of very low birthweight]

BEKE Anna, FEHÉRNÉ Szekszárdi Márta, CSIKY Erzsébet, KUCSERÁNÉ Gráf Rózsa, NÉMETH Tünde, SZABÓ Györgyné

[Development of 357 ventilated newborns born from January 1989 to 30 September 1996, who weighed 1500 gm or less at birth, was investigated in follow-up studies. Of the 357 infants, 9 died after one month of age. The outcome of 348 survivors was followed up by a team after the same protocol. Infants were divided into two groups according to year of birth. In the first four-year group, there were 168 children (from 1989 to 1992), in the second one there were 180 children (from 1993-1996). The two periods are different in the obstetrical and neonatological therapeutic methods. Comparing the results of follow-up studies, the authors investigated the influence of the new therapeutic methods on the neonatal morbidity and prognosis of newborns of very-low birthweigt. Although the survival rate increased from 61% to 78% between the two four-year periods, and the survival rate of newborns of very very low birth weight became two times higher (from 19.8% to 41 %), the neurological morbidity (rate of cerebral palsy), did not changed essentially. Important improvement was found in the ophthalmological outcome. The conclusion is that the quality of life for infants and children born of very-low birthweight has not yet improve significantly in every area of development.]

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[We examined the role of HMPAO SPECT examinations in presurgical evaluation of children with intractable partial epilepsy. SPECT studies (ictal, interictal) were performed on 31 children aged 1-18 years. The focus was restricted in 18 cases and extensive, ie, a whole hemisphere or some lobes, in 4 cases. SPECT indicated pathological changes in the relevant areas in 15 of 18 cases, but in 9 children with temporal epilepsy in all. The focus was extensive in 4 cases, e.g. in 3 children with Rasmussen syndrome. SPECT was pathologic in all of them when MRI did not yet show hemiatrophy of the brain. In 3 cases of partial epilepsy MRI did not demonstrate lesion, the focus was not well-defined by EEG, in contrast to SPECT. Thus it can be stated that SPECT provides valuable information on presurgical evaluation in children with intractable partial epilepsy.]

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[Comparative study of digital subtraction angiography and MR-angiography in ischemic stroke of children]

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[A report is given on 10 children suffering from ischemic stroke. In all children the ischemic lesions were confirmed by CT scans. The patients underwent both Digital Subtraction Angiography (DSA) and MRA. In five cases of stenotic or occlusive changes the MRA correlated well with DSA findings. However 3 cases of moyamoya disease, 1 case of arterial spasm and 1 case of stenotic change were not shown on MRA. MRA can be a valuable alternative method to DSA in occlusion of major intracerebral arteries.]

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