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Assessment of developmental dysgraphia
kemia using vincristine methotrexate and L-asparaginase intravenously or intramuscularly and cytosine arabinoside (Ara-C) intrathecally, there was improvement in clinical features and normalization of VEEG findings and CSF but not serum serology. We propose that Ara-C given intrathetically might have inactivated the measles virus in the central nervous system by inhibiting the defective viral replication through host DNA template. Ara-C may offer a therapeutic advantage in the early stages of SSPE.
95. A S S E S S M E N T O F D E V E L O P M E N T A L DYSGRAPHIA Sasson S. Gubbay and Nicholas H. de Klerk, Perth, Western Australia
Developmental dysgraphia may be defined as impairment of the normal development of writing skills. A significant delay in writing as in any learning function may be arbitrarily defined as when the child performs more than 2 S.D. below the mean for age. We provide a neurologic classification of developmental dysgraphia into aphasic, apraxic, and mechanical types and describe standardized tests of handwriting which could rapidly identify children with these various categories of dysgraphia. The study is based on a population of 259 normal 13- and 14year-old schoolchildren. The most useful tests for discriminating between subgroups include the spelling of words, non-words, objects and actions, and mirror writing. The classification and testing format may assist the clinician in both counselling and remediation of a particular child. They could also be used for correlation with imaging studies or in epidemiologic surveys of neurodevelopmental disorders.
96. I M P O R T A N C E O F M R I IN D I A G N O S I S OF FRIEDREICH ATAXIA Eray Dirik, Feridun Ozdamar, Ozden Anal, and Tugrnl Pirnar, Izmir, Turkey
Friedreich ataxia (FA), a multisystemic degenerative disorder, affects the peripheral nerves, spinal cord, heart, and carbohydrate metabolism [1]. There has been no definitive diagnostic laboratory examination for FA. Diagnosis rests on the presence of the expected clinical manifestations and sometimes on family history [2]. A 12-year-old girl is presented with a 2-year history of slowly progressive ataxia. Physical examination revealed absent deep tendon reflexes and absent vibration and position senses, particularly in the lower extremities. Babinski sign and Romberg tests were positive. There were no pathologic findings on cranial CT or MRI except for a mild atrophic pattern in the pons and medulla oblongata. Spinal MRI was performed and severe shrinkage of the spinal cord was found, especially in the cervical part. This patient in whom the diagnosis of FA was established with both clinical and neuroradiologic findings is discussed especially noting the importance of MRI in the differential diagnosis of this entity. References: [1] Klein EA, Steinborn E. Spinocerebellar degeneration. In: Swaiman KF, ed. Pediatric neurology principles and practice. St. Louis: The C.V. Mosby Company, 1989;839-43. [2] Harding AE. Friedreich's ataxia: A clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features. Brain 1981;104:589-620.
110 PEDIATRIC NEUROLOGY Vol. 11 No. 2
97. PRELIMINARY ANALYSIS OF H E R E D I T A R Y MODEL AND MITOCHONDRION DNA IN RETT SYNDROME Xinhua Bao and Xiru Wu, Beijing, China
Rett syndrome is an infantile neurologic disorder characterized by psychomotor deterioration and autistic behavior with presentation at 6-18 months of life. Its hereditary model is proposed as X-linked-dominant inheritance which is lethal in males. The possibility of nonrandom X chromosome inactivation in patients and their mothers is suggested. The pathologic change in mitochondrion has been reported, but it is not clear whether the lesion is caused by nuclear DNA mutation or by mtDNA mutation. We found that in patients' mothers the spontaneous abortion rate (10.5%) and the stillbirth rate (0%) were not greater than that of the general population. These findings do not support the hypothesis that Rett syndrome is lethal in males in embryo. The incidence of nonrandom X chromosome inactivation in peripheral blood leukocytes increases in patients and their mothers (3/4 and 3/5, respectively) compared with healthy controls (1/5). The results suggest that nonrandom X chromosome inactivation may be functional in the hereditary process. A variant RFLP of the probe pSPT/PGK in one patient's mother was found. It is unknown whether this variant of RFLP relates to Rett syndrome. No large fragment deletion was found in the mtDNA by PCR analysis.
98. TWO DE NOVO MUTATIONS OF MUSCLE MITOC H O N D R I A L DNA IN MITOCHONDRIAL MYOPATHIES Yu Qi, Qingtang Chen, Xiaodong Li, and Xiru Wu, Beijing, China
We report the molecular studies of skeletal muscle from 17 patients with mitochondrial myopathies. Two new types of mutations were identified by using Southern hybridization after restriction digestion with Pvu II, EcoR I, Hind III, and Sac I, and polymerase chain reaction of 2,179 base pairs in size. Double deletions on two separate sites of mitochondrial DNA were found in a patient with Kearns-Sayer syndrome (KSS) while most reports described single site depletions in almost all KSS patients. PCR amplification, restriction endonuclase Pvu II digestion, and direct sequencing demonstrate another point mutation inducing a novel Pvu II site in a patient with chronic, progressive external ophthalmoplegia (CPEO). This is the first reported point mutation affecting ND4 in published CPEO patients, one-half of whom harbor large deletions in their mitochondrial genome. Based on these findings, the possibility of a unique Chinese mutation pattern is discussed, including an alternative ratio between defective mtDNA and wild-type mtDNA among affected individuals and the general population.
99. MULTIPLE SCLEROSIS IN CHILDHOOD Eray Dirik and Alp ~en, Izmir, Turkey
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that is rarely seen in children. Only 5% of all patients with MS experience onset before 16 years of age and there are only 16 patients reported to be younger than 6 years of age [1,2]. One of our patients was a 6-year-old boy who had
95. A S S E S S M E N T O F D E V E L O P M E N T A L DYSGRAPHIA Sasson S. Gubbay and Nicholas H. de Klerk, Perth, Western Australia
Developmental dysgraphia may be defined as impairment of the normal development of writing skills. A significant delay in writing as in any learning function may be arbitrarily defined as when the child performs more than 2 S.D. below the mean for age. We provide a neurologic classification of developmental dysgraphia into aphasic, apraxic, and mechanical types and describe standardized tests of handwriting which could rapidly identify children with these various categories of dysgraphia. The study is based on a population of 259 normal 13- and 14year-old schoolchildren. The most useful tests for discriminating between subgroups include the spelling of words, non-words, objects and actions, and mirror writing. The classification and testing format may assist the clinician in both counselling and remediation of a particular child. They could also be used for correlation with imaging studies or in epidemiologic surveys of neurodevelopmental disorders.
96. I M P O R T A N C E O F M R I IN D I A G N O S I S OF FRIEDREICH ATAXIA Eray Dirik, Feridun Ozdamar, Ozden Anal, and Tugrnl Pirnar, Izmir, Turkey
Friedreich ataxia (FA), a multisystemic degenerative disorder, affects the peripheral nerves, spinal cord, heart, and carbohydrate metabolism [1]. There has been no definitive diagnostic laboratory examination for FA. Diagnosis rests on the presence of the expected clinical manifestations and sometimes on family history [2]. A 12-year-old girl is presented with a 2-year history of slowly progressive ataxia. Physical examination revealed absent deep tendon reflexes and absent vibration and position senses, particularly in the lower extremities. Babinski sign and Romberg tests were positive. There were no pathologic findings on cranial CT or MRI except for a mild atrophic pattern in the pons and medulla oblongata. Spinal MRI was performed and severe shrinkage of the spinal cord was found, especially in the cervical part. This patient in whom the diagnosis of FA was established with both clinical and neuroradiologic findings is discussed especially noting the importance of MRI in the differential diagnosis of this entity. References: [1] Klein EA, Steinborn E. Spinocerebellar degeneration. In: Swaiman KF, ed. Pediatric neurology principles and practice. St. Louis: The C.V. Mosby Company, 1989;839-43. [2] Harding AE. Friedreich's ataxia: A clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features. Brain 1981;104:589-620.
110 PEDIATRIC NEUROLOGY Vol. 11 No. 2
97. PRELIMINARY ANALYSIS OF H E R E D I T A R Y MODEL AND MITOCHONDRION DNA IN RETT SYNDROME Xinhua Bao and Xiru Wu, Beijing, China
Rett syndrome is an infantile neurologic disorder characterized by psychomotor deterioration and autistic behavior with presentation at 6-18 months of life. Its hereditary model is proposed as X-linked-dominant inheritance which is lethal in males. The possibility of nonrandom X chromosome inactivation in patients and their mothers is suggested. The pathologic change in mitochondrion has been reported, but it is not clear whether the lesion is caused by nuclear DNA mutation or by mtDNA mutation. We found that in patients' mothers the spontaneous abortion rate (10.5%) and the stillbirth rate (0%) were not greater than that of the general population. These findings do not support the hypothesis that Rett syndrome is lethal in males in embryo. The incidence of nonrandom X chromosome inactivation in peripheral blood leukocytes increases in patients and their mothers (3/4 and 3/5, respectively) compared with healthy controls (1/5). The results suggest that nonrandom X chromosome inactivation may be functional in the hereditary process. A variant RFLP of the probe pSPT/PGK in one patient's mother was found. It is unknown whether this variant of RFLP relates to Rett syndrome. No large fragment deletion was found in the mtDNA by PCR analysis.
98. TWO DE NOVO MUTATIONS OF MUSCLE MITOC H O N D R I A L DNA IN MITOCHONDRIAL MYOPATHIES Yu Qi, Qingtang Chen, Xiaodong Li, and Xiru Wu, Beijing, China
We report the molecular studies of skeletal muscle from 17 patients with mitochondrial myopathies. Two new types of mutations were identified by using Southern hybridization after restriction digestion with Pvu II, EcoR I, Hind III, and Sac I, and polymerase chain reaction of 2,179 base pairs in size. Double deletions on two separate sites of mitochondrial DNA were found in a patient with Kearns-Sayer syndrome (KSS) while most reports described single site depletions in almost all KSS patients. PCR amplification, restriction endonuclase Pvu II digestion, and direct sequencing demonstrate another point mutation inducing a novel Pvu II site in a patient with chronic, progressive external ophthalmoplegia (CPEO). This is the first reported point mutation affecting ND4 in published CPEO patients, one-half of whom harbor large deletions in their mitochondrial genome. Based on these findings, the possibility of a unique Chinese mutation pattern is discussed, including an alternative ratio between defective mtDNA and wild-type mtDNA among affected individuals and the general population.
99. MULTIPLE SCLEROSIS IN CHILDHOOD Eray Dirik and Alp ~en, Izmir, Turkey
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that is rarely seen in children. Only 5% of all patients with MS experience onset before 16 years of age and there are only 16 patients reported to be younger than 6 years of age [1,2]. One of our patients was a 6-year-old boy who had