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P249 – 1533 A giant congenital melanocytic nevus associated with neurocutaneous melanosis
S122
E U R O P E A N JO U R N A L O F PAEDIATRIC N E U R O L O G Y
17s (2013) S1 – S149
P249 - 1533
P251 - 1689
A giant congenital melanocytic nevus associated with neurocutaneous melanosis
MASA syndrome – report of a two twin brother case
Kim SJ, Han JY, Son B-C, Eom TH. Department of Pediatrics, St. Vincent’s Hospital, College of Medicine, The Catholic University of of Korea, Suwon, South Korea – [email protected] Neuromelanosis (cerebral melanosis), which relates to a congenital error in the morphogenesis of the embryonal ectoderm, describes melanocytic proliferation within the leptomeninges and brain parenchyma. Neurocutaneous melanosis (NCM) is neuromelanosis associated with congenital melanocytic nevi (CMN). It has been reported that many patients with symptomatic NCM die, with more than half of fatalities occurring within initial 3 years of diagnosis. However, asymptomatic NCM is known to have a favorable prognosis. It is uncertain that who will became symptomatic NCM among the patients with asymptomatic NCM. However, a report which studied the magnetic resonance imaging (MRI) finding of asymptomatic NCM patients showed that parenchymal NCM involving characteristic T1 shortening in medial temporal lobe, pons, medulla, and cerebellum had a stable and favorable prognosis. We report a case of a 10 yearold male patient with giant congenital melanocytic nevi (GCMN) and parenchymal NCM diagnosed in his infancy (3 months of age). His neurological condition deteriorated 10 years later with consequent development of leptomeningeal and spinal neuromelanosis. The MRI showed regression and stabilization of T1 hyperintensities (parenchymal NCM) in temporal lobe, cerebellum, and pons. On the contrary, it seemed that diffuse leptomeningeal involvement and enhancement ultimately caused hydrocephalus, seizures, and neurologic deterioration. As shown in our case, parenchymal NCM may not have a clinical significance even after 10 years after diagnosis and the leptomeningeal involvement seems to be a major determinant of the prognosis in patients with NCM.
Kovac Sizgoric M, Sabol Z, Grmoja T, Bela Klancir S, Gjergja Z, Kipke Sabol Lj, Sabol F. Sabol Clinic for Sick Children, Zagreb, Croatia – [email protected] Introduction: MASA syndrome, also called CRASH syndrome and Gareis-Mason syndrome, is a rare X-linked recessive neurological disorder.The acronym “MASA” describes four major symptoms - mental retardation, aphasia, shuffling gait, and adducted thumbs. A more suitable name for this syndrome is “L1 syndrome”. The disorder has been associated with mutations in the L1CAM gene. This syndrome has severe symptoms in males, while females are carriers because only one X-chromosome is affected. The aim of this report is to show similarities and differences between clinical manifestations in twins with the L1CAM gene mutation. Our patients: Born prematurely at 35 weeks gestation. Pregnancy was complicated with early bleeding and gestational diabetes. Immediately after birth hypertonus of the lower extremities in both twins was observed. Sixteen-year clinical follow-up showed spastic paraparetic form with shuffling gait, clumsiness, delayed speech development, with lower intellectual functioning at the level of light to moderate mental retardation, primary nocturnal enuresis, behavioral and sleep disorder (more pronounced in the second twin). Brain MRI in both twins showed complete agenesis of the corpus callosum, complete lack of the anterior commissure, and internal hydrocephalus. EEGs showed nonspecific slower dysrhythmic changes. Kidney ultrasounds showed mild dilatation in the channel system of both kidneys in both twins. Ophthalmologic examinations was normal. Molecular genetic testing (Karl-Franzens-Universität Graz) identified homozygous intron 26 L1CAM gene mutation IVS26-12G→A in both twins. The mother is a carrier of the same heterozygous mutations. Conclusion: Our patients, the twins show similar clinical changes typical of MASA syndrome. After identifying the specific genetic mutations this family has become informative for prenatal diagnosis.
P250 - 1974 Application of array-based comparative genomic hybridization to pediatric neurologic diseases Byeon JH, Shin E, Kim G-H, Kim MK, Eun S-H, Eun B-L. Department of Pediatrics, University College of Medicine, Neodine Medical Institute, Korea – [email protected] Purpose: Array comparative genomic hybridization (array-CGH) is a technique used to analyze the quantitative increase or decrease of chromosomes by competitive DNA hybridization of patients and controls. This study aimed to evaluate the benefits and yield of array-CGH in comparison with palliative karyotyping in pediatric neurology patients. Material and method: We included 87 patients from pediatric neurology clinic with least one of the following features: developmental delay, mental retardation, dysmorphic face, or epilepsy. Extracted DNA from patients and controls were hybridized on the Roche NimbleGen 135K oligonucleotide array and compared with G- band karyotyping. The results were analyzed with findings reported in recent publications and internet databases. Results: Chromosome imbalances, including 9 cases also detected by G-band karyotyping, were found in 28 patients (32.2%), and at least 20 of them seemed to be causally related to the abnormal phenotypes. Regarding each clinical symptom, 26.2% of 42 developmental delay patients, 44.4% of 18 mental retardation patients, 42.9% of 28 dysmorphic face patients, 34.6% of 26 epilepsy patients showed abnormal array results. Conclusion: Although there were a relatively small number of tests in patients with pediatric neurologic disease, this study demonstrated that array-CGH is a very useful tool for clinical diagnosis of unknown genome abnormalities performed in pediatric neurology clinics.
P252 - 2076 Unusual neurological profile in Tunisian children with Williams syndrome Ben Othmen H, Kammoun F, Belguith N, Elouz E, Hsairi I, Kamoun H, Triki C. Research Unit “Neuropédiatrie” 01UR08-05, University of Medicine, Sfax, Tunisia – [email protected] Objectives: Williams syndrome (WS) is a neuro-developmental genetic disorder caused by the hemizygous deletion in chromosome 7q11.23. It is characterized by facial dysmorphism, physical abnormalities and a specific cognitive and behavioral profile. In this report, we look for neurological characteristics. Material and methods: We have reviewed retrospectively 4 girls with WS aged between 4 and 12 years. In all this cases, the diagnosis was based on facial dimorphism, behavior features and the deletion was confirmed by FISH study. We focus on neurological signs and brain investigations (EEG, brain imagery by Computed Tomography (CT) and MRI). Results: Initial consultations for our cases were psychomotor delay in three cases and other neurological abnormalities as hand mirror syncinesia in one case. All patients have abnormal intelligence quotient ranged from mild (n=3) to moderate (n=1). Hyperactive behavior was observed in all cases. CT show bilateral calcifications in the globus pallidus in one case and electroencephalographic abnormalities revealed a rapid diffuse rhythm in one case. Conclusions: Some neurological phenotype associated with mental deficiency can be suggestive of etiology like washing hand stereotypies in Rett and specific EEG patterns in Angelman syndrome. Unlike, previous studies have documented the absence of major neurologic signs in WS and some unusual neurologic profile can dominate the
E U R O P E A N JO U R N A L O F PAEDIATRIC N E U R O L O G Y
17s (2013) S1 – S149
P249 - 1533
P251 - 1689
A giant congenital melanocytic nevus associated with neurocutaneous melanosis
MASA syndrome – report of a two twin brother case
Kim SJ, Han JY, Son B-C, Eom TH. Department of Pediatrics, St. Vincent’s Hospital, College of Medicine, The Catholic University of of Korea, Suwon, South Korea – [email protected] Neuromelanosis (cerebral melanosis), which relates to a congenital error in the morphogenesis of the embryonal ectoderm, describes melanocytic proliferation within the leptomeninges and brain parenchyma. Neurocutaneous melanosis (NCM) is neuromelanosis associated with congenital melanocytic nevi (CMN). It has been reported that many patients with symptomatic NCM die, with more than half of fatalities occurring within initial 3 years of diagnosis. However, asymptomatic NCM is known to have a favorable prognosis. It is uncertain that who will became symptomatic NCM among the patients with asymptomatic NCM. However, a report which studied the magnetic resonance imaging (MRI) finding of asymptomatic NCM patients showed that parenchymal NCM involving characteristic T1 shortening in medial temporal lobe, pons, medulla, and cerebellum had a stable and favorable prognosis. We report a case of a 10 yearold male patient with giant congenital melanocytic nevi (GCMN) and parenchymal NCM diagnosed in his infancy (3 months of age). His neurological condition deteriorated 10 years later with consequent development of leptomeningeal and spinal neuromelanosis. The MRI showed regression and stabilization of T1 hyperintensities (parenchymal NCM) in temporal lobe, cerebellum, and pons. On the contrary, it seemed that diffuse leptomeningeal involvement and enhancement ultimately caused hydrocephalus, seizures, and neurologic deterioration. As shown in our case, parenchymal NCM may not have a clinical significance even after 10 years after diagnosis and the leptomeningeal involvement seems to be a major determinant of the prognosis in patients with NCM.
Kovac Sizgoric M, Sabol Z, Grmoja T, Bela Klancir S, Gjergja Z, Kipke Sabol Lj, Sabol F. Sabol Clinic for Sick Children, Zagreb, Croatia – [email protected] Introduction: MASA syndrome, also called CRASH syndrome and Gareis-Mason syndrome, is a rare X-linked recessive neurological disorder.The acronym “MASA” describes four major symptoms - mental retardation, aphasia, shuffling gait, and adducted thumbs. A more suitable name for this syndrome is “L1 syndrome”. The disorder has been associated with mutations in the L1CAM gene. This syndrome has severe symptoms in males, while females are carriers because only one X-chromosome is affected. The aim of this report is to show similarities and differences between clinical manifestations in twins with the L1CAM gene mutation. Our patients: Born prematurely at 35 weeks gestation. Pregnancy was complicated with early bleeding and gestational diabetes. Immediately after birth hypertonus of the lower extremities in both twins was observed. Sixteen-year clinical follow-up showed spastic paraparetic form with shuffling gait, clumsiness, delayed speech development, with lower intellectual functioning at the level of light to moderate mental retardation, primary nocturnal enuresis, behavioral and sleep disorder (more pronounced in the second twin). Brain MRI in both twins showed complete agenesis of the corpus callosum, complete lack of the anterior commissure, and internal hydrocephalus. EEGs showed nonspecific slower dysrhythmic changes. Kidney ultrasounds showed mild dilatation in the channel system of both kidneys in both twins. Ophthalmologic examinations was normal. Molecular genetic testing (Karl-Franzens-Universität Graz) identified homozygous intron 26 L1CAM gene mutation IVS26-12G→A in both twins. The mother is a carrier of the same heterozygous mutations. Conclusion: Our patients, the twins show similar clinical changes typical of MASA syndrome. After identifying the specific genetic mutations this family has become informative for prenatal diagnosis.
P250 - 1974 Application of array-based comparative genomic hybridization to pediatric neurologic diseases Byeon JH, Shin E, Kim G-H, Kim MK, Eun S-H, Eun B-L. Department of Pediatrics, University College of Medicine, Neodine Medical Institute, Korea – [email protected] Purpose: Array comparative genomic hybridization (array-CGH) is a technique used to analyze the quantitative increase or decrease of chromosomes by competitive DNA hybridization of patients and controls. This study aimed to evaluate the benefits and yield of array-CGH in comparison with palliative karyotyping in pediatric neurology patients. Material and method: We included 87 patients from pediatric neurology clinic with least one of the following features: developmental delay, mental retardation, dysmorphic face, or epilepsy. Extracted DNA from patients and controls were hybridized on the Roche NimbleGen 135K oligonucleotide array and compared with G- band karyotyping. The results were analyzed with findings reported in recent publications and internet databases. Results: Chromosome imbalances, including 9 cases also detected by G-band karyotyping, were found in 28 patients (32.2%), and at least 20 of them seemed to be causally related to the abnormal phenotypes. Regarding each clinical symptom, 26.2% of 42 developmental delay patients, 44.4% of 18 mental retardation patients, 42.9% of 28 dysmorphic face patients, 34.6% of 26 epilepsy patients showed abnormal array results. Conclusion: Although there were a relatively small number of tests in patients with pediatric neurologic disease, this study demonstrated that array-CGH is a very useful tool for clinical diagnosis of unknown genome abnormalities performed in pediatric neurology clinics.
P252 - 2076 Unusual neurological profile in Tunisian children with Williams syndrome Ben Othmen H, Kammoun F, Belguith N, Elouz E, Hsairi I, Kamoun H, Triki C. Research Unit “Neuropédiatrie” 01UR08-05, University of Medicine, Sfax, Tunisia – [email protected] Objectives: Williams syndrome (WS) is a neuro-developmental genetic disorder caused by the hemizygous deletion in chromosome 7q11.23. It is characterized by facial dysmorphism, physical abnormalities and a specific cognitive and behavioral profile. In this report, we look for neurological characteristics. Material and methods: We have reviewed retrospectively 4 girls with WS aged between 4 and 12 years. In all this cases, the diagnosis was based on facial dimorphism, behavior features and the deletion was confirmed by FISH study. We focus on neurological signs and brain investigations (EEG, brain imagery by Computed Tomography (CT) and MRI). Results: Initial consultations for our cases were psychomotor delay in three cases and other neurological abnormalities as hand mirror syncinesia in one case. All patients have abnormal intelligence quotient ranged from mild (n=3) to moderate (n=1). Hyperactive behavior was observed in all cases. CT show bilateral calcifications in the globus pallidus in one case and electroencephalographic abnormalities revealed a rapid diffuse rhythm in one case. Conclusions: Some neurological phenotype associated with mental deficiency can be suggestive of etiology like washing hand stereotypies in Rett and specific EEG patterns in Angelman syndrome. Unlike, previous studies have documented the absence of major neurologic signs in WS and some unusual neurologic profile can dominate the