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Female Duchenne
e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 2 1 ( 2 0 1 7 ) e 2 2 2 ee 2 3 9
months old patient was the younger sister of the first case. She had similar clinical features like her sister. Sequencing of two siblings revealed a novel homozygous frameshift mutation p.N55Mfs*16 (c.163_163delA) within the LAMA2 gene. Discussion: This mutation is leading to a premature stop codon and no reported in the literatu¨re. This study emphasize that in individual with congenital hypotonia, muscle weakness, elevated serum creatine kinase level and white matter abnormalities MDC1A should be kept in mind.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1242 P3-133 A large nationwide multicenter observational study: Characterizing myotonic dystrophy type 1 spectrum in pediatric patients E. Lagrue, C. Dogan, M. De Antonio, D. Hamroun, B. Eymard, G. Bassez. CHRU de Tours, Universite Franc¸ois Rabelais de Tours, INSERM U930, Tours, France Objective: Myotonic Dystrophy type 1 (DM1) is known to exhibit marked phenotypic disparities due to highly variable age of onset and heterogeneous multisystemic involvement. Despite recent clinical progress concerning DM1 adult forms characterization, pediatric descriptions though remain scarce, relying on limited series of patients thus often not encompassing the whole clinical spectrum. We therefore aimed to phenotypically characterize a wide MD1 pediatric cohort to provide a solid frame of data for future evidence-based health management in this population. Methods: The French DM-Scope registry was used to set up the largest multicentric pediatric DM1 observational study so far. Among the total 2202 DM patients included in the registry, the pedDM-Scope study enrolled all genetically confirmed DM1 patients less than 18 years old, whose data were collected by 24 neuropediatric centers. Comprehensive crosssectional analysis of most relevant qualitative and quantitative variables was performed. Results: 304 patients (49% females) were analyzed. They had congenital (38%), infantile (48%) and juvenile (14%) DM1 forms with a high paternal transmission rate (9%, 39.2%, 65.6% respectively). An inverse correlation between the age at onset and the CTG repeat length was found. Widespread highly prevalent neurodevelopmental alterations, including slowness (85%) and facial dysmorphism (69.5%), were detected in the three forms. 5.5% exhibited autism spectrum disorders. Over-all musculo-skeletal impairment was mild, walking inability being absent in infantile and juvenile forms and accounting for less than 4% of congenital form patients. Despite low prevalence, heart and respiratory impairment could be life-threatening and 4.3% of patients required a pacemaker. Other manifestations, such as gastrointestinal symptoms (27%) and cataracts (9%) were more frequent than expected. Conclusion: Detailed genotype and phenotype data provided by the pedDM-scope study in DM1 pediatric subgroups will facilitate both tailored health care management (including transition into adulthood) and health policy future planning in this lifelong disease.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1243
e229
P3-134 Female Duchenne . Department of Pediatric Neurology, J. Sekelj Fure s, V. Ðuranovic Children's Hospital, Zagreb, Croatia Objective: Duchenne muscular dystrophy (DMD) is a X-linked recessive disease caused by mutations in dystrophin gene and is characterized by progressive muscle degeneration and weakness resulting in poor disease outcome. The disease primarily affects boys. Females are usually only asymptomatic carriers of mutations. Manifesting carriers are those with muscle weakness and/or dilated cardiomyopathy and asymptomatic are considered those with elevated levels of creatine kinase, and/or minor myopathic signs such as myalgia or muscle cramps. Methods: Our patient is a girl in which disease manifested at the age of 13, with muscle weakness and exercise tolerance. During the last two years her problems became more pronounced and we started diagnostic workup under the suspicion of neuromuscular disease. Besides the clear signs of muscle weakness, particularly expressed in the proximal muscles of the lower extremities with positive Gowers sign, she had hypertrophy of the calves. Repeated cardiac examination was normal. Results: We performed initial laboratory testing and observed elevated creatine kinase (CK) 10 times more than the reference value. EMG analysis was of regular neurographic parameters but needle EMG showed pronounced spontaneous outbreak with myopathic pattern. We performed muscle biopsy and histological examination revealed the destructive myopathic process and immunohistochemistry complete absence of dystrophin expression. MLPA revealed a heterozygous deletion of exon 3 and 4 of dystrophin gene. Conclusion: Our female patient most likely has de novo mutation of dystrophin gene that led to expression of symptoms at an earlier age than the average mentioned in literature, symptoms are progressive, and the girl is already difficult to stay ambulatory and we think that she has atypical form of dystrophinopathy with complete absence of dystrophin in muscle biopsy. Nowadays, for our patient besides genetic counseling it is very important to consider medicamentous treatment.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1244 P3-135 Phenotypic variability of myopathies associated with LAMA2 gene mutations Filipe Palavra, Carmen Costa, Vera Ribeiro, Henriqueta Arau´jo, Isabel Fineza. Centre for Child Development, Neuropediatrics Unit, Pediatric Hospital, Coimbra Hospital and University Centre, Faculty of Medicine, University of Coimbra, Coimbra, Portugal Introduction: LAMA2 gene encodes the a2 chain of merosin and its mutations usually result in severe congenital muscular dystrophy (CMD). More than 140 mutations have been described, which frequently lead to total loss of merosin function. Less severe cases with a limb-girdle-type muscular dystrophy have also been described, expanding the phenotype of these clinical conditions. Objective: To describe the characteristics of patients with LAMA2related myopathies which have been followed in our Neuromuscular Disorders clinic. Methods: This is an observational and descriptive study, based on the consultation of the hospital files of patients with LAMA2 mutations and who have attended (or attended) the Neuromuscular Disorders clinic, since 1980. Demographic, clinical, imagiological, histopathological and genetic variables were collected.
months old patient was the younger sister of the first case. She had similar clinical features like her sister. Sequencing of two siblings revealed a novel homozygous frameshift mutation p.N55Mfs*16 (c.163_163delA) within the LAMA2 gene. Discussion: This mutation is leading to a premature stop codon and no reported in the literatu¨re. This study emphasize that in individual with congenital hypotonia, muscle weakness, elevated serum creatine kinase level and white matter abnormalities MDC1A should be kept in mind.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1242 P3-133 A large nationwide multicenter observational study: Characterizing myotonic dystrophy type 1 spectrum in pediatric patients E. Lagrue, C. Dogan, M. De Antonio, D. Hamroun, B. Eymard, G. Bassez. CHRU de Tours, Universite Franc¸ois Rabelais de Tours, INSERM U930, Tours, France Objective: Myotonic Dystrophy type 1 (DM1) is known to exhibit marked phenotypic disparities due to highly variable age of onset and heterogeneous multisystemic involvement. Despite recent clinical progress concerning DM1 adult forms characterization, pediatric descriptions though remain scarce, relying on limited series of patients thus often not encompassing the whole clinical spectrum. We therefore aimed to phenotypically characterize a wide MD1 pediatric cohort to provide a solid frame of data for future evidence-based health management in this population. Methods: The French DM-Scope registry was used to set up the largest multicentric pediatric DM1 observational study so far. Among the total 2202 DM patients included in the registry, the pedDM-Scope study enrolled all genetically confirmed DM1 patients less than 18 years old, whose data were collected by 24 neuropediatric centers. Comprehensive crosssectional analysis of most relevant qualitative and quantitative variables was performed. Results: 304 patients (49% females) were analyzed. They had congenital (38%), infantile (48%) and juvenile (14%) DM1 forms with a high paternal transmission rate (9%, 39.2%, 65.6% respectively). An inverse correlation between the age at onset and the CTG repeat length was found. Widespread highly prevalent neurodevelopmental alterations, including slowness (85%) and facial dysmorphism (69.5%), were detected in the three forms. 5.5% exhibited autism spectrum disorders. Over-all musculo-skeletal impairment was mild, walking inability being absent in infantile and juvenile forms and accounting for less than 4% of congenital form patients. Despite low prevalence, heart and respiratory impairment could be life-threatening and 4.3% of patients required a pacemaker. Other manifestations, such as gastrointestinal symptoms (27%) and cataracts (9%) were more frequent than expected. Conclusion: Detailed genotype and phenotype data provided by the pedDM-scope study in DM1 pediatric subgroups will facilitate both tailored health care management (including transition into adulthood) and health policy future planning in this lifelong disease.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1243
e229
P3-134 Female Duchenne . Department of Pediatric Neurology, J. Sekelj Fure s, V. Ðuranovic Children's Hospital, Zagreb, Croatia Objective: Duchenne muscular dystrophy (DMD) is a X-linked recessive disease caused by mutations in dystrophin gene and is characterized by progressive muscle degeneration and weakness resulting in poor disease outcome. The disease primarily affects boys. Females are usually only asymptomatic carriers of mutations. Manifesting carriers are those with muscle weakness and/or dilated cardiomyopathy and asymptomatic are considered those with elevated levels of creatine kinase, and/or minor myopathic signs such as myalgia or muscle cramps. Methods: Our patient is a girl in which disease manifested at the age of 13, with muscle weakness and exercise tolerance. During the last two years her problems became more pronounced and we started diagnostic workup under the suspicion of neuromuscular disease. Besides the clear signs of muscle weakness, particularly expressed in the proximal muscles of the lower extremities with positive Gowers sign, she had hypertrophy of the calves. Repeated cardiac examination was normal. Results: We performed initial laboratory testing and observed elevated creatine kinase (CK) 10 times more than the reference value. EMG analysis was of regular neurographic parameters but needle EMG showed pronounced spontaneous outbreak with myopathic pattern. We performed muscle biopsy and histological examination revealed the destructive myopathic process and immunohistochemistry complete absence of dystrophin expression. MLPA revealed a heterozygous deletion of exon 3 and 4 of dystrophin gene. Conclusion: Our female patient most likely has de novo mutation of dystrophin gene that led to expression of symptoms at an earlier age than the average mentioned in literature, symptoms are progressive, and the girl is already difficult to stay ambulatory and we think that she has atypical form of dystrophinopathy with complete absence of dystrophin in muscle biopsy. Nowadays, for our patient besides genetic counseling it is very important to consider medicamentous treatment.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1244 P3-135 Phenotypic variability of myopathies associated with LAMA2 gene mutations Filipe Palavra, Carmen Costa, Vera Ribeiro, Henriqueta Arau´jo, Isabel Fineza. Centre for Child Development, Neuropediatrics Unit, Pediatric Hospital, Coimbra Hospital and University Centre, Faculty of Medicine, University of Coimbra, Coimbra, Portugal Introduction: LAMA2 gene encodes the a2 chain of merosin and its mutations usually result in severe congenital muscular dystrophy (CMD). More than 140 mutations have been described, which frequently lead to total loss of merosin function. Less severe cases with a limb-girdle-type muscular dystrophy have also been described, expanding the phenotype of these clinical conditions. Objective: To describe the characteristics of patients with LAMA2related myopathies which have been followed in our Neuromuscular Disorders clinic. Methods: This is an observational and descriptive study, based on the consultation of the hospital files of patients with LAMA2 mutations and who have attended (or attended) the Neuromuscular Disorders clinic, since 1980. Demographic, clinical, imagiological, histopathological and genetic variables were collected.