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P190 – 2307: Epidemiological study of Japanese Rett syndrome
EUROPEAN JOURNAL O F PAEDIATRIC NEUROLOGY
video: first voluntary movements, weaning from the ventilator, enduring neuropathic pain, ability to sit and stand. Conclusion: Recording the video was an additional incentive for our patient to work hard during rehabilitation to regain all lost abilities. Because of her passion for singing she could be motivated more easily.
Rett Syndrome
19s (2015) S1 – S152
S147
estimated prevalence of RTT patients in Japan was 0.90 per 10,000 girls. It revealed the local clustering of hospitals, which provide the medical service for RTT patients. Interestingly, over 80% of five main symptoms appeared in typical RTT patients until 3 year-old. Conclusion: This is the first nationwide survey of RTT in Japan. It gave a prevalence of concomitant with previous studies in other countries. We have established the clinical and genetic database of Japanese RTT patients. Next, we have to use the database for clinical research to explore biological markers and treatment, with or without international collaborations.
P189 - 2279 Is the regression period in Rett syndrome well defined and easy to recognize? A.M. Bisgaard, M. Stahlhut, J.L. Larsen, B. Syhler, B. Schönewolf-Greulich. Centre for Rett syndrome, Department of Clinical Genetics – Kennedy Centre, Rigshospitalet, Copenhagen, Denmark Objective: In order to increase knowledge of regression as a clue to diagnose Rett syndrome (RTT), we want to investigate if the regression period (RP) is well defined and easy to recognize. Methods: Medical records (including questionnaires and interviews) were reviewed concerning the RP in children with clinical Rett syndrome and a MECP2 mutation referred to the nation-wide Centre for Rett syndrome in Denmark in the years 2012–2014. Results: Ten girls with RTT (8 typical/2 atypical) and a MECP2 mutation aged 1.7–5.3 years (mean 3.3 years; median 2.8 years) were referred to the centre and evaluated within 13–152 days (mean 58.3 days; median 41.5 days). Seven of the girls were post regression at this first evaluation. In the other 3 cases it was difficult to conclude but time showed that 2 girls were still in regression at the first visit. The girls were in RP in the range of about 4–35 months (mean 14.8 mo; median 12 mo). Before the RTT diagnosis 5 of the girls were referred to psychiatric evaluation at a time that turned out to be in the RP. One of these girls and 3 others had a muscular biopsy before (2), under (1) or after (1) an unrecognized RP. One girl had severe symptoms of epilepsy and adverse reactions to medication in RP. In 6 cases the RP along with other symptoms as handstereotypies led to suspicion of RTT. Five of the girls were diagnosed in the RP and the other 5 after the RP. Conclusion: In most of our cases, RP was not well defined or easily recognized. It might be overlooked because of its long and slow progression as well as co-morbidities like hypotonia or epilepsy. We conclude that more information regarding regression in RTT is needed to facilitate early diagnosis, counselling and treatment.
P191 - 2505 Two siblings with a CDKL5 mutation: Genotype and phenotype evaluation E.E.O. Hagebeuk, C.L. Marcelis, M. Alders, A. Kaspers, A.W. de Weerd. Department of Pediatric Neurology, Stichting Epilepsie Instellingen Nederland (SEIN), Zwolle, The Netherlands Objective: This is the second report of a family with a recurrence of a CDKL5 mutation (c. 283-3_290del) in two sisters. Their phenotype is different despite an identical genotype Clinically CDKL5 patients resemble those with Rett syndrome, caused by a MECP2 mutation, who experience a regression, after an initial normal development. However, CDKL5 patients experience a developmental delay from from birth onwards and seizures starts the first three months of life. Methods: Advanced genetic evaluations of the sisters and parents, the electropherogram, clinical and electroencephalographic (EEG) features of both sisters are discussed. Results: In the youngest patient, who was known to us prior to appearance of the clinical symptoms, neurological and EEG evaluations at the age of 6 weeks were normal. Infantile spasms evolved at the age of 10 weeks. Simultaneously, she showed a psychomotor regression and deterioration of the EEG into a severe epileptic pattern. Her older sister, was from the start severely hypotonic, had a developmental delay (without regression) and feeding problems and experiences seizures from the age of 8 weeks. In both seizures are refractory. The phenotype of the youngest sister is worse than that of her older sister, despite an identical genotype. This may be explained by differences in X-chromosomal inactivation and other unknown epigenetic and environmental factors. Unfortunately, X inactivation pattern could not be determined in the youngest sister. Both parents tested negative for the mutation in all tissues, but germline mosaicism is likely. Conclusion: This report of familial recurrence with suspected germline mosaicism in a healthy parent, has important consequences for genetic counselling. Although it is not possible to predict an exact recurrence risk, it is likely to be increased.
P190 - 2307 Epidemiological study of Japanese Rett syndrome M. Itoh, S. Nabatame, H. Tachimori, T. Matsuishi. National Center of Neurology and Psychiatry Objective: It has known that a prevalence of Rett syndrome (RTT) is approximately 1.0 per 10,000 females. However, we have never Japanese data. In 2010, the recent revised criterion for diagnosis of RTT was published. Here, we performed nationwide survey of RTT, according to the new criterion, to clarify the Japanese epidemiology of RTT. Methods: We selected 1,020 hospitals or institutes by stratified sampling from 2,918 ones specialized for pediatrics and pediatric neurology in Japan. We sent the first questionnaire to them to ask the number of RTT patients each institute followed from 2008 to 2009. After responded, we asked clinical details with the second questionnaire. Results: We received 677 responses from 1,020 hospitals (total response rate: 66.4%), and they counted 480 definite RTT patients and 79 atypical patients. The estimated total number of definite RTT patients was 1011 (95% confidential interval, 778–1244), and the
P192 - 2531 Overview of Rett syndrome associated with MECP2 mutation: Analysis of 7 patients I. Erol, S. Yetkinel, T. Savas. Associate Professor, Baskent University Faculty of Medicine, Department of Pediatrics, Neurology Division, Adana Teaching and Medical Research Center, Adana, Turkey Objective: The aim of the present study was to report our experience with Rett syndrome (RTT) associated with MECP2 mutation. Methods: Seven consecutive patients diagnosed with RTT associated with MECP2 mutation in our child neurology clinic were analyzed in terms of clinical findings retrospectively. Diagnosis were compared according to revised diagnostic criteria (2010) for RTT. Results: There were 7 girls, age range, 2.3 to 10.2 years. Age at the time of diagnosis were 2 to 5 years. Although 2 of the child had history of preterm birth. All of the patient had normal psychomotor development in first six months of life. Therefore none of the patient had any exclusion criteria. All of the
video: first voluntary movements, weaning from the ventilator, enduring neuropathic pain, ability to sit and stand. Conclusion: Recording the video was an additional incentive for our patient to work hard during rehabilitation to regain all lost abilities. Because of her passion for singing she could be motivated more easily.
Rett Syndrome
19s (2015) S1 – S152
S147
estimated prevalence of RTT patients in Japan was 0.90 per 10,000 girls. It revealed the local clustering of hospitals, which provide the medical service for RTT patients. Interestingly, over 80% of five main symptoms appeared in typical RTT patients until 3 year-old. Conclusion: This is the first nationwide survey of RTT in Japan. It gave a prevalence of concomitant with previous studies in other countries. We have established the clinical and genetic database of Japanese RTT patients. Next, we have to use the database for clinical research to explore biological markers and treatment, with or without international collaborations.
P189 - 2279 Is the regression period in Rett syndrome well defined and easy to recognize? A.M. Bisgaard, M. Stahlhut, J.L. Larsen, B. Syhler, B. Schönewolf-Greulich. Centre for Rett syndrome, Department of Clinical Genetics – Kennedy Centre, Rigshospitalet, Copenhagen, Denmark Objective: In order to increase knowledge of regression as a clue to diagnose Rett syndrome (RTT), we want to investigate if the regression period (RP) is well defined and easy to recognize. Methods: Medical records (including questionnaires and interviews) were reviewed concerning the RP in children with clinical Rett syndrome and a MECP2 mutation referred to the nation-wide Centre for Rett syndrome in Denmark in the years 2012–2014. Results: Ten girls with RTT (8 typical/2 atypical) and a MECP2 mutation aged 1.7–5.3 years (mean 3.3 years; median 2.8 years) were referred to the centre and evaluated within 13–152 days (mean 58.3 days; median 41.5 days). Seven of the girls were post regression at this first evaluation. In the other 3 cases it was difficult to conclude but time showed that 2 girls were still in regression at the first visit. The girls were in RP in the range of about 4–35 months (mean 14.8 mo; median 12 mo). Before the RTT diagnosis 5 of the girls were referred to psychiatric evaluation at a time that turned out to be in the RP. One of these girls and 3 others had a muscular biopsy before (2), under (1) or after (1) an unrecognized RP. One girl had severe symptoms of epilepsy and adverse reactions to medication in RP. In 6 cases the RP along with other symptoms as handstereotypies led to suspicion of RTT. Five of the girls were diagnosed in the RP and the other 5 after the RP. Conclusion: In most of our cases, RP was not well defined or easily recognized. It might be overlooked because of its long and slow progression as well as co-morbidities like hypotonia or epilepsy. We conclude that more information regarding regression in RTT is needed to facilitate early diagnosis, counselling and treatment.
P191 - 2505 Two siblings with a CDKL5 mutation: Genotype and phenotype evaluation E.E.O. Hagebeuk, C.L. Marcelis, M. Alders, A. Kaspers, A.W. de Weerd. Department of Pediatric Neurology, Stichting Epilepsie Instellingen Nederland (SEIN), Zwolle, The Netherlands Objective: This is the second report of a family with a recurrence of a CDKL5 mutation (c. 283-3_290del) in two sisters. Their phenotype is different despite an identical genotype Clinically CDKL5 patients resemble those with Rett syndrome, caused by a MECP2 mutation, who experience a regression, after an initial normal development. However, CDKL5 patients experience a developmental delay from from birth onwards and seizures starts the first three months of life. Methods: Advanced genetic evaluations of the sisters and parents, the electropherogram, clinical and electroencephalographic (EEG) features of both sisters are discussed. Results: In the youngest patient, who was known to us prior to appearance of the clinical symptoms, neurological and EEG evaluations at the age of 6 weeks were normal. Infantile spasms evolved at the age of 10 weeks. Simultaneously, she showed a psychomotor regression and deterioration of the EEG into a severe epileptic pattern. Her older sister, was from the start severely hypotonic, had a developmental delay (without regression) and feeding problems and experiences seizures from the age of 8 weeks. In both seizures are refractory. The phenotype of the youngest sister is worse than that of her older sister, despite an identical genotype. This may be explained by differences in X-chromosomal inactivation and other unknown epigenetic and environmental factors. Unfortunately, X inactivation pattern could not be determined in the youngest sister. Both parents tested negative for the mutation in all tissues, but germline mosaicism is likely. Conclusion: This report of familial recurrence with suspected germline mosaicism in a healthy parent, has important consequences for genetic counselling. Although it is not possible to predict an exact recurrence risk, it is likely to be increased.
P190 - 2307 Epidemiological study of Japanese Rett syndrome M. Itoh, S. Nabatame, H. Tachimori, T. Matsuishi. National Center of Neurology and Psychiatry Objective: It has known that a prevalence of Rett syndrome (RTT) is approximately 1.0 per 10,000 females. However, we have never Japanese data. In 2010, the recent revised criterion for diagnosis of RTT was published. Here, we performed nationwide survey of RTT, according to the new criterion, to clarify the Japanese epidemiology of RTT. Methods: We selected 1,020 hospitals or institutes by stratified sampling from 2,918 ones specialized for pediatrics and pediatric neurology in Japan. We sent the first questionnaire to them to ask the number of RTT patients each institute followed from 2008 to 2009. After responded, we asked clinical details with the second questionnaire. Results: We received 677 responses from 1,020 hospitals (total response rate: 66.4%), and they counted 480 definite RTT patients and 79 atypical patients. The estimated total number of definite RTT patients was 1011 (95% confidential interval, 778–1244), and the
P192 - 2531 Overview of Rett syndrome associated with MECP2 mutation: Analysis of 7 patients I. Erol, S. Yetkinel, T. Savas. Associate Professor, Baskent University Faculty of Medicine, Department of Pediatrics, Neurology Division, Adana Teaching and Medical Research Center, Adana, Turkey Objective: The aim of the present study was to report our experience with Rett syndrome (RTT) associated with MECP2 mutation. Methods: Seven consecutive patients diagnosed with RTT associated with MECP2 mutation in our child neurology clinic were analyzed in terms of clinical findings retrospectively. Diagnosis were compared according to revised diagnostic criteria (2010) for RTT. Results: There were 7 girls, age range, 2.3 to 10.2 years. Age at the time of diagnosis were 2 to 5 years. Although 2 of the child had history of preterm birth. All of the patient had normal psychomotor development in first six months of life. Therefore none of the patient had any exclusion criteria. All of the