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P136 – 2961: A review of a paediatric cases of multiple sclerosis in an Irish tertiary referral centre
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EUROPEAN JOURNAL O F PAEDIATRIC NEUROLOGY
P135 - 2956 Prader-Willi syndrome, not so rare among the floppy infants S. Blichfeldt. Paediatric Department, Herlev University Hospital, 2730 Herlev, Denmark Objective: Prader-Willi syndrome (PWS) is one of the more common causes of severe neonatal hypotonia. PWS is seen in 1:15000 newborn. The clinical picture is characteristic and different to that of neuromuscular and metabolic diseases. Early diagnoses is important for treatment. During childhood and adulthood several symptoms will arise, and knowledge about PWS is important for management and survival. Methods: Genetics and clinical picture are described. Results: In PWS paternal genetic information from chromosome 15q is missing, either as paternal deletion 15q, maternal uniparental disomia (UPD) of chromosome 15, or by an imprinting mutation on paternal 15q. PWS can be confirmed by a DNA methylation test. Del 15q (ca. 65% of cases) is detected by an array CGH test. In pregnancy reduced foetal movements, oligo or poly hydramnion can be seen. At birth breech presentation is common. Apgar score is often normal, but followed by severe hypotonia. The child sleeps, does not cry, is not interested in eating or sucking. Breathing is normal. Tube feeding is necessary in weeks or months. Slight dysmorphism ban be seen: Small bifrontal diameter, almond shaped eyes, micrognathia, open triangular mouth, small hands and feet. 95% of boys have cryptorchism. The motor function gradually improves, milestones are delayed. From age 1–2 years a peculiar interest for food and eating arises followed by a morbid obesity, but only if food is not controlled. Growth hormone deficiency, hypogonadism, abnormal temperature regulation, abnormal sleep pattern, sleep apnea, scolioses, behavioural problems and mild to moderate mental retardation are characteristic. Psychiatric diseases are seen in adults. Conclusion: Early diagnose is important and possible. Many clinical symptoms can be treated successfully to secure quality of life for patients and family. Especially it is possible, to prevent severe overweight and obesity related diseases including early death.
P136 - 2961 A review of a paediatric cases of multiple sclerosis in an Irish tertiary referral centre H. Fitzpatrick, N. Enright, B. Lynch. Department of Neurology, Temple St Children’s University Hospital, Dublin, Ireland To examine a cohort of paediatric multiple sclerosis (MS) patients in an Irish tertiary paediatric neurology referral centre with emphasis on presentation, investigations and management, comparing to other described cohorts. Methods: Patients were identified through department records, with chart review performed to obtain clinical details. Laboratory and radiological information was reviewed. Results: Nine patients presented to the department over a 6 year period (3.5–15 yo). Female to male ratio was 2:1 with all patients of western European ethnicity. They presented 77% with brainstem syndromes, including visual problems (55%), sensory disturbance (44%), dizziness or ataxia (22%), reduced power or a cranial nerve palsy in 11%. Headache was a co-existing feature in 66%. One patient had no defining event but rather incidental findings on an MRI Brain. Family history was significant for MS (22%) and autoimmune condition (22%). Initial MRI brain shower cerebellar demyelinating lesions in 77% and spinal lesions in 55%. Oligoclonal bands were checked in all patients and positive in 66% with NMO antibodies checked in 66% which were negative. Clinical relapses occurred in 66% with a mean time to relapse 11 months. Steroids were commenced in 77% of patients in acute phase, with one patient commencing interferon beta 1a started directly from steroids due to ongoing symptoms. As maintenance treatment, interferon-beta-1a was started in all patients who relapsed or had deterioration in fol-
19s (2015) S1 – S152
low up imaging, with 2 progressing to fingolimod due to failed treatment. Two patients required no treatment due to either no symptoms or relapses. Conclusion: Our patient study reflected previous described patient cohorts especially in their presentations, investigations and relapsing-remitting course [1,2]. Our female to male ratio was lower than previously described [1]. We also had high rates of positive family history of both autoimmune disease and Multiple sclerosis. Treatment for these patients followed international guidelines [3].
P137 - 2976 Two cases of Noonan syndrome: Genotype–phenotype correlation M. De Rademaeker, A. Jansen, I. Gies, G. Matthijs, B. Caljon, K. Stouffs, K. Keymolen. Centre for Medical Genetics, Reproduction and Genetics, Reproduction Genetics and Regenerative Medicine, Vrije Universiteit Brussel (VUB), UZ Brussel, Brussel, Belgium Objective: Noonan syndrome is the most common Rasopathy, characterised by typical facial dysmorphism (hypertelorism, downslanting palpebral fissures, ptosis, low-set posteriorly rotated ears) and congenital heart defects. Other features include short stature, cryptorchidism, ectodermal abnormalities, intellectual impairment. The phenotype is variable. The disease is caused by mutations in genes encoding proteins interacting with the Ras-MAPK signaling pathway. How the clinical phenotype can orient the molecular analysis will be further illustrated with two patients. Methods: Clinical and molecular data on two patients within the Noonan spectrum are presented. Results: The first patient, a boy born with normal birth parameters, after pregnancy complicated by polyhydramnios. He presented typical dysmorphism, pectus excavatum and bilateral cryptorchidism. Billowing of the mitral valve was seen at cardiac evaluation. Evolution showes a relative macrocephaly and curly hair. Stature and psychomotor development are normal. Molecular analysis of the PTPN11 gene showed no mutations. Further analysis showed not earlier reported mutation in the SOS1 gene (c.1670_1687del). The second patient, a boy born with a birthweigth above the 95th centile, presented with typical dysmorphism, macrocephaly and atrial septal defect. Evolution shows slow growing, sparse, thin hair, pectus excavatum and severe eczema. He has short stature and intellectual disability. Molecular analysis of the most common genes in the RAS-MAPK pathway didn’t reveal any mutation. Recently a mutation was found in the SHOC2 gene (p.Ser2Gly). Conclusion: Noonan spectrum is a genetically heterogenous disorder but some distinctive characteristics are associated with particular genes as illustrated in our cases. SOS1 mutations are often associated with normal stature and normal cognition. Recently a recurrent mutation (p.Ser2Gly)in the SHOC2 gene has been associated with with loose anagen hair, short stature and more pronounced intellectual impairment. Knowledge of the phenotype–genotype correlation is helpful in clinical management and in choosing the best molecular tests.
P138 - 3000 Neonatal brachial plexus palsy – Romanian single centre experience over 6 years D. Craiu, A. Dica, D. Barca, O. Tarta-Arsene, I. Minciu, C. Iliescu, C. Burloiu, N. Butoianu, M. Budisteanu, C. Pomeran, C. Sandu, R. Gherghiceanu, L. Robanescu, D. Zamfirescu. Pediatric Neurology Clinic, “Alexandru Obregia” Clinical Psychiatric Hospital, Bucharest, Romania; “Carol Davila” University of Medicine Bucharest, Department of Neurology, Pediatric Neurology, Psychiatry, Neurosurgery; Discipline Pediatric Neurology Objective: The aim of this poster is to analyze the cohort of patients with NBPP followed in the Pediatric Neurology Department,
EUROPEAN JOURNAL O F PAEDIATRIC NEUROLOGY
P135 - 2956 Prader-Willi syndrome, not so rare among the floppy infants S. Blichfeldt. Paediatric Department, Herlev University Hospital, 2730 Herlev, Denmark Objective: Prader-Willi syndrome (PWS) is one of the more common causes of severe neonatal hypotonia. PWS is seen in 1:15000 newborn. The clinical picture is characteristic and different to that of neuromuscular and metabolic diseases. Early diagnoses is important for treatment. During childhood and adulthood several symptoms will arise, and knowledge about PWS is important for management and survival. Methods: Genetics and clinical picture are described. Results: In PWS paternal genetic information from chromosome 15q is missing, either as paternal deletion 15q, maternal uniparental disomia (UPD) of chromosome 15, or by an imprinting mutation on paternal 15q. PWS can be confirmed by a DNA methylation test. Del 15q (ca. 65% of cases) is detected by an array CGH test. In pregnancy reduced foetal movements, oligo or poly hydramnion can be seen. At birth breech presentation is common. Apgar score is often normal, but followed by severe hypotonia. The child sleeps, does not cry, is not interested in eating or sucking. Breathing is normal. Tube feeding is necessary in weeks or months. Slight dysmorphism ban be seen: Small bifrontal diameter, almond shaped eyes, micrognathia, open triangular mouth, small hands and feet. 95% of boys have cryptorchism. The motor function gradually improves, milestones are delayed. From age 1–2 years a peculiar interest for food and eating arises followed by a morbid obesity, but only if food is not controlled. Growth hormone deficiency, hypogonadism, abnormal temperature regulation, abnormal sleep pattern, sleep apnea, scolioses, behavioural problems and mild to moderate mental retardation are characteristic. Psychiatric diseases are seen in adults. Conclusion: Early diagnose is important and possible. Many clinical symptoms can be treated successfully to secure quality of life for patients and family. Especially it is possible, to prevent severe overweight and obesity related diseases including early death.
P136 - 2961 A review of a paediatric cases of multiple sclerosis in an Irish tertiary referral centre H. Fitzpatrick, N. Enright, B. Lynch. Department of Neurology, Temple St Children’s University Hospital, Dublin, Ireland To examine a cohort of paediatric multiple sclerosis (MS) patients in an Irish tertiary paediatric neurology referral centre with emphasis on presentation, investigations and management, comparing to other described cohorts. Methods: Patients were identified through department records, with chart review performed to obtain clinical details. Laboratory and radiological information was reviewed. Results: Nine patients presented to the department over a 6 year period (3.5–15 yo). Female to male ratio was 2:1 with all patients of western European ethnicity. They presented 77% with brainstem syndromes, including visual problems (55%), sensory disturbance (44%), dizziness or ataxia (22%), reduced power or a cranial nerve palsy in 11%. Headache was a co-existing feature in 66%. One patient had no defining event but rather incidental findings on an MRI Brain. Family history was significant for MS (22%) and autoimmune condition (22%). Initial MRI brain shower cerebellar demyelinating lesions in 77% and spinal lesions in 55%. Oligoclonal bands were checked in all patients and positive in 66% with NMO antibodies checked in 66% which were negative. Clinical relapses occurred in 66% with a mean time to relapse 11 months. Steroids were commenced in 77% of patients in acute phase, with one patient commencing interferon beta 1a started directly from steroids due to ongoing symptoms. As maintenance treatment, interferon-beta-1a was started in all patients who relapsed or had deterioration in fol-
19s (2015) S1 – S152
low up imaging, with 2 progressing to fingolimod due to failed treatment. Two patients required no treatment due to either no symptoms or relapses. Conclusion: Our patient study reflected previous described patient cohorts especially in their presentations, investigations and relapsing-remitting course [1,2]. Our female to male ratio was lower than previously described [1]. We also had high rates of positive family history of both autoimmune disease and Multiple sclerosis. Treatment for these patients followed international guidelines [3].
P137 - 2976 Two cases of Noonan syndrome: Genotype–phenotype correlation M. De Rademaeker, A. Jansen, I. Gies, G. Matthijs, B. Caljon, K. Stouffs, K. Keymolen. Centre for Medical Genetics, Reproduction and Genetics, Reproduction Genetics and Regenerative Medicine, Vrije Universiteit Brussel (VUB), UZ Brussel, Brussel, Belgium Objective: Noonan syndrome is the most common Rasopathy, characterised by typical facial dysmorphism (hypertelorism, downslanting palpebral fissures, ptosis, low-set posteriorly rotated ears) and congenital heart defects. Other features include short stature, cryptorchidism, ectodermal abnormalities, intellectual impairment. The phenotype is variable. The disease is caused by mutations in genes encoding proteins interacting with the Ras-MAPK signaling pathway. How the clinical phenotype can orient the molecular analysis will be further illustrated with two patients. Methods: Clinical and molecular data on two patients within the Noonan spectrum are presented. Results: The first patient, a boy born with normal birth parameters, after pregnancy complicated by polyhydramnios. He presented typical dysmorphism, pectus excavatum and bilateral cryptorchidism. Billowing of the mitral valve was seen at cardiac evaluation. Evolution showes a relative macrocephaly and curly hair. Stature and psychomotor development are normal. Molecular analysis of the PTPN11 gene showed no mutations. Further analysis showed not earlier reported mutation in the SOS1 gene (c.1670_1687del). The second patient, a boy born with a birthweigth above the 95th centile, presented with typical dysmorphism, macrocephaly and atrial septal defect. Evolution shows slow growing, sparse, thin hair, pectus excavatum and severe eczema. He has short stature and intellectual disability. Molecular analysis of the most common genes in the RAS-MAPK pathway didn’t reveal any mutation. Recently a mutation was found in the SHOC2 gene (p.Ser2Gly). Conclusion: Noonan spectrum is a genetically heterogenous disorder but some distinctive characteristics are associated with particular genes as illustrated in our cases. SOS1 mutations are often associated with normal stature and normal cognition. Recently a recurrent mutation (p.Ser2Gly)in the SHOC2 gene has been associated with with loose anagen hair, short stature and more pronounced intellectual impairment. Knowledge of the phenotype–genotype correlation is helpful in clinical management and in choosing the best molecular tests.
P138 - 3000 Neonatal brachial plexus palsy – Romanian single centre experience over 6 years D. Craiu, A. Dica, D. Barca, O. Tarta-Arsene, I. Minciu, C. Iliescu, C. Burloiu, N. Butoianu, M. Budisteanu, C. Pomeran, C. Sandu, R. Gherghiceanu, L. Robanescu, D. Zamfirescu. Pediatric Neurology Clinic, “Alexandru Obregia” Clinical Psychiatric Hospital, Bucharest, Romania; “Carol Davila” University of Medicine Bucharest, Department of Neurology, Pediatric Neurology, Psychiatry, Neurosurgery; Discipline Pediatric Neurology Objective: The aim of this poster is to analyze the cohort of patients with NBPP followed in the Pediatric Neurology Department,