- Email: [email protected]
P305 – 2007 A male with mild intellectual disability and hyperckemia
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
periventricular white matter abnormalities, ventriculomegaly, pontocerebellar hypoplasia and multiple cerebellar cysts. Regarding genetic study, one patient (5%) had homozygous POMT1 mutation, three patients (15%) had homozygous Fukutin mutation and twelve patients (63%) had homozygous POMGNT1 mutation. In the collagen VI deficiency group, the most common findings were developmental motor retardation, contractures, distal hyperlaxicity and respiratory deficiency Conclusion: Congenital muscular dystrophy with defective dystroglycan glycosylation and collagen VI deficiency should be kept in mind in cases with combined eye and brain malformations, developmental motor retardation, contractures and distal hyperlaxicity.
P303 - 1565 The pseudo-poliomyelitis of the 21st century Teoh H, Sampaio H. Sydney Children’s Hospital, Randwick, NSW, Australia – [email protected] It has been 12 years since enterovirus 71 haunted the hallways of our hospital, with 18 of 200 children affected experiencing neurologic complications. Between Jan 2013 to March 2013, 30 children presented with neurologic symptoms and enterovirus positivity on faeces, throat swab, serum or CSF. 14 out of the 30 were genotyped and found to have enterovirus 71. Of the 18 patients who had an MRI scan, two thirds showed an abnormality with increased T2 signal intensity in the brainstem +/- spinal cord involvement seen. Symptoms of these patients were varied and included: neurogenic pulmonary oedema with quadriparesis, seizures, myoclonic jerks (almost invariable), monoplegia, unilateral cranial nerve 6 palsy, generalised weakness, irritability and neurogenic bladder. Treatment was also variable with 3 needing full cardio-respiratory support with intravenous immunoglobulin (IVIG) and high dose methylprednisolone, 4 receiving IVIG and high dose methylprednisolone, 4 receiving only high dose methylprednisolone and 4 receiving only IVIG and 15 receiving no special treatment. 29 children improved in their clinical course. All patients presenting with limb weakness, although improved, continue to have residual weakness at follow up in the presence of a normal MRI, regardless of treatment. Follow up is on-going.
17s (2013) S1 – S149
S137
emphasizes that autoimmune disease is a recurrent feature of the Xp11.2 duplication syndrome, which should be considered in the follow-up of these patients. The exact mechanism underlying this autoimmune propensity remains to be elucidated.
P305 - 2007 A male with mild intellectual disability and hyperckemia López Pisón J, Monge Galindo L, Torres JA, Rodríguez Valle A, García Jiménez MªC, Peña Segura JL. Hospital Universitario Miguel Servet, Zaragoza, Spain – [email protected] Danon disease is a rare X-linked dominant disorder caused by primary deficiency of lysosome-associated membrane protein-2 (LAMP-2) characterized by cardiomyopathy, myopathy, and variable mental retardation. We present a case of a boy and his mother with Danon disease. An 11-year-old boy with mild intellectual disability and increase of CK, ranging between 400 and 960. X-fragile and Steinert genetic studies normal. His mother underwent a heart transplant after a postpartum cardiomyopathy. Our study protocol of hiperCKemia, without etiologic diagnosis, required a muscle biopsy, that showed autophagic vacuolar myopathy and no detectable LAMP-2 in immunohistochemistry analyses. The genetic study identified a mutation A314GfsX2 in exon 8 of the LAMP2 gene, in the boy and his mother (with normal CK levels and intelligence). The only sister has no mutation. Danon disease is a rare disorder with substantial morbidity and early mortality due to arrhythmia and cardiomyopathy. Male patients usually suffer severe cardiomyopathy, mild myopathy and mental retardation. Men have a high morbidity rate and are unlikely to reach the age of 25 years without a cardiac transplantation. Women are less severely affected but have higher than expected levels of cognitive and skeletal muscle complaints and manifest an equal prevalence of dilated cardiomyopathy and hypertrophic cardiomyopathy. We highlight the importance of studying hyperCKemia, the need for cardiac surveillance in different muscle diseases and the importance of concern for muscle disease in families with cardiomyopathy, due to the implications of diagnosis, management, prognosis and genetic advice.
P306 - 9999 P304 - 1516 Lambert-Eaton myasthenic syndrome in a 13-year-old girl with Xp11.22-p11.23 duplication Verbeek S, Vanakker O, Mercelis R, Haerynck F, Dullaers M, Van Coster R, Verhelst H. University Hospital Ghent, Belgium – [email protected] Lambert-Eaton myasthenic syndrome (LEMS) is a presynaptic autoimmune disease of the neuromuscular junction typically seen in adults as a paraneoplastic syndrome. Only rare cases have been reported in childhood. In most childhood cases, malignancies have not been detected and an underlying propensity to autoimmune disease is suspected. Nevertheless, little is known about genetic factors that may contribute to the susceptibility of an individual to develop LEMS. We report on a 13-year-old girl, known with the Xp11.22-p11.23 duplication syndrome, who presented with severe non-neoplastic LEMS. The potential role of this microduplication syndrome in development of LEMS is explored. Literature review of twelve patients with Xp11.2 duplication syndrome showed that three of them suffered from various autoimmune diseases. The common duplicated region in those three patients and the presented case comprises 12 disease associated genes including the FOXP3 (Forkhead Box P3) gene and the WAS (Wiskott-Aldrich syndrome) gene, both implicated in immune function. However, it is unclear whether increased gene dosage of one or both genes can cause susceptibility to autoimmune diseases. In conclusion, the presented case
A positive Gowers sign mimicking a primairy neuromuscular disorder for 17 years. de Rijk-van Andel JF, de Coo IFM, van der Laar I. Erasmus Medical Center, Rotterdam, the Netherlands Niels was born in september 1989 after a normal pregnancy and delivery from Dutch non-consanguineous parents. His two older sisters are healthy. In his family there are no neuromuscular diseases. His development was normal until the age of 3 years, when he developed walkingproblems and a positive Gowers sign. An intensive neuromuscular work-up in three academic centres with muscle biopsy and DNA analysis followed, but did not show any specific disorder. Symptoms suggested a SMA type III, but no deletion was ever found in the DNA analysis. At the age of 20 years he complained of pain in his leggs. On examination the circumference of the upper leggs were the same as the circumference of the lower leggs. Then an X-ray of the bone showed bone dysplasia. Finally, the diagnosis CamuratiEngelmann (CED) was confirmed by the clinical genetics. There is a c.652C>T mutation in the TGFB1-gene. This is he coding gene for the transforming growthfactor TGFb1. In the symptoms of CED muscle weakness is described in about 1/3 of the patients due to a high TGFb1 activity which inhibits muscle and fat development. The biggest challenge of the moment is the pain treatment.
periventricular white matter abnormalities, ventriculomegaly, pontocerebellar hypoplasia and multiple cerebellar cysts. Regarding genetic study, one patient (5%) had homozygous POMT1 mutation, three patients (15%) had homozygous Fukutin mutation and twelve patients (63%) had homozygous POMGNT1 mutation. In the collagen VI deficiency group, the most common findings were developmental motor retardation, contractures, distal hyperlaxicity and respiratory deficiency Conclusion: Congenital muscular dystrophy with defective dystroglycan glycosylation and collagen VI deficiency should be kept in mind in cases with combined eye and brain malformations, developmental motor retardation, contractures and distal hyperlaxicity.
P303 - 1565 The pseudo-poliomyelitis of the 21st century Teoh H, Sampaio H. Sydney Children’s Hospital, Randwick, NSW, Australia – [email protected] It has been 12 years since enterovirus 71 haunted the hallways of our hospital, with 18 of 200 children affected experiencing neurologic complications. Between Jan 2013 to March 2013, 30 children presented with neurologic symptoms and enterovirus positivity on faeces, throat swab, serum or CSF. 14 out of the 30 were genotyped and found to have enterovirus 71. Of the 18 patients who had an MRI scan, two thirds showed an abnormality with increased T2 signal intensity in the brainstem +/- spinal cord involvement seen. Symptoms of these patients were varied and included: neurogenic pulmonary oedema with quadriparesis, seizures, myoclonic jerks (almost invariable), monoplegia, unilateral cranial nerve 6 palsy, generalised weakness, irritability and neurogenic bladder. Treatment was also variable with 3 needing full cardio-respiratory support with intravenous immunoglobulin (IVIG) and high dose methylprednisolone, 4 receiving IVIG and high dose methylprednisolone, 4 receiving only high dose methylprednisolone and 4 receiving only IVIG and 15 receiving no special treatment. 29 children improved in their clinical course. All patients presenting with limb weakness, although improved, continue to have residual weakness at follow up in the presence of a normal MRI, regardless of treatment. Follow up is on-going.
17s (2013) S1 – S149
S137
emphasizes that autoimmune disease is a recurrent feature of the Xp11.2 duplication syndrome, which should be considered in the follow-up of these patients. The exact mechanism underlying this autoimmune propensity remains to be elucidated.
P305 - 2007 A male with mild intellectual disability and hyperckemia López Pisón J, Monge Galindo L, Torres JA, Rodríguez Valle A, García Jiménez MªC, Peña Segura JL. Hospital Universitario Miguel Servet, Zaragoza, Spain – [email protected] Danon disease is a rare X-linked dominant disorder caused by primary deficiency of lysosome-associated membrane protein-2 (LAMP-2) characterized by cardiomyopathy, myopathy, and variable mental retardation. We present a case of a boy and his mother with Danon disease. An 11-year-old boy with mild intellectual disability and increase of CK, ranging between 400 and 960. X-fragile and Steinert genetic studies normal. His mother underwent a heart transplant after a postpartum cardiomyopathy. Our study protocol of hiperCKemia, without etiologic diagnosis, required a muscle biopsy, that showed autophagic vacuolar myopathy and no detectable LAMP-2 in immunohistochemistry analyses. The genetic study identified a mutation A314GfsX2 in exon 8 of the LAMP2 gene, in the boy and his mother (with normal CK levels and intelligence). The only sister has no mutation. Danon disease is a rare disorder with substantial morbidity and early mortality due to arrhythmia and cardiomyopathy. Male patients usually suffer severe cardiomyopathy, mild myopathy and mental retardation. Men have a high morbidity rate and are unlikely to reach the age of 25 years without a cardiac transplantation. Women are less severely affected but have higher than expected levels of cognitive and skeletal muscle complaints and manifest an equal prevalence of dilated cardiomyopathy and hypertrophic cardiomyopathy. We highlight the importance of studying hyperCKemia, the need for cardiac surveillance in different muscle diseases and the importance of concern for muscle disease in families with cardiomyopathy, due to the implications of diagnosis, management, prognosis and genetic advice.
P306 - 9999 P304 - 1516 Lambert-Eaton myasthenic syndrome in a 13-year-old girl with Xp11.22-p11.23 duplication Verbeek S, Vanakker O, Mercelis R, Haerynck F, Dullaers M, Van Coster R, Verhelst H. University Hospital Ghent, Belgium – [email protected] Lambert-Eaton myasthenic syndrome (LEMS) is a presynaptic autoimmune disease of the neuromuscular junction typically seen in adults as a paraneoplastic syndrome. Only rare cases have been reported in childhood. In most childhood cases, malignancies have not been detected and an underlying propensity to autoimmune disease is suspected. Nevertheless, little is known about genetic factors that may contribute to the susceptibility of an individual to develop LEMS. We report on a 13-year-old girl, known with the Xp11.22-p11.23 duplication syndrome, who presented with severe non-neoplastic LEMS. The potential role of this microduplication syndrome in development of LEMS is explored. Literature review of twelve patients with Xp11.2 duplication syndrome showed that three of them suffered from various autoimmune diseases. The common duplicated region in those three patients and the presented case comprises 12 disease associated genes including the FOXP3 (Forkhead Box P3) gene and the WAS (Wiskott-Aldrich syndrome) gene, both implicated in immune function. However, it is unclear whether increased gene dosage of one or both genes can cause susceptibility to autoimmune diseases. In conclusion, the presented case
A positive Gowers sign mimicking a primairy neuromuscular disorder for 17 years. de Rijk-van Andel JF, de Coo IFM, van der Laar I. Erasmus Medical Center, Rotterdam, the Netherlands Niels was born in september 1989 after a normal pregnancy and delivery from Dutch non-consanguineous parents. His two older sisters are healthy. In his family there are no neuromuscular diseases. His development was normal until the age of 3 years, when he developed walkingproblems and a positive Gowers sign. An intensive neuromuscular work-up in three academic centres with muscle biopsy and DNA analysis followed, but did not show any specific disorder. Symptoms suggested a SMA type III, but no deletion was ever found in the DNA analysis. At the age of 20 years he complained of pain in his leggs. On examination the circumference of the upper leggs were the same as the circumference of the lower leggs. Then an X-ray of the bone showed bone dysplasia. Finally, the diagnosis CamuratiEngelmann (CED) was confirmed by the clinical genetics. There is a c.652C>T mutation in the TGFB1-gene. This is he coding gene for the transforming growthfactor TGFb1. In the symptoms of CED muscle weakness is described in about 1/3 of the patients due to a high TGFb1 activity which inhibits muscle and fat development. The biggest challenge of the moment is the pain treatment.