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Understanding preterm birth: Sjögren–Larsson Syndrome as a model
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 4 3 ee 4 4
Official Journal of the European Paediatric Neurology Society
Abstracts of EPNS 2017 e 12th European Paediatric Neurology Society Congress, 20e24 June 2017, Lyon, France POSTER PRESENTATIONS Wednesday, June 21 FOETAL NEUROLOGY P1-53 € greneLarsson Syndrome as a Understanding preterm birth: Sjo model P. Staps, J. Fuijkschot, M. Hogeveen, M.A.A.P. Willemsen. Department of Paediatric Neurology, Radboudumc, Nijmegen, The Netherlands Objective: Preterm birth is the world's leading cause of neonatal death and a major cause of cerebral palsy. The pathophysiological processes leading to preterm birth are limited known, while un€ greneLarsson derstanding is crucial in reducing preterm birth. Sjo Syndrome (SLS) is a rare, neurometabolic disease caused by fatty aldehyde dehydrogenase (FALDH) deficiency. FALDH is responsible for converting several fatty aldehydes to fatty acids, including breakdown of leukotriene B4 (LTB4). Patients with SLS suffer from ichthyosis, intellectual disability, spastic diplegia and retinopathy. We have previously shown, in a small series of 15 patients, that a majority of SLS patients is born preterm. Studying SLS might lead to insights in mechanisms causing preterm birth. Methods: To confirm our previous findings in a larger cohort, and to gain more knowledge about mechanisms leading to preterm birth, all known Dutch SLS patients and all cases reported in literature were analyzed. Results: Of 28 of 35 Dutch SLS patients the exact gestational age was known, 21 (75%) were born preterm, with a mean gestational age of 35.5 weeks (SD 2.2; p < 0.01 compared with normal Dutch population). In 16 found casereports, 69% was born preterm (mean of 35.2 weeks, SD 2.9). Conclusion: Preterm birth can be caused by premature activation of the hypothalamicepituitaryeadrenal axis, inflammatory responses, decidual bleeding and pathological uterine extension. Our hypothesis is that in SLS, children are born preterm because of increased fetal urinary secretion (in the amniotic fluid) of LTB4, which is a pro-inflammatory mediator. LTB4 concentrations are elevated since LTB4 is not broken down because of FALDH deficiency. This hypothesis is in line with the knowledge that inflammatory responses play a key role in the pathophysiology of preterm birth. As an orphan disease, SLS may contribute as a
1090-3798
model for one of the most common and urging problems of the unborn human.
http://dx.doi.org/10.1016/j.ejpn.2017.04.863 P1-54 Corpus callosum agenesis with clinically normal people caused by DCC mutations. Prenatal implication T. Billette de Villemeur, S. Valence, D. Heron, S. Heide, B. Keren, C. Nava, V. des Portes, C. Garel, E. Blondiaux, A. Afenjar, C. Mignot, A. Rastetter, C. Depienne, M.-L. Moutard. Department of Neuropaediatrics, Trousseau, AP-HP, GRC ConCer-LD, UPMC, Paris, France Corpus Callosum Agenesis (CCA) is a frequent brain malformation (1 per 4000 births), assumed to be responsible for 3e5% for intellectual disability (ID) in children. Nowadays, the diagnosis is often made during the ultrasound (US) follow-up of pregnancy. We recently published that mutations in DCC cause CCA, mirror movements (MM), or both, without intellectual disability (Marsh et al. Nature genetics, 2017 in press). We here report the clinical presentation of 23 persons mutated in six multigenerational families. The CCA was discovered twice fortuitously on the occasion of an MRI performed for a headache, nine time by systematic prenatal US, further confirmed by postnatal MRI, and one in a mother whose child was diagnosed during her pregnancy. In the 15 people who had a brain MRI, 7 had a complete and 4 a partial CCA; the last four had no CCA. Intellectual capacity was normal in the 15 adults who had a DCC mutation. All of them had unremarkable social, educational, professional and familial histories. The 8 children, age 2 and a half to 16, have normal development and school career. Three had mirror movements. Discussion CCA by itself does not imply ID. Neurologic developmental evolution of fetus with CCA discovered during pregnancy may be normal. We previously claim, as others, that it can be as frequent as 85% when the CAA is apparently isolated after complete prenatal explorations. Hence, the search for a DCC mutation should be added to improve the prognosis information given during pregnancy, to strengthen this favorable prognosis. In the case of prenatal CCA discovery, the search for a pathogenic causal mutation is an original and promising way to improve the uncertain prognosis of such a major cerebral malformation.
http://dx.doi.org/10.1016/j.ejpn.2017.04.864
Official Journal of the European Paediatric Neurology Society
Abstracts of EPNS 2017 e 12th European Paediatric Neurology Society Congress, 20e24 June 2017, Lyon, France POSTER PRESENTATIONS Wednesday, June 21 FOETAL NEUROLOGY P1-53 € greneLarsson Syndrome as a Understanding preterm birth: Sjo model P. Staps, J. Fuijkschot, M. Hogeveen, M.A.A.P. Willemsen. Department of Paediatric Neurology, Radboudumc, Nijmegen, The Netherlands Objective: Preterm birth is the world's leading cause of neonatal death and a major cause of cerebral palsy. The pathophysiological processes leading to preterm birth are limited known, while un€ greneLarsson derstanding is crucial in reducing preterm birth. Sjo Syndrome (SLS) is a rare, neurometabolic disease caused by fatty aldehyde dehydrogenase (FALDH) deficiency. FALDH is responsible for converting several fatty aldehydes to fatty acids, including breakdown of leukotriene B4 (LTB4). Patients with SLS suffer from ichthyosis, intellectual disability, spastic diplegia and retinopathy. We have previously shown, in a small series of 15 patients, that a majority of SLS patients is born preterm. Studying SLS might lead to insights in mechanisms causing preterm birth. Methods: To confirm our previous findings in a larger cohort, and to gain more knowledge about mechanisms leading to preterm birth, all known Dutch SLS patients and all cases reported in literature were analyzed. Results: Of 28 of 35 Dutch SLS patients the exact gestational age was known, 21 (75%) were born preterm, with a mean gestational age of 35.5 weeks (SD 2.2; p < 0.01 compared with normal Dutch population). In 16 found casereports, 69% was born preterm (mean of 35.2 weeks, SD 2.9). Conclusion: Preterm birth can be caused by premature activation of the hypothalamicepituitaryeadrenal axis, inflammatory responses, decidual bleeding and pathological uterine extension. Our hypothesis is that in SLS, children are born preterm because of increased fetal urinary secretion (in the amniotic fluid) of LTB4, which is a pro-inflammatory mediator. LTB4 concentrations are elevated since LTB4 is not broken down because of FALDH deficiency. This hypothesis is in line with the knowledge that inflammatory responses play a key role in the pathophysiology of preterm birth. As an orphan disease, SLS may contribute as a
1090-3798
model for one of the most common and urging problems of the unborn human.
http://dx.doi.org/10.1016/j.ejpn.2017.04.863 P1-54 Corpus callosum agenesis with clinically normal people caused by DCC mutations. Prenatal implication T. Billette de Villemeur, S. Valence, D. Heron, S. Heide, B. Keren, C. Nava, V. des Portes, C. Garel, E. Blondiaux, A. Afenjar, C. Mignot, A. Rastetter, C. Depienne, M.-L. Moutard. Department of Neuropaediatrics, Trousseau, AP-HP, GRC ConCer-LD, UPMC, Paris, France Corpus Callosum Agenesis (CCA) is a frequent brain malformation (1 per 4000 births), assumed to be responsible for 3e5% for intellectual disability (ID) in children. Nowadays, the diagnosis is often made during the ultrasound (US) follow-up of pregnancy. We recently published that mutations in DCC cause CCA, mirror movements (MM), or both, without intellectual disability (Marsh et al. Nature genetics, 2017 in press). We here report the clinical presentation of 23 persons mutated in six multigenerational families. The CCA was discovered twice fortuitously on the occasion of an MRI performed for a headache, nine time by systematic prenatal US, further confirmed by postnatal MRI, and one in a mother whose child was diagnosed during her pregnancy. In the 15 people who had a brain MRI, 7 had a complete and 4 a partial CCA; the last four had no CCA. Intellectual capacity was normal in the 15 adults who had a DCC mutation. All of them had unremarkable social, educational, professional and familial histories. The 8 children, age 2 and a half to 16, have normal development and school career. Three had mirror movements. Discussion CCA by itself does not imply ID. Neurologic developmental evolution of fetus with CCA discovered during pregnancy may be normal. We previously claim, as others, that it can be as frequent as 85% when the CAA is apparently isolated after complete prenatal explorations. Hence, the search for a DCC mutation should be added to improve the prognosis information given during pregnancy, to strengthen this favorable prognosis. In the case of prenatal CCA discovery, the search for a pathogenic causal mutation is an original and promising way to improve the uncertain prognosis of such a major cerebral malformation.
http://dx.doi.org/10.1016/j.ejpn.2017.04.864