Evren GÜMÜŞ, Beyhan DURAK ARAS, Oğuz ÇİLİNGİR, Coşkun YARAR, Kürşat Bora ÇARMAN, Sibel LAÇİNER GÜRLEVİK, Ozan KOÇAK, Sevilhan ARTAN

Apolipoprotein E allelic variants and cerebral palsy

Cerebral palsy (CP) is the most frequent cause of mobility restriction andposture disturbance in childhood. Against the complexity in disease etiology,genetic factors, including Apolipoprotein E allelic distribution in this patientpopulation, are worthy targets for investigation. ApoE is a lipoprotein ofcentral nervous system encoded by ApoE gene with its 3 main co-dominantalleles, 2, 3 and 4. We aimed to evaluate the allelic frequencies of ApoE geneand its association with coexisting clinical entities such as vision and hearingimpairment, cognitive problems, seizures and MRI findings in a pediatricpatient population native to middle Anatolian region. Seventy-eight childrenwith CP and 60 healthy controls were genotyped. Genotypic variations alongwith coexisting clinical conditions and CP-related medical findings werecompared between the patient and control groups. The Denver DevelopmentalScreening Test for all, the Wechsler Intelligence Scale for Children-IV (shortform WISC-IV; Turkish version) for the patients >6y and the Stanford–BinetIntelligence Scale (SB-5) for those who aged 2-6 years old were employed toevaluate cognitive and mental abilities of the patients. ApoE 2 and 4 alleleswere more frequent in the patient group (p

PDF

___

1. Rosenbaum P, Paneth N, Leviton A, et al. A report: The definition and classification of cerebral palsy April 2006. Dev Med Child Neurol Suppl 2007; 109: 8-14.

2. Van Naarden Braun K, Doernberg N, Schieve L, Christensen D, Goodman A, Yeargin-Allsopp M. Birth Prevalence of Cerebral Palsy: A Population-Based Study. Pediatrics 2016; 137. doi: 10.1542/peds.2015-2872.

3. Himmelmann K, Uvebrant P. The panorama of cerebral palsy in Sweden. XI. Changing patterns in the birth-year period 2003-2006. Acta Paediatr 2014; 103: 618-624.

4. Aydin R. Serebral palsi epidemiyolojisi. Türkiye Klinikleri Fiziksel Tıp ve Rehabilitasyon Dergisi Özel Sayısı 2009; 2: 1-7.

5. Erkin G, Delialioglu SU, Ozel S, Culha C, Sirzai H. Risk factors and clinical profiles in Turkish children with cerebral palsy: Analysis of 625 cases. Int J Rehabil Res 2008; 31: 89-91.

6. Badawi N, Keogh JM. Causal pathways in cerebral palsy. J Paediatr Child Health 2013; 49: 5-8.

7. Numata Y, Onuma A, Kobayashi Y, et al. Brain magnetic resonance imaging and motor and intellectual functioning in 86 patients born at term with spastic diplegia. Dev Med Child Neurol 2013; 55: 167-172.

8. Himmelmann K, Hagberg G, Uvebrant P. The changing panorama of cerebral palsy in Sweden. X. Prevalence and origin in the birth-year period 1999-2002. Acta Paediatr 2010; 99: 1337-1343.

9. MacLennan AH, Thompson SC, Gecz J. Cerebral palsy: Causes, pathways, and the role of genetic variants. Am J Obstet Gynecol 2015; 213: 779-788.

10. Costeff H. Estimated frequency of genetic and nongenetic causes of congenital idiopathic cerebral palsy in west Sweden. Ann Hum Genet 2004; 68(Pt 5): 515-520.

11. Fahey MC, Maclennan AH, Kretzschmar D, Gecz C, Kruer MC. The genetic basis of cerebral palsy. Dev Med Child Neurol 2017; 59: 462-469.

12. Oskoui M, Gazzellone MJ, Thiruvahindrapuram B, et al. Clinically relevant copy number variations detected in cerebral palsy. Nat Commun 2015; 6: 7949.

13. Wu D, Zou YF, Xu XY, et al. The association of genetic polymorphisms with cerebral palsy: A meta-analysis. Dev Med Child Neurol 2011; 53: 217-225.

14. Cedazo-Mínguez A. Apolipoprotein E and Alzheimer’s disease: Molecular mechanisms and therapeutic opportunities. J Cell Mol Med 2007; 11: 1227-1238.

15. Mahley RW, Weisgraber KH, Huang Y. Apolipoprotein E4: A causative factor and therapeutic target in neuropathology, including Alzheimer’s disease. Proc Natl Acad Sci U.S.A 2006; 103: 5644-5651.

16. Ponsford J, McLaren A, Schönberger M, et al. The association between apolipoprotein E and traumatic brain injury severity and functional outcome in a rehabilitation sample. J Neurotrauma 2011; 28: 1683- 1692.

17. Sriram S, Rodriguez M. Indictment of the microglia as the villain in multiple sclerosis. Neurology 1997; 48: 464-470.

18. Winter S, Autry A, Boyle C, Yeargin-Allsopp M. Trends in the prevalence of cerebral palsy in a populationbased study. Pediatrics 2002; 110: 1220-1225.

19. de Kieviet JF, Zoetebier L, van Elburg RM, Vermeulen RJ, Oosterlaan J. Brain development of very preterm and very low-birthweight children in childhood and adolescence: A meta-analysis. Dev Med Child Neurol 2012; 54: 313-323.

20. Haldipur P, Bharti U, Alberti C, et al. Preterm delivery disrupts the developmental program of the cerebellum. PLoS One 2011; 6: e23449.

21. Greisen G. To autoregulate or not to autoregulate-that is no longer the question. Semin Pediatr Neurol 2009; 16: 207-215.

22. Korja M, Ylijoki M, Lapinleimu H, et al. Apolipoprotein E, brain injury and neurodevelopmental outcome of children. Genes Brain Behav 2013; 12: 348-352.

23. Norda S, Rausch TK, Orlikowsky T, et al. Apolipoprotein E genotype in very preterm neonates with intrauterine growth restriction: An analysis of the German Neonatal Network Cohort. Biomed Res Int 2017; 2017: 2837027.

24. Laskowitz DT, Horsburgh K, Roses AD. Apolipoprotein E and the CNS response to injury. J Cereb Blood Flow Metab 1998; 18: 465-471

25 Lien E, Andersen GL, Bao Y, et al. Apolipoprotein E polymorphisms and severity of cerebral palsy: A cross-sectional study in 255 children in Norway. Dev Med Child Neurol 2013; 55: 372-377.

26. Xu Y, Wang H, Sun Y, et al. The association of apolipoprotein E gene polymorphisms with cerebral palsy in Chinese infants. Mol Genet Genomics 2014; 289: 411-416.

27. Stoknes M, Lien E, Andersen GL, et al. Child apolipoprotein E gene variants and risk of cerebral palsy: Estimation from case–parent triads. Eur J Paediatr Neurol2015; 19: 286-291.

28. Washburn LK, Dillard RG, Goldstein DJ, Klinepeter KL, deRegnier RA, O'Shea TM. Survival and major neurodevelopmental impairment in extremely low gestational age newborns born 1990-2000: A retrospective cohort study. BMC Pediatr 2007; 7:20.

29. Christine C, Dolk H, Platt MJ, Colver A, Prasauskiene A, Krägeloh-Mann I; SCPE Collaborative Group. Recommendations from the SCPE collaborative group for defining and classifying cerebral palsy. Dev Med Child Neurol Suppl 2007; 109: 35-38.

30. Palisano R, Rosenbaum P, Walter S, Russell D, Wood E, Galuppi B. Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev Med Child Neurol 1997; 39: 214-223.

31. Crawford JR, Anderson V, Rankin PM, Macdonald J. An index-based short-form of the WISC-IV with accompanying analysis of the reliability and abnormality of differences. Br J Clin Psychol 2010; 49(Pt 2): 235- 258.

32. Yin Foo R, Guppy M, Johnston LM. Intelligence assessments for children with cerebral palsy: A systematic review. Dev Med Child Neurol 2013; 55: 911-918.

33. Johnson A, Perinatal N, Unit E, Road O. Prevalence and characteristics of children with cerebral palsy in Europe. Dev Med Child Neurol 2002; 44: 633-640.

34.Ones K, Celik B, Caglar N, Gultekin O, Yılmaz E, Cetinkaya B. Serebralpalsi polikliniğine müracaat eden hastaların demo grafik ve klinik özellikleri. Türkiye Fiziksel Tıp ve Rehabilitasyon Dergisi 2008; 54: 13-16.

35. Topp M, Uldall P, Greisen G. Cerebral palsy births in eastern Denmark, 1987-90: Implications for neonatal care. Paediatr Perinat Epidemiol2001; 15: 271-277.

36. Ipek B, Ecevit C, Ipek I, Kocabas O, Kavaklı T, Ozturk A. The evaluation of 371 cases with cerebral palsy between January 1984 and December 2004. J Neurol Sci 2007; 24: 270-279.

37. Romeo DM, Sini F, Brogna C, Albamonte E, Ricci D, Mercuri E. Sex differences in cerebral palsy on neuromotor outcome: A critical review. Dev Med Child Neurol 2016; 58: 809-813.

38. Johnston MV, Hagberg H. Sex and the pathogenesis of cerebral palsy. Dev Med Child Neurol 2007; 49: 74-78.

39. Peelen MJ, Kazemier BM, Ravelli AC, et al. Impact of fetal gender on the risk of preterm birth, a national cohort study. Acta Obstet Gynecol Scand 2016; 95: 1034-1041.

40. Himpens E, Van Den Broeck C, Oostra A, Calders P, Vanhaesebrouck P. Prevalence, type, distribution, and severity of cerebral palsy in relation to gestational age: A meta-analytic review. Dev Med Child Neurol 2008; 50: 334-340.

41. Wu YW, Croen LA, Torres AR, Van De Water J, Grether JK, Hsu NN. Interleukin-6 genotype and risk for cerebral palsy in term and near-term infants. Ann Neurol 2009; 66: 663-670.

42. Andersen GL, IrgensLM,Haagaas I, Skranes JS, Meberg AE, Vik T. Cerebral palsy in Norway: Prevalence, subtypes and severity. Eur J Paediatr Neurol 2008; 12: 4-13.

43. Sigurdardóttir S, Thórkelsson T, Halldórsdóttir M, Thorarensen O, Vik T.Trends in prevalence and characteristics of cerebral palsy among Icelandic children born 1990 to 2003. Dev Med Child Neurol 2009; 51: 356-563.

44. Pharoah PO, Cooke T, Johnson MA, King R, Mutch L. Epidemiology of cerebral palsy in England and Scotland, 1984-9. Arch Dis Child Fetal Neonatal Ed 1998; 79: F21-F25.

45. Kuroda MM, Weck ME, Sarwark JF, Hamidullah A, Wainwright MS. Association of apolipoprotein E genotype and cerebral palsy in children. Pediatrics 2007; 119: 306-313.

46. Kulak W, Sobaniec W. Risk factors and prognosis of epilepsy in children with cerebral palsy in north-eastern Poland. Brain Dev 2003; 25: 499-506.

47. Bruck I, Antoniuk SA, Spessatto A, Bem RS, Hausberger R, Pacheco CG. Epilepsy in children with cerebral palsy. Arq Neuropsiquiatr 2001; 59: 35-39.

48. ZafeiriouDI, Kontopoulos EE, Tsikoulas I. Characteristics and prognosis of epilepsy in children with cerebral palsy. J Child Neurol 1999; 14: 289-294.

49. Ukhanova TA, Gorbunov FE, Ivanova VV. Reflexotherapy combined with cortexin in the complex treatment of speech disorders in patients with cerebral palsy. Zh Nevrol Psikhiatr Im SS Korsakova 2011; 111( Pt 1): 19-22.

50. Duman O, İmad FM, Kizilay F, Yucel I, Balkan S, Haspolat S. Serebralpalsili hastaların işlevsel kapasitelerine göre görme sorunlarının değerlendirilmesi. Çocuk Sağlığı ve Hastalıkları Dergisi 2005; 48:130-135.

51. Singhi PD, Ray M, Suri G. Clinical spectrum of cerebral palsy in North India--an analysis of 1,000 cases. J Trop Pediatr 2002; 48: 162-166.

52. Parkes J, White-Koning M, Dickinson HO, et al. Psychological problems in children with cerebral palsy: A cross-sectional European study. J Child Psychol Psychiatry 2008; 49: 405-413.

53. Adın S, Aslan M, Doğan M, Yakıncı C, Alkan A. Term ve preterm serebralpalsili çocuklarda etiyoloji, klinik ve manyetik rezonans görüntüleme bulguları. İnönü Üniversitesi Tıp Fakültesi Dergisi2009; 6: 169-172.

54. Krägeloh-Mann I, Petersen D, Hagberg G, Vollmer B, Hagberg B, Michaelis R. Bilateral spastic cerebral palsy--MRI pathology and origin. Analysis from a representative series of 56 cases. Dev Med Child Neurol 1995; 37: 379-397.

55. Towsley K, Shevell MI, Dagenais L; REPACQ Consortium. Population-based study of neuroimaging findings in children with cerebral palsy. Eur J PaediatrNeurol 2011; 15: 29-35.

56. Braga LW, Borigato EVM, Speck-Martins CE, et al. Apolipoprotein E genotype and cerebral palsy. Dev Med Child Neurol 2010; 52: 666-671.

57. Lawson RD, Badawi N. Etiology of cerebral palsy. Hand Clin 2003; 19: 547-556.

58. Odding E, Roebroeck M, Stam H. The epidemiology of cerebral palsy: Incidence, impairments and risk factors. Disabil Rehabil 2006; 28: 183-191.

59. Harhangi BS, de Rijk MC, van Duijn CM, Van Broeckhoven C, Hofman A, Breteler MM. APOE and the risk of PD with or without dementia in a populationbased study. Neurology 2000; 54: 1272-1276.

60. McMichael GL, Gibson CS, Goldwater PN; South Australian Cerebral Palsy Research Group. Association between Apolipoprotein E genotype and cerebral palsy is not confirmed in a Caucasian population. Hum Genet 2008; 124: 411-416.

61. Kim J, Basak JM, Holtzman DM. The role of apolipoprotein E in Alzheimer’s disease. Neuron 2009; 63: 287-303.

62. Lo TYM, Jones PA, Chambers IR, et al. Modulating effect of apolipoprotein E polymorphisms on secondary brain insult and outcome after childhood brain trauma. Child’s Nerv Syst 2009; 25: 47-54.

63. Lien E, Andersen GL, Bao Y, et al. Gene sequences regulating the production of apoE and cerebral palsy of variable severity. Eur J Paediatr Neurol 2014; 18: 591-596.

64. Lien E, Andersen G, Bao Y, et al. Genes determining the severity of cerebral palsy: the role of single nucleotide polymorphisms on the amount and structure of apolipoprotein E. Acta Paediatr 2015; 104: 701-706.