Epilepsy in patients with Angelman syndrome.
Angelman syndrome (AS) is a neuro-behavioural, genetically determined condition, characterized by ataxic jerky movements, happy sociable disposition and unprovoked bouts of laughter in association with seizures, learning disabilities and language impairment. Most of the cases are hardly diagnosed during infancy as jerky movements, the cardinal sign, appear later in childhood. AS is caused by a variety of genetic mechanisms involving the 15q 11-13 chromosome. About 70% of cases are due to a "de novo" interstitial deletion in the long arm region, arising on the maternally inherited chromosome. The diagnosis is confirmed by methylation test or by mutation analysis of UBE3A gene. The deletion phenotype is generally linked to a more severe clinical picture in that 95% of patients manifest more severe seizures, severe mental and motor retardation, dysmorphic features and microcephaly.The pathogenesis of epilepsy in AS is still not fully understood. The presence in the commonly deleted region of a cluster of genes coding for 3 subunits of the GABAa receptor complex has lead to the hypothesis that GABA neurotransmission is involved. Epilepsy, often severe and hard to control, is present in 85% of patients within the first three years of life, although less than 25% develop seizures during the first year. It was observed that febrile seizures often precede the diagnosis. Most frequent types are atypical absences, generalized tonic-clonic, atonic or myoclonic seizures, with multiple seizure types occurring in 50% of deleted patients. There is still some doubt about the association with West syndrome. The EEG abnormalities are not themselves pathognomonic of AS and both background activity and epileptic discharges vary even in the same patient with time. Nevertheless, the existence of some suggestive patterns should facilitate the early diagnosis allowing the correct genetic counselling for the family. Some drugs seems to act better than others, Valproate, ethosuximide and clonazepam giving the best results.
Fiumara
Agata
A
Pediatric Neurology, Regional Referral Centre for Inborn Errors Metabolism, University of Catania, Italy. agafiu@virgilio.it
Pittalà
Annarita
A
Cocuzza
Mariadonatella
M
Sorge
Giovanni
G
D017204:Angelman Syndrome / Q000150:complications* / Q000235:genetics; D002648:Child; D002869:Chromosome Aberrations; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D018450:Disease Progression; D004827:Epilepsy / Q000209:etiology* / Q000235:genetics; D006801:Humans
Seizure. 2008 Apr;17(3):211-7
17904873
Genet Med. 2009 Nov;11(11):797-805
19938247
J Med Genet. 2001 Dec;38(12):834-45
11748306
Neuropediatrics. 2003 Aug;34(4):169-76
12973656
Epilepsia. 2003 Jun;44(6):873-4; author reply 874
12790908
J Child Neurol. 2009 Aug;24(8):952-8
19666884
Am J Med Genet. 1989 Feb;32(2):285-90
2564739
Am J Med Genet. 1993 Oct 1;47(5):683-6
8266996
Arch Neurol. 2006 Jan;63(1):122-8
16401744
Hum Mol Genet. 2005 Feb 15;14(4):483-92
15615769
Am J Med Genet. 1993 Apr 1;46(1):12-5
7684188
Ann Neurol. 1998 Apr;43(4):485-93
9546330
Dev Med Child Neurol. 2001 Oct;43(10):718-9
11665831
Brain Dev. 2005 Mar;27(2):80-7
15668045
Nat Genet. 1997 Jan;15(1):74-7
8988172
Epilepsia. 2003 Aug;44(8):1051-63
12887436
Neurology. 2000 Mar 14;54(5):1185-8
10720296
Nat Genet. 1997 Sep;17(1):14-5
9288088
Neurology. 2001 Oct 23;57(8):1518-9
11673606
Paediatr Drugs. 2003;5(10):647-61
14510623
Epilepsia. 1997 Feb;38(2):195-9
9048672
Eur J Pediatr. 1988 Jun;147(5):508-13
3409926
Epilepsia. 2009 May;50 Suppl 5:41-4
19469845
Aust Paediatr J. 1978 Sep;14(3):182-4
728011
Nat Genet. 1997 Jan;15(1):70-3
8988171
Epilepsia. 1992 Nov-Dec;33(6):1083-90
1464268
Epilepsia. 2007 Mar;48(3):593-6
17326790
Brain Dev. 1999 Jul;21(5):296-302
10413015
Epilepsia. 2009 Nov;50(11):2331-9
19874386
Epileptic Disord. 2005 Mar;7(1):19-25
15741136
Trends Genet. 1998 May;14(5):194-200
9613204
Am J Med Genet. 1994 Aug 15;52(2):158-63
7802001
Nat Genet. 1995 Apr;9(4):395-400
7795645
J Child Neurol. 1995 Nov;10(6):467-71
8576558
Lancet. 1991 Mar 23;337(8743):694-7
1672177
Arch Dis Child. 1989 Jan;64(1):83-6
2466440