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Long-term outcome of epilepsy in patients with Prader–Willi syndrome

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An Erratum to this article was published on 27 November 2014

Abstract

Prader–Willi syndrome is a multisystemic genetic disorder that can be associated with epilepsy. There is insufficient information concerning the clinical and electroencephalographic characteristics of epilepsy and the long-term outcome of these patients. The aim of this study is to describe seizure types, electroencephalographic patterns and long-term seizure outcome in Prader–Willi syndrome patients suffering from epilepsy. We retrospectively studied 38 patients with Prader–Willi syndrome and seizures. Results of neuroimaging studies were obtained for 35 individuals. We subdivided these patients into two groups: group A, 24 patients, without brain lesions; and group B, 11 patients, with brain abnormalities. All patients were re-evaluated after a period of at least 10 years. Twenty-one patients (55.2 %) were affected by generalized epilepsy and 17 patients (44.8 %) presented focal epilepsy. The most common seizure type was generalized tonic–clonic seizure. The mean age at seizure onset was 4.5 years (ranged from 1 month to 14 years). In the follow-up period, seizure freedom was achieved in 32 patients (84.2 %). Seizure freedom was associated with electroencephalographic normalization, while the six children presenting drug-resistant epilepsy showed persistence of electroencephalographic abnormalities. Group B patients showed a higher prevalence of drug-resistant epilepsy. Patients with Prader–Willi syndrome were frequently affected by generalized seizures. Most of the patients had a favorable evolution, although, patients with brain abnormalities presented a worse outcome, suggesting that the presence of these lesions can influence the response to antiepileptic therapy.

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References

  1. Whittington JE, Holland AJ, Webb T, Butler J, Clarke D, Boer H (2001) Population prevalence and estimated birth incidence and mortality rate for people with Prader-Willi syndrome in one UK Health Region. J Med Genet 38:792–798

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Prader A, Labhart A, Willi H (1956) Ein Syndrom von Adipositas, Kleinwuchs, Kryptorchismus und Oligophrenie nach myatonieartigem Zustand im Neugeborenenalter. Schweiz Med Wochenschr 86:1260–1261

    Google Scholar 

  3. Holm VA, Cassidy SB, Butler MG, Hanchett JM, Greenswag LR, Whitman BY, Greenberg F (1993) Prader-Willi syndrome: consensus diagnostic criteria. Pediatrics 91:398–402

    CAS  PubMed  Google Scholar 

  4. Gunay-Augun M, Schwartz S, Heeger S, O’Riordan M, Cassidy SB (2001) The changing purpose of Prader-Willi syndrome clinical diagnostic criteria. Pediatrics 108:E92

    Article  Google Scholar 

  5. Kuwano A, Mutirangura A, Dittrich B, Buiting K, Horsthemke B, Saitoh S, Niikawa N et al (1992) Molecular dissection of the Prader-Willi/Angelman syndrome region (15qll-13) by YAC cloning and FISH analysis. Hum Mol Genet 1:417–425

    Article  CAS  PubMed  Google Scholar 

  6. Benson LA, Maski KP, Kothare SV, Bourgeois BF (2010) New onset epilepsy in Prader-Willi syndrome: semiology and literature review. Pediatr Neurol 43:297–299

    Article  PubMed  Google Scholar 

  7. Helbing-Zwanenburg B, Kamphuisen HA, Mourtazaev MS (1993) The origin of excessive daytime sleepiness in the Prader-Willi syndrome. J Intellect Disabil Res 37:533–541

    Article  PubMed  Google Scholar 

  8. Tobias ES, Tolmie JL, Stephenson JB (2002) Cataplexy in the Prader-Willy syndrome. Arch Dis Child 87:170

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Wang PJ, Hou JW, Sue WC, Lee WT (2005) Electroclinical characteristics of seizures-comparing Prader-Willi syndrome with Angelman syndrome. Brain Dev 27:101–107

    Article  PubMed  Google Scholar 

  10. Kumada T, Ito M, Miyajima T et al (2005) Multi-institutional study on the correlations between chromosomal abnormalities and epilepsy. Brain Dev 27:127–134

    Article  PubMed  Google Scholar 

  11. Fan Z, Greenwood R, Fisher A, Pendyal S, Powell CM (2009) Characteristics and frequency of seizure disorder in 56 patients with Prader-Willi syndrome. Am J Med Genet Part A 149A:1581–1584

    Article  PubMed  Google Scholar 

  12. Varela MC, Kok F, Setian N, Kim CA, Koiffman CP (2005) Impact of molecular mechanism including deletion size, on Prader-Willi syndrome phenotype: a study of 75 patients. Clin Genet 67:47–52

    Article  CAS  PubMed  Google Scholar 

  13. Vendrame M, Maski KP, Chatterjee M, Heshmati A, Krishnamoorthy K, Tan WH, Kothare SV (2010) Epilepsy in Prader-Willi syndrome: clinical characteristics and correlation to genotype. Epil Behav 19:306–310

    Article  Google Scholar 

  14. Sinnema M, Maaskant MA, Lantman-de Valk HMJ, van Nieuwpoort IC, Drent ML, Curfs LMG, Schrander-Stumpel CTRM (2011) Physical health problems in adults with Prader-Willi syndrome. Am J Med Genet Part A 155:2112–2124

    Article  Google Scholar 

  15. Takeshita E, Murakami N, Sakuta R, Nagai T (2013) Evaluating the frequency and characteristics of seizures in 142 Japanese patients with Prader-Willi syndrome. Am J Med Genet Part A 161A:2052–2055

    Article  PubMed  Google Scholar 

  16. Gilboa T, Gross-Tsur V (2013) Epilepsy in Prader-Willi syndrome: experience of a national referral centre. Dev Med Child Neurol 55:857–861

    Article  PubMed  Google Scholar 

  17. Iughetti L, Bosio L, Corrias A et al (2008) Pituitary height and neuroradiological alterations in patients with Prader-Labhart-Willi syndrome. Eur J Pediatr 167:701–702

    Article  CAS  PubMed  Google Scholar 

  18. Miller JL, Couch JA, Schmalfuss I, He G, Liu Y, Driscoll DJ (2007) Intracranial abnormalities detected by three-dimensional magnetic resonance imaging in Prader-Willi syndrome. Am J Med Genet A 143:476–483

    Article  Google Scholar 

  19. American Society of Human Genetics/American College of Medical Genetics (1996) Diagnostic testing for Prader-Willi and Angelman syndromes: report of the ASHG/ACMG test and technology transfer committee. Am J Hum Genet 58:1085–1088

    Google Scholar 

  20. Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, Engel J Jr, Forsgren L, French JA, Glynn M, Hesdorffer DC, Lee BI, Mathern GW, Mosh SL, Perucca E, Scheffer IE, Tomson T, Watanabe M, Wiebe S (2014) Ilae official report: a practical clinical definition of epilepsy. Epilepsia 55(4):475–482

    Article  PubMed  Google Scholar 

  21. Butler JV, Whittington JE, Holland AJ, Boer H, Clarke D, Webb T (2002) Prevalence of, and risk factors for, physical ill-health in people with Prader-Willi syndrome: a population-based study. Dev Med Child Neurol 44:248–255

    Article  CAS  PubMed  Google Scholar 

  22. Laan LA, Renier WO, Arts WF, Buntinx IM, vd Burgt IJ, Stroink H et al (1997) Evolution of epilepsy and EEG findings in Angelman syndrome. Epilepsia 38:195–199

    Article  CAS  PubMed  Google Scholar 

  23. Stafstrom CE, Paxtot OF, Gilmore HE, Wisniewski KE (1991) Seizures in children with Down syndrome: etiology, characteristics and outcome. Dev Med Child Neurol 33:191–200

    Article  CAS  PubMed  Google Scholar 

  24. Belcastro V, D’Egidio C, Striano P, Verrotti A (2013) Metabolic and endocrine effects of valproic acid chronic treatment. Epilepsy Res 107:1–8

    Article  CAS  PubMed  Google Scholar 

Download references

Conflicts of interest

All the authors have declared no conflicts of interests.

Ethical standard

Written informed consent was obtained by parents or caregivers of all recruited patients. This study was approved by the Ethical Committee at the University Hospital “Santa Maria della Misericordia” in Perugia, Italy.

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Authors and Affiliations

  1. Department of Pediatrics, University of Perugia, Perugia, Italy

    Alberto Verrotti & Daniela Laino

  2. Neurology Unit, “Bambino Gesù” Children’s Hospital, IRCCS, Rome, Italy

    Raffaella Cusmai

  3. Pediatric Acute and Emergency Operative Unit and Department, Policlinico-Vittorio Emanuele University Hospital, University of Catania, Catania, Italy

    Raffaele Falsaperla

  4. Unit of Child Neuropsychiatry, Department of Basic Medical Sciences, Neuroscience and Sense Organs, “Aldo Moro” University of Bari, Bari, Italy

    Lucia Margari & Francesca Operto

  5. Section of Child Neuropsychiatry, Department of Pediatrics, University of Catania, Catania, Italy

    Renata Rizzo

  6. Department of Pediatrics, Pavia University Foundation, IRCCS Policlinico San Matteo, Pavia, Italy

    Salvatore Savasta

  7. Pediatric Neurology-Immunology and Endocrinology Unit, University of Siena, Siena, Italy

    Salvatore Grosso

  8. Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Institute “Gaslini”, University of Genova, Genoa, Italy

    Pasquale Striano

  9. Neurology Unit, Department of Neuroscience, “Sant’Anna” Hospital, Como, Italy

    Vincenzo Belcastro

  10. Neuropsychiatry Unit, Department of Pediatrics, University of Bologna, Bologna, Italy

    Emilio Franzoni

  11. Child Neurology and Psychiatry Unit, Department of Systems Medicine, Tor Vergata University Hospital of Rome, Rome, Italy

    Paolo Curatolo

  12. Pediatric Neuropsychiatric Division, “Ospedali Civili”, Brescia, Italy

    Lucio Giordano

  13. Department of Pediatric Neuroscience, Foundation I.R.C.C.S. Neurological Institute C. Besta, Milan, Italy

    Elena Freri

  14. Department of Pediatrics, University of Chieti, Chieti, Italy

    Sara Matricardi & Francesco Chiarelli

  15. Division of Child Neurology, Department of Pediatrics, University “La Sapienza” Rome, Rome, Italy

    Dario Pruna

  16. Pediatric Neurology Unit, Department of Women’s and Children’s Health, University of Padova, Padua, Italy

    Irene Toldo

  17. Department of Pediatrics, University of L’Aquila, L’Aquila, Italy

    Elisabetta Tozzi

  18. Section of Ophthalmology, Department of Experimental and Clinical Sciences, University of Chieti, Chieti, Italy

    Lucio Lobefalo

  19. Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy

    Emma Altobelli

  20. Chair of Pediatrics, Child Neurology, II Faculty of Medicine, University of Rome, Rome, Italy

    Alberto Spalice

Authors
  1. Alberto Verrotti
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  2. Raffaella Cusmai
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  3. Daniela Laino
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  4. Raffaele Falsaperla
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  5. Lucia Margari
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  6. Renata Rizzo
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  7. Salvatore Savasta
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  8. Salvatore Grosso
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  9. Pasquale Striano
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  10. Vincenzo Belcastro
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  11. Emilio Franzoni
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  12. Paolo Curatolo
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  13. Lucio Giordano
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  14. Elena Freri
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  15. Sara Matricardi
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  16. Dario Pruna
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  17. Irene Toldo
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  18. Elisabetta Tozzi
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  19. Lucio Lobefalo
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  20. Francesca Operto
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  21. Emma Altobelli
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  22. Francesco Chiarelli
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  23. Alberto Spalice
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Corresponding author

Correspondence to Alberto Verrotti.

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Verrotti, A., Cusmai, R., Laino, D. et al. Long-term outcome of epilepsy in patients with Prader–Willi syndrome. J Neurol 262, 116–123 (2015). https://doi.org/10.1007/s00415-014-7542-1

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  • DOI: https://doi.org/10.1007/s00415-014-7542-1

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