Download PDF
Journal of Pediatric Epilepsy 2015; 04(01): 041-046
DOI: 10.1055/s-0035-1554791
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Wolf–Hirschhorn Syndrome and Epilepsy: An Overview

Ohsuke Migita
1   Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
,
Noriko Udagawa
1   Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
,
Hitoshi Yamamoto
1   Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
› Author Affiliations
Further Information

Publication History

07 September 2014

29 October 2014

Publication Date:
03 July 2015 (online)

    Permissions and Reprints

Abstract

The Wolf–Hirschhorn syndrome (WHS, OMIM194190) is a contiguous gene deletion syndrome of the distal part of the short arm of chromosome 4 (4p16 region) characterized by a distinctive facial appearance, intrauterine and postnatal growth delay, intellectual disability, and seizures. The WHS clinical spectrum is complex and variable. Typically, more than 90% of WHS-related patients begin seizures in the first 3 years of life. In these cases, most of the epilepsy is well controlled, and over half of the patients stopped having seizures after adolescence. Etiology and/or genetics of their seizures were unclear. The clinical data on the association between epilepsy and chromosomal abnormalities is likely to improve our understanding of the functions and mechanisms of genes related to epilepsy. Future studies would be needed for a deeper understanding of WHS.

Keywords

Wolf–Hirschhorn syndrome - 4p deletion - epilepsy - seizure
 

  • References

  • 1 Cooper HL, Hirschhorn K. Apparent deletion of short arms of one chromosome (4 or 5) in a child with defects of midline fusion. Human Chromosome Newslett 1961; 4: 14
    PubMedGoogle Scholar
  • 2 Hirschhorn K, Cooper HL, Firschein IL. Deletion of short arms of chromosome 4-5 in a child with defects of midline fusion. Humangenetik 1965; 1 (5) 479-482
    PubMedGoogle Scholar
  • 3 Wolf U, Reinwein H, Porsch R, Schröter R, Baitsch H. Deficiency on the short arms of a chromosome No. 4 [in German]. Humangenetik 1965; 1 (5) 397-413
    PubMedGoogle Scholar
  • 4 Wolf U, Porsch R, Baitsch H, Reinwein H. Deletion on short arms of a B-Chromosome without ‘’CRI DU CHAT'' syndrome. Lancet 1965; 1 (7388) 769
    PubMedGoogle Scholar
  • 5 Lurie IW, Lazjuk GI, Ussova YI, Presman EB, Gurevich DB. The Wolf-Hirschhorn syndrome. I. Genetics. Clin Genet 1980; 17 (6) 375-384
    PubMedGoogle Scholar
  • 6 Battaglia A, Filippi T, Carey JC. Update on the clinical features and natural history of Wolf-Hirschhorn (4p-) syndrome: experience with 87 patients and recommendations for routine health supervision. Am J Med Genet C Semin Med Genet 2008; 148C (4) 246-251
    CrossrefPubMedGoogle Scholar
  • 7 Schinzel A, Niedrist D. Chromosome imbalances associated with epilepsy. Am J Med Genet 2001; 106 (2) 119-124
    CrossrefPubMedGoogle Scholar
  • 8 Hirschhorn K. A short history of the initial discovery of the Wolf-Hirschhorn syndrome. Am J Med Genet C Semin Med Genet 2008; 148C (4) 244-245
    CrossrefPubMedGoogle Scholar
  • 9 Battaglia A, Carey JC, Cederholm P, Viskochil DH, Brothman AR, Galasso C. Natural history of Wolf-Hirschhorn syndrome: experience with 15 cases. Pediatrics 1999; 103 (4, Pt 1) 830-836
    CrossrefPubMedGoogle Scholar
  • 10 Zollino M, Murdolo M, Marangi G , et al. On the nosology and pathogenesis of Wolf-Hirschhorn syndrome: genotype-phenotype correlation analysis of 80 patients and literature review. Am J Med Genet C Semin Med Genet 2008; 148C (4) 257-269
    CrossrefPubMedGoogle Scholar
  • 11 Battaglia A, Carey JC. Seizure and EEG patterns in Wolf-Hirschhorn (4p-) syndrome. Brain Dev 2005; 27 (5) 362-364
    CrossrefPubMedGoogle Scholar
  • 12 Zankl A, Addor MC, Maeder-Ingvar MM, Schorderet DF. A characteristic EEG pattern in 4p-syndrome: case report and review of the literature. Eur J Pediatr 2001; 160 (2) 123-127
    CrossrefPubMedGoogle Scholar
  • 13 Sgrò V, Riva E, Canevini MP , et al. 4p(-) syndrome: a chromosomal disorder associated with a particular EEG pattern. Epilepsia 1995; 36 (12) 1206-1214
    CrossrefPubMedGoogle Scholar
  • 14 Battaglia A, Filippi T, South ST, Carey JC. Spectrum of epilepsy and electroencephalogram patterns in Wolf-Hirschhorn syndrome: experience with 87 patients. Dev Med Child Neurol 2009; 51 (5) 373-380
    CrossrefPubMedGoogle Scholar
  • 15 Guerrini R, Gobbi G, Genton P, Bonanni P, Carrozzo R. Chromosomal abnormalities. In: Engel Jr J, Pedley TA, , eds. Epilepsy: A Comprehensive Textbook. Philadelphia, PA: Lippincott-Raven; 1997: 2533-2546
    Google Scholar
  • 16 Battaglia D, Zampino G, Zollino M , et al. Electroclinical patterns and evolution of epilepsy in the 4p- syndrome. Epilepsia 2003; 44 (9) 1183-1190
    CrossrefPubMedGoogle Scholar
  • 17 Righini A, Ciosci R, Selicorni A , et al. Brain magnetic resonance imaging in Wolf-Hirschhorn syndrome. Neuropediatrics 2007; 38 (1) 25-28
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Verbrugge J, Choudhary AK, Ladda R. Tethered cord, corpus callosum abnormalities, and periventricular cysts in Wolf-Hirschhorn syndrome. Report of two cases and review of the literature. Am J Med Genet A 2009; 149A (10) 2280-2284
    CrossrefPubMedGoogle Scholar
  • 19 Lazjuk GI, Lurie IW, Ostrowskaja TI , et al. The Wolf-Hirschhorn syndrome. II. Pathologic anatomy. Clin Genet 1980; 18 (1) 6-12
    PubMedGoogle Scholar
  • 20 Gottfried M, Lavine L, Roessmann U. Neuropathological findings in Wolf-Hirschhorn (4p-) syndrome. Acta Neuropathol 1981; 55 (2) 163-165
    CrossrefPubMedGoogle Scholar
  • 21 South ST, Whitby H, Battaglia A, Carey JC, Brothman AR. Comprehensive analysis of Wolf-Hirschhorn syndrome using array CGH indicates a high prevalence of translocations. Eur J Hum Genet 2008; 16 (1) 45-52
    CrossrefPubMedGoogle Scholar
  • 22 Buckton KE, O'Riordan ML, Ratcliffe S , et al. A G-band study of chromosomes in liveborn infants. Ann Hum Genet 1980; 43 (3) 227-239
    CrossrefPubMedGoogle Scholar
  • 23 Mulley JC, Mefford HC. Epilepsy and the new cytogenetics. Epilepsia 2011; 52 (3) 423-432
    CrossrefPubMedGoogle Scholar
  • 24 Yamanouchi H, Imataka G, Nakagawa E , et al. An analysis of epilepsy with chromosomal abnormalities. Brain Dev 2005; 27 (5) 370-377
    CrossrefPubMedGoogle Scholar
  • 25 Maas NM, Van Buggenhout G, Hannes F , et al. Genotype-phenotype correlation in 21 patients with Wolf-Hirschhorn syndrome using high resolution array comparative genome hybridisation (CGH). J Med Genet 2008; 45 (2) 71-80
    PubMedGoogle Scholar
  • 26 Engbers H, van der Smagt JJ, van 't Slot R, Vermeesch JR, Hochstenbach R, Poot M. Wolf-Hirschhorn syndrome facial dysmorphic features in a patient with a terminal 4p16.3 deletion telomeric to the WHSCR and WHSCR 2 regions. Eur J Hum Genet 2009; 17 (1) 129-132
    CrossrefPubMedGoogle Scholar
  • 27 Misceo D, Barøy T, Helle JR, Braaten O, Fannemel M, Frengen E. 1.5Mb deletion of chromosome 4p16.3 associated with postnatal growth delay, psychomotor impairment, epilepsy, impulsive behavior and asynchronous skeletal development. Gene 2012; 507 (1) 85-91
    CrossrefPubMedGoogle Scholar
  • 28 Shimizu K, Wakui K, Kosho T , et al. Microarray and FISH-based genotype-phenotype analysis of 22 Japanese patients with Wolf-Hirschhorn syndrome. Am J Med Genet A 2014; 164A (3) 597-609
    PubMedGoogle Scholar
  • 29 Zollino M, Orteschi D, Ruiter M , et al. Unusual 4p16.3 deletions suggest an additional chromosome region for the Wolf-Hirschhorn syndrome-associated seizures disorder. Epilepsia 2014; 55 (6) 849-857
    CrossrefPubMedGoogle Scholar
  • 30 Wright TJ, Ricke DO, Denison K , et al. A transcript map of the newly defined 165.  kb Wolf-Hirschhorn syndrome critical region. Hum Mol Genet 1997; 6 (2) 317-324
    CrossrefPubMedGoogle Scholar
  • 31 Zollino M, Lecce R, Fischetto R , et al. Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining a new critical region, WHSCR-2. Am J Hum Genet 2003; 72 (3) 590-597
    CrossrefPubMedGoogle Scholar
  • 32 Rodríguez L, Zollino M, Climent S , et al. The new Wolf-Hirschhorn syndrome critical region (WHSCR-2): a description of a second case. Am J Med Genet A 2005; 136 (2) 175-178
    PubMedGoogle Scholar
  • 33 Hajdu I, Ciccia A, Lewis SM, Elledge SJ. Wolf-Hirschhorn syndrome candidate 1 is involved in the cellular response to DNA damage. Proc Natl Acad Sci U S A 2011; 108 (32) 13130-13134
    CrossrefPubMedGoogle Scholar
  • 34 Paradowska-Stolarz AM. Wolf-Hirschhorn syndrome (WHS) - literature review on the features of the syndrome. Adv Clin Exp Med 2014; 23 (3) 485-489
    CrossrefPubMedGoogle Scholar
  • 35 Okamoto N, Ohmachi K, Shimada S, Shimojima K, Yamamoto T. 109 kb deletion of chromosome 4p16.3 in a patient with mild phenotype of Wolf-Hirschhorn syndrome. Am J Med Genet A 2013; 161A (6) 1465-1469
    PubMedGoogle Scholar
  • 36 Hannes F, Hammond P, Quarrell O, Fryns JP, Devriendt K, Vermeesch JR. A microdeletion proximal of the critical deletion region is associated with mild Wolf-Hirschhorn syndrome. Am J Med Genet A 2012; 158A (5) 996-1004
    CrossrefPubMedGoogle Scholar
  • 37 Fisch GS, Battaglia A, Parrini B, Youngblom J, Simensen R. Cognitive-behavioral features of children with Wolf-Hirschhorn syndrome: preliminary report of 12 cases. Am J Med Genet C Semin Med Genet 2008; 148C (4) 252-256
    CrossrefPubMedGoogle Scholar