Original article| Volume 27, ISSUE 5, P378-382, August 2005

Epilepsy and neurological findings in 11 individuals with 1p36 deletion syndrome


      The 1p36 deletion syndrome is a newly delineated multiple congenital anomalies/mental retardation syndrome characterized by mental retardation, growth delay, epilepsy, congenital heart defects, characteristic facial appearance, and precocious puberty. We analyzed 11 patients by fluorescence in situ hybridization (FISH) using commercially available bacterial artificial chromosome and P1-derived artificial chromosome genomic clones to define the chromosomal deletion responsible for the 1p36 deletion syndrome. Cytogenetic investigation revealed two cases with a terminal deletion of 1p36. Nine patients had an apparently normal karyotype with standard G-bands by trypsin using Giemsa (GTG), but FISH screening with the highly polymorphic genetic marker D1Z2, which is mapped to 1p36.3 and contains an unusual reiterated 40-bp variable number tandem repeat, revealed a submicroscopic deletion. All patients had severe to profound mental retardation. Based on the University of California Santa Cruz Genome Browser, we constructed a deletion map and analyzed the relationship between neurological findings and chromosomal deletions for the 11 cases. Six cases had intractable epilepsy and three had no seizures. The common deletion interval was about 1 million base pairs (Mbp) located between RP11-82D16 and RP4-785P20 (Rho guanine exchange factor (GEF) 16). The severity of clinical symptoms correlates with the size of the deletion. This is demonstrated by the 3 patients with at least 8 Mbp deletions that display profound mental retardation and congenital heart defects. Although haploinsufficiency of the potassium channel beta-subunit (KCNAB2) is thought to be responsible for intractable seizures in the 1p36 deletion syndrome, this was not the case for 3 of the 11 patients in this study. Further investigation of the 1p36 region is necessary to allow identification of genes responsible for the 1p36 deletion syndrome.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Brain and Development
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Battaglia A.
        • Carey J.C.
        Diagnostic evaluation of developmental delay/mental retardation: an overview.
        Am J Med Genet. 2003; 117C: 3-14
        • Flint J.
        • Wilkie A.O.M.
        • Buckle V.J.
        • Winter R.M.
        • Holland A.J.
        • McDermid H.E.
        The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation.
        Nat Genet. 1995; 9: 132-139
        • Knight S.J.L.
        • Flint J.
        Perfect endings: a review of subtelomeric probes and their use in clinical diagnosis.
        J Med Genet. 2000; 37: 401-409
        • Knight S.J.L.
        • Regan R.
        • Nicord A.
        • Horsley S.W.
        • Kearney L.
        • Homfray T.
        • et al.
        Subtle chromosomal rearrangements in children with unexplained mental retardation.
        Lancet. 1999; 354: 1676-1681
        • Baker E.
        • Hinton L.
        • Callen D.F.
        • Altree M.
        • Dobbie A.
        • Eyre H.J.
        • et al.
        Study of 250 children with idiopathic mental retardation reveals nine cryptic and diverse subtelomeric chromosome anomalies.
        Am J Med Genet. 2002; 107: 285-293
        • Shapira S.K.
        • McCaskill C.
        • Northrup H.
        • Spikes A.S.
        • Elder F.F.
        • Sutton V.R.
        • et al.
        Chromosome 1p36 deletions: the clinical phenotype and molecular characterization of a common newly delineated syndrome.
        Am J Hum Genet. 1997; 61: 642-650
        • Wu Y.Q.
        • Heilstedt H.A.
        • Bedell J.A.
        • May K.M.
        • Starkey D.E.
        • McPherson J.D.
        • et al.
        Molecular refinement of the 1p36 deletion syndrome reveals size diversity and a preponderance of maternally derived deletions.
        Hum Mol Genet. 1999; 8: 313-321
        • Slavotinek A.
        • Shaffer L.G.
        • Shapira S.K.
        Monosomy 1p36.
        J Med Genet. 1999; 36: 657-663
        • Riegel M.
        • Castellan C.
        • Balmer D.
        • Brecevic L.
        • Schinzel A.
        Terminal deletion, del(1)(p36.3), detected through screening for terminal deletions in patients with unclassified malformation syndromes.
        Am J Med Genet. 1999; 82: 249-253
        • De Vries B.B.
        • White S.M.
        • Knight S.J.L.
        • Regan R.
        • Homfray T.
        • Young I.D.
        • et al.
        Clinical studies on submicroscopic subtelomeric rearrangements: a checklist.
        J Med Genet. 2001; 38: 145-150
        • Masuno M.
        • Imaizumi K.
        • Kurosawa K.
        • Makita Y.
        • Petrij F.
        • Dauwerse H.G.
        • et al.
        Submicroscopic deletion of chromosome region 16p13.3 in a Japanese patient with Rubinstein-Taybi syndrome.
        Am J Med Genet. 1994; 53: 352-354
      1. The URL for data presented is as follows:

        • Okamoto N.
        • Toribe Y.
        • Nakajima T.
        • Okinaga T.
        • Kurosawa K.
        • Nonaka I.
        • et al.
        A girl with 1p36 deletion syndrome and congenital fiber type disproportion myopathy.
        J Hum Genet. 2002; 47: 556-559
        • Heilstedt H.A.
        • Burgess D.L.
        • Anderson A.E.
        • Chedrawi A.
        • Tharp B.
        • Lee O.
        • et al.
        Loss of the potassium channel β-subunit gene, KCNAB2, is associated with epilepsy in patients with 1p36 deletion syndrome.
        Epilepsia. 2001; 42: 1103-1111
        • Hirose S.
        • Okada M.
        • Yamakawa K.
        • Sugawara T.
        • Fukuma G.
        • Ito M.
        • et al.
        Genetic abnormalities underlying familial epilepsy syndromes.
        Brain Dev. 2001; 24: 211-222
        • Heilstedt H.A.
        • Ballif B.C.
        • Howard L.A.
        • Lewis R.A.
        • Stal S.
        • Kashork C.D.
        • et al.
        Physical map of 1p36, placement of breakpoints in monosomy 1p36, and clinical characterization of the syndrome.
        Am J Hum Genet. 2003; 72: 1200-1212