Electroencephalographic findings in ATRX syndrome: A new case series and review of literature

Published:August 17, 2022DOI:


      • Epilepsy occurs in about 30% of patients with ATRX syndrome.
      • Generalized seizures including clonic, tonic, myoclonic or myoclonic absences are frequently described in this syndrome.
      • We report on seven unpublished Italian patients with ATRX syndrome, focusing on epilepsy and EEG pattern.
      • We described a typical EEG pattern characterized by diffuse background slowing with superimposed low voltage fast activity.


      Alpha-thalassemia X-linked intellectual disability syndrome (ATRX) is a rare genetic condition caused by mutations in the ATRX gene characterized by distinctive dysmorphic features, alpha thalassemia, mild-to-profound intellectual disability, and epilepsy, reported in nearly 30% of the patients. To date, different types of seizures are reported in patients with ATRX syndrome including either clonic, tonic, myoclonic seizures or myoclonic absences. However, an accurate analysis of electroencephalographic features is lacking in literature. We report on the epileptic and electroencephalographic phenotype of seven unpublished patients with ATRX syndrome, highlighting the presence of a peculiar EEG pattern characterized by diffuse background slowing with superimposed low voltage fast activity. Likewise, we also review the available literature on this topic.


      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 European Journal of Paediatric Neurology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • León N.Y.
        • Harley V.R.
        ATR-X syndrome: genetics, clinical spectrum, and management.
        Hum. Genet. 2021 Dec; 140: 1625-1634
        • Lee H.
        • Deignan J.L.
        • Dorrani N.
        • Strom S.P.
        • Kantarci S.
        • Quintero-Rivera F.
        • Das K.
        • Toy T.
        • Harry B.
        • Yourshaw M.
        • Fox M.
        • Fogel B.L.
        • Martinez-Agosto J.A.
        • Wong D.A.
        • Chang V.Y.
        • Shieh P.B.
        • Palmer C.G.
        • Dipple K.M.
        • Grody W.W.
        • Vilain E.
        • Nelson S.F.
        Clinical exome sequencing for genetic identification of rare Mendelian disorders.
        JAMA. 2014 Nov 12; 312: 1880-1887
        • Richards S.
        • Aziz N.
        • Bale S.
        • Bick D.
        • Das S.
        • Gastier-Foster J.
        • Grody W.W.
        • Hegde M.
        • Lyon E.
        • Spector E.
        • Voelkerding K.
        • Rehm H.L.
        • ACMG Laboratory Quality Assurance Committee
        Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology.
        Genet. Med. 2015 May; 17: 405-424
        • Moncini S.
        • Bedeschi M.F.
        • Castronovo P.
        • Crippa M.
        • Calvello M.
        • Garghentino R.R.
        • Scuvera G.
        • Finelli P.
        • Venturin M.
        ATRX mutation in two adult brothers with non-specific moderate intellectual disability identified by exome sequencing.
        Meta Gene. 2013 Oct 29; 1: 102-108
        • Basehore M.J.
        • Michaelson-Cohen R.
        • Levy-Lahad E.
        • Sismani C.
        • Bird L.M.
        • Friez M.J.
        • Walsh T.
        • Abidi F.
        • Holloway L.
        • Skinner C.
        • McGee S.
        • Alexandrou A.
        • Syrrou M.
        • Patsalis P.C.
        • Raymond G.
        • Wang T.
        • Schwartz C.E.
        • King M.C.
        • Stevenson R.E.
        Alpha-thalassemia intellectual disability: variable phenotypic expression among males with a recurrent nonsense mutation - c.109C>T (p.R37X).
        Clin. Genet. 2015 May; 87: 461-466
        • Guerrini R.
        • Shanahan J.L.
        • Carrozzo R.
        • Bonanni P.
        • Higgs D.R.
        • Gibbons R.J.
        A nonsense mutation of the ATRX gene causing mild mental retardation and epilepsy.
        Ann. Neurol. 2000 Jan; 47: 117-121
        • Giacomini T.
        • Vari M.S.
        • Janis S.
        • Prato G.
        • Pisciotta L.
        • Rocchi A.
        • Michelucci A.
        • Di Rocco M.
        • Gandullia P.
        • Mattioli G.
        • Sacco O.
        • Morana G.
        • Mancardi M.M.
        Epileptic encephalopathy, myoclonus-dystonia, and premature pubarche in siblings with a novel C-terminal truncating mutation in ATRX gene.
        Neuropediatrics. 2019 Oct; 50: 327-331
        • Thienpont B.
        • de Ravel T.
        • Van Esch H.
        • Van Schoubroeck D.
        • Moerman P.
        • Vermeesch J.R.
        • Fryns J.P.
        • Froyen G.
        • Lacoste C.
        • Badens C.
        • Devriendt K.
        Partial duplications of the ATRX gene cause the ATR-X syndrome.
        Eur. J. Hum. Genet. 2007 Oct; 15: 1094-1097
        • Yun K.W.
        • Chae S.A.
        • Lee J.J.
        • Yun S.W.
        • Yoo B.H.
        • Lim I.S.
        • Choi E.S.
        • Lee M.K.
        The first case of X-linked Alpha-thalassemia/mental retardation (ATR-X) syndrome in Korea.
        J. Kor. Med. Sci. 2011 Jan; 26: 146-149