Epileptic Encephalopathy, Myoclonus–Dystonia, and Premature Pubarche in Siblings with a Novel C-Terminal Truncating Mutation in ATRX Gene

Thea Giacomini; Maria Stella Vari; Sara Janis; Giulia Prato; Livia Pisciotta; Alessia Rocchi; Angela Michelucci; Maja Di Rocco; Paolo Gandullia; Girolamo Mattioli; Oliviero Sacco; Giovanni Morana; Maria Margherita Mancardi

doi:10.1055/s-0039-1692141

Neuropediatrics, Table of Contents

Neuropediatrics 2019; 50(05): 327-331
DOI: 10.1055/s-0039-1692141

Short Communication

Georg Thieme Verlag KG Stuttgart · New York

Epileptic Encephalopathy, Myoclonus–Dystonia, and Premature Pubarche in Siblings with a Novel C-Terminal Truncating Mutation in ATRX Gene

Thea Giacomini

¹Unit of Child Neuropsychiatry, Istituto Giannina Gaslini, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Children's Sciences, University of Genova, Genova, Italy

,

Maria Stella Vari

²Unit of Neurology and Neuromuscolar Diseases, Department of Clinical and Surgical Neurosciences and Rehabilitation, Istituto Giannina Gaslini, Genova, Italy

,

Sara Janis

¹Unit of Child Neuropsychiatry, Istituto Giannina Gaslini, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Children's Sciences, University of Genova, Genova, Italy

,

Giulia Prato

³Unit of Child Neuropsychiatry, Epilepsy Centre, Department of Clinical and Surgical Neurosciences and Rehabilitation, IRCSS Istituto Giannina Gaslini, Genova, Italy

,

Livia Pisciotta

¹Unit of Child Neuropsychiatry, Istituto Giannina Gaslini, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Children's Sciences, University of Genova, Genova, Italy

,

Alessia Rocchi

⁴Unit of First Aid, Newborn and Children Area, Department of Woman, Child and Newborn, IRCCS Ca' Granda Maggiore Policlinico Hospital, Milan, Italy

,

Angela Michelucci

⁵Laboratory of Medical Genetic Unit, Azienda Ospedaliero Universitaria Pisana, S. Chiara Hospital, Pisa, Italy

,

Maja Di Rocco

⁶Unit of Rare Diseases, Department of Pediatrics, IRCSS Istituto Giannina Gaslini, Genova, Italy

,

Paolo Gandullia

⁷Unit of Gastroenterology, IRCSS Istituto Giannina Gaslini, Genova, Italy

,

Girolamo Mattioli

⁸Unit of Surgery, IRCSS Istituto Giannina Gaslini, Genova, Italy

,

Oliviero Sacco

⁹Unit of Pneumology, IRCSS Istituto Giannina Gaslini, Genova, Italy

,

Giovanni Morana

¹⁰Unit of Neuroradiology, IRCSS Istituto Giannina Gaslini, Genova, Italy

,

Maria Margherita Mancardi

³Unit of Child Neuropsychiatry, Epilepsy Centre, Department of Clinical and Surgical Neurosciences and Rehabilitation, IRCSS Istituto Giannina Gaslini, Genova, Italy

› Author Affiliations

Abstract

The X-linked alpha thalassemia mental retardation (ATR-X) syndrome is a genetic disorder caused by X-linked recessive mutations in ATRX gene, related to a wide spectrum of clinical manifestations, such as alpha thalassemia, developmental delay, genital abnormalities, and gastrointestinal disorders. Patients with ATR-X syndrome can suffer from different types of epileptic seizures, but a severe epileptic encephalopathy pattern has not been described to date. We describe, for the first time, two brothers with genetically confirmed ATR-X syndrome who presented with drug-resistant epileptic encephalopathy, with tonic and polimorphic seizures reported in the elder brother and epileptic spasms in the younger brother. Moreover, both brothers showed a peculiar movement disorder with myoclonus–dystonia, worsened during periods of distress or pain. These cases expand the clinical spectrum of ATR-X syndrome and open new opportunities for the molecular diagnosis of ATRX mutations in male patients with severe epileptic encephalopathies and movement disorders.

Keywords

ATR-X syndrome - epileptic encephalopathy - myoclonus-dystonia - premature pubarche

Full Text

References

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Supplementary Material

Supplementary Material