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

Neuropediatrics. 2019 Oct;50(5):327-331. doi: 10.1055/s-0039-1692141. Epub 2019 Jul 18.

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.

MeSH terms

  • Child
  • Dystonic Disorders / complications
  • Dystonic Disorders / diagnosis*
  • Dystonic Disorders / genetics
  • Epilepsies, Myoclonic / complications
  • Epilepsies, Myoclonic / diagnosis*
  • Epilepsies, Myoclonic / genetics
  • Humans
  • Male
  • Mental Retardation, X-Linked / complications
  • Mental Retardation, X-Linked / diagnosis*
  • Mental Retardation, X-Linked / genetics
  • Mutation
  • Puberty, Precocious / complications
  • Puberty, Precocious / diagnosis*
  • Puberty, Precocious / genetics
  • Siblings
  • X-linked Nuclear Protein / genetics*
  • alpha-Thalassemia / complications
  • alpha-Thalassemia / diagnosis*
  • alpha-Thalassemia / genetics

Substances

  • ATRX protein, human
  • X-linked Nuclear Protein

Supplementary concepts

  • ATR-X syndrome
  • Myoclonic dystonia