Biallelic ZBTB11 Variants: A Neurodevelopmental Condition with Progressive Complex Movement Disorders

Mov Disord. 2024 Sep;39(9):1624-1630. doi: 10.1002/mds.29883. Epub 2024 Jun 20.

Abstract

Background: Biallelic ZBTB11 variants have previously been associated with an ultrarare subtype of autosomal recessive intellectual developmental disorder (MRT69).

Objective: The aim was to provide insights into the clinical and genetic characteristics of ZBTB11-related disorders (ZBTB11-RD), with a particular emphasis on progressive complex movement abnormalities.

Methods: Thirteen new and 16 previously reported affected individuals, ranging in age from 2 to 50 years, with biallelic ZBTB11 variants underwent clinical and genetic characterization.

Results: All patients exhibited a range of neurodevelopmental phenotypes with varying severity, encompassing ocular and neurological features. Eleven new patients presented with complex abnormal movements, including ataxia, dystonia, myoclonus, stereotypies, and tremor, and 7 new patients exhibited cataracts. Deep brain stimulation was successful in treating 1 patient with generalized progressive dystonia. Our analysis revealed 13 novel variants.

Conclusions: This study provides additional insights into the clinical features and spectrum of ZBTB11-RD, highlighting the progressive nature of movement abnormalities in the background of neurodevelopmental phenotype.

Keywords: ZBTB11; cataracts; deep brain stimulation; movement disorders.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Male
  • Middle Aged
  • Movement Disorders* / genetics
  • Neurodevelopmental Disorders / genetics
  • Phenotype
  • Repressor Proteins / genetics
  • Young Adult

Substances

  • Repressor Proteins
  • ZBTB11 protein, human