MYT1L-associated neurodevelopmental disorder: description of 40 new cases and literature review of clinical and molecular aspects

Hum Genet. 2022 Jan;141(1):65-80. doi: 10.1007/s00439-021-02383-z. Epub 2021 Nov 8.


Pathogenic variants of the myelin transcription factor-1 like (MYT1L) gene include heterozygous missense, truncating variants and 2p25.3 microdeletions and cause a syndromic neurodevelopmental disorder (OMIM#616,521). Despite enrichment in de novo mutations in several developmental disorders and autism studies, the data on clinical characteristics and genotype-phenotype correlations are scarce, with only 22 patients with single nucleotide pathogenic variants reported. We aimed to further characterize this disorder at both the clinical and molecular levels by gathering a large series of patients with MYT1L-associated neurodevelopmental disorder. We collected genetic information on 40 unreported patients with likely pathogenic/pathogenic MYT1L variants and performed a comprehensive review of published data (total = 62 patients). We confirm that the main phenotypic features of the MYT1L-related disorder are developmental delay with language delay (95%), intellectual disability (ID, 70%), overweight or obesity (58%), behavioral disorders (98%) and epilepsy (23%). We highlight novel clinical characteristics, such as learning disabilities without ID (30%) and feeding difficulties during infancy (18%). We further describe the varied dysmorphic features (67%) and present the changes in weight over time of 27 patients. We show that patients harboring highly clustered missense variants in the 2-3-ZNF domains are not clinically distinguishable from patients with truncating variants. We provide an updated overview of clinical and genetic data of the MYT1L-associated neurodevelopmental disorder, hence improving diagnosis and clinical management of these patients.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Epilepsy / genetics
  • Feeding and Eating Disorders / genetics
  • Female
  • Genetic Association Studies
  • Genetic Variation*
  • Heterozygote
  • Humans
  • Infant
  • Language Development Disorders / genetics
  • Male
  • Nerve Tissue Proteins / genetics*
  • Neurodevelopmental Disorders / genetics*
  • Obesity / genetics
  • Phenotype
  • Transcription Factors / genetics*
  • Young Adult


  • MYT1L protein, human
  • Nerve Tissue Proteins
  • Transcription Factors