Expansion of the phenotypic and molecular spectrum of CWF19L1-related disorder

Clin Genet. 2023 May;103(5):566-573. doi: 10.1111/cge.14275. Epub 2023 Jan 11.

Abstract

Pathogenic variants in CWF19L1 lead to a rare autosomal recessive form of hereditary ataxia with only seven cases reported to date. Here, we describe four additional unrelated patients with biallelic variants in CWF19L1 (age range: 6-22 years) and provide a comprehensive review of the literature. The clinical spectrum was broad, including mild to profound global developmental delay; global or motor regression in infancy or adolescence; childhood-onset ataxia and cerebellar atrophy; and early-onset epilepsy. Since only two previously reported patients were adults, our cohort expands our understanding of the evolution of symptoms from childhood into early adulthood. Taken together, we describe that CWF19L1-related disorder presents with developmental and epileptic encephalopathy with treatment-resistant seizures and intellectual disability in childhood followed by progressive ataxia and other extrapyramidal movement disorders in adolescence.

Keywords: CWF19L1; ataxia; cerebellar malformation; epilepsy.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Adult
  • Cerebellar Ataxia* / diagnosis
  • Cerebellar Ataxia* / genetics
  • Cerebellar Diseases*
  • Child
  • Humans
  • Mutation
  • Nervous System Malformations*
  • Seizures
  • Spinocerebellar Degenerations*
  • Young Adult

Substances

  • CWF19L1 protein, human