Mutations in VLDLR as a cause for autosomal recessive cerebellar ataxia with mental retardation (Dysequilibrium syndrome)

Kym M. Boycott, Carsten Bonnemann, Joachim Herz, Stephanie Neuert, Chandree Beaulieu, James N. Scott, Anuradha Venkatasubramanian, Jillian S. Parboosingh

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Dysequilibrium syndrome is a genetically heterogeneous condition that combines autosomal recessive, nonprogressive cerebellar ataxia with mental retardation. Here, we report the first patient heterozygous for 2 novel mutations in VLDLR. An 18-month-old girl presented with significant hypotonia, global developmental delay, and truncal and peripheral ataxia. Magnetic resonance imaging of the brain demonstrated hypoplasia of the inferior cerebellar vermis and hemispheres, small pons, and a simplified cortical sulcation pattern. Sequence analysis of the VLDLR gene identified a nonsense and missense mutation. Six mutations in VLDLR have now been identified in 5 families with a phenotype characterized by moderate-to-profound mental retardation, delayed ambulation, truncal and peripheral ataxia, and occasional seizures. Neuroanatomically, the loss-of-function effect of the different mutations is indistinguishable. VLDLR-associated cerebellar hypoplasia is emerging as a panethnic, clinically, and molecularly well-defined genetic syndrome.

Original languageEnglish (US)
Pages (from-to)1310-1315
Number of pages6
JournalJournal of Child Neurology
Volume24
Issue number10
DOIs
Publication statusPublished - 2009

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Keywords

  • Cerebellar hypoplasia
  • Dysequilibrium syndrome
  • VLDLR

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health

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