14q22.3 duplication including OTX2 in a girl with medulloblastoma: A case report with literature review

Am J Med Genet A. 2024 Jul;194(7):e63604. doi: 10.1002/ajmg.a.63604. Epub 2024 Mar 21.

Abstract

Orthodenticle homeobox 2 (OTX2) is a known oncogenic driver of medulloblastoma. Germline duplication of 14q22.3 including OTX2 is a rare condition reported in patients with combined pituitary hormone deficiency, oculo-auriculo-vertebral spectrum, and hemifacial microsomia. There has been one previously published case of a patient carrying a 14q22.3 duplication that included OTX2 with hemifacial microsomia who also developed medulloblastoma. Here, we present a case of a 6-year-old girl with a history of delayed development who was diagnosed with medulloblastoma. Genetic evaluations revealed that she inherited a germline duplication of 14q22.3, which included OTX2. This genetic alteration was passed down from her mother, who also had a history of delayed development. Results from other genetic testing, including exome sequencing, fragile X syndrome, and mtDNA testing, were negative/normal. This is the second report of a 14q22.3 duplication that included OTX2 in a patient with medulloblastoma. Further studies are necessary to establish a clear association.

Keywords: 14q22.3 duplication; OTX2; delayed development; medulloblastoma.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Cerebellar Neoplasms / diagnosis
  • Cerebellar Neoplasms / genetics
  • Cerebellar Neoplasms / pathology
  • Child
  • Chromosome Duplication / genetics
  • Chromosomes, Human, Pair 14 / genetics
  • Female
  • Humans
  • Medulloblastoma* / genetics
  • Medulloblastoma* / pathology
  • Otx Transcription Factors* / genetics

Substances

  • Otx Transcription Factors
  • OTX2 protein, human