Refining the Primrose syndrome phenotype: A study of five patients with ZBTB20 de novo variants and a review of the literature

Ruth Cleaver, Jonathan Berg, Emily Craft, Alison Foster, Richard J. Gibbons, Emma Hobson, Katherine Lachlan, Swati Naik, Julian R. Sampson, Saba Sharif, Sarah Smithson, Deciphering Developmental Disorders (DDD) Study, Michael J. Parker, Katrina Tatton-Brown (Lead / Corresponding author)

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13 Citations (Scopus)
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Primrose syndrome is a rare autosomal dominant condition caused by heterozygous missense variants within ZBTB20. Through an exome sequencing approach (as part of the Deciphering Developmental Disorders [DDD] study) we have identified five unrelated individuals with previously unreported, de novo ZBTB20 pathogenic missense variants. All five missense variants targeted the C2H2 zinc finger domains. This genotype-up approach has allowed further refinement of the Primrose syndrome phenotype. Major characteristics (>90% individuals) include an intellectual disability (most frequently in the moderate range), a recognizable facial appearance and brain MRI abnormalities, particularly abnormalities of the corpus callosum. Other frequent clinical associations (in 50–90% individuals) include sensorineural hearing loss (83%), hypotonia (78%), cryptorchidism in males (75%), macrocephaly (72%), behavioral issues (56%), and dysplastic/hypoplastic nails (57%). Based upon these clinical data we discuss our current management of patients with Primrose syndrome.

Original languageEnglish
Pages (from-to)344-349
Number of pages6
JournalAmerican Journal of Medical Genetics Part A
Issue number3
Early online date13 Jan 2019
Publication statusPublished - 1 Mar 2019


  • DDD study
  • exome sequencing
  • intellectual disability
  • Primrose syndrome
  • ZBTB20

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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