New Insights into Kleefstra Syndrome: Report of Two Novel Cases with Previously Unreported Features and Literature Review

Claudia Ciaccio, Giulietta Scuvera, Arianna Tucci, Barbara Gentilin, Marco Baccarin, Paola Marchisio, Sabrina Avignone, Donatella Milani

Research output: Contribution to journalArticle


Kleefstra syndrome (KS) is a rare genetic condition resulting from either 9q34.3 microdeletions or mutations in the EHMT1 gene located in the same genomic region. To date, approximately 100 patients have been reported, thereby allowing the core phenotype of KS to be defined as developmental delay/intellectual disability, generalized hypotonia, neuropsychiatric anomalies, and a distinctive facial appearance. Here, to further expand the knowledge on genotype and phenotype of this condition, we report 2 novel cases: one patient carrying a 46-kb 9q34.3 deletion and showing macrocephaly never described in KS, and a second patient carrying a classic 9q34.3 deletion, presenting with a previously unreported skeletal feature (postaxial polydactyly of the right foot) and an unusual brain anomaly (olfactory bulb hypoplasia) observed via magnetic resonance imaging. Further, we provide a review of the current literature regarding KS and compare these 2 patients with those previously described, thereby confirming that the genotype-phenotype correlation in KS remains difficult to determine.

Original languageEnglish
Pages (from-to)127-133
JournalCytogenetic and Genome Research
Issue number3
Publication statusPublished - 2018



  • 9q34.3
  • <italic>EHMT1</italic>
  • Developmental delay
  • Kleefstra syndrome
  • Olfactory bulbs
  • Polydactyly

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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