Clinical spectrum of Kabuki-like syndrome caused by HNRNPK haploinsufficiency

Maria Lisa Dentici, Sabina Barresi, Marcello Niceta, Francesca Pantaleoni, Simone Pizzi, Bruno Dallapiccola, Marco Tartaglia, Maria Cristina Digilio

Research output: Contribution to journalArticlepeer-review


Kabuki syndrome is a genetically heterogeneous disorder characterized by postnatal growth retardation, skeletal abnormalities, intellectual disability, facial dysmorphisms and a variable range of organ malformations. In ~30% of affected individuals, the underlying genetic defect remains unknown. A small number of inactivating heterozygous HNRNPK mutations has recently been reported to be associated with a condition partially overlapping or suggestive of Kabuki syndrome. Here, we report on an 11-year-old girl with a complex phenotype in whom the diagnosis of KS was suggested but molecular testing for the known causative disease genes was negative. Whole-exome sequencing identified a previously undescribed de novo truncating mutation in HNRNPK as the molecular defect underlying the trait. Analysis of available records of patients with HNRNPK haploinsufficiency was performed to delineate the associated clinical phenotype and outline their distinguishing features in comparison with the KS clinical spectrum. The clinical profile associated with inactivating HNRNPK mutations supports the idea that the associated disorder should be considered as a distinct nosologic entity clinically related to KS, and that the condition should be considered in differential diagnosis with KS, in particular in subjects exhibiting brain malformation (nodular heterotopia), craniosynostosis, and polydactyly.

Original languageEnglish
Pages (from-to)401-407
Number of pages7
JournalClinical Genetics
Issue number2
Publication statusPublished - Apr 25 2017


  • craniosynostosis
  • exome
  • Kabuki syndrome
  • nodular heterotopia
  • polydactyly

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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