Females with de novo aberrations in PHF6: Clinical overlap of Borjeson–Forssman–Lehmann with Coffin–Siris syndrome


  • Christiane Zweier,

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    • Christiane Zweier is Human Geneticist at the Institute of Human Genetics of the Friedrich-Alexander-Universität Erlangen-Nürnberg in Erlangen, Germany. Her research interests are mainly the clinical, genetic and functional elucidation of intellectual disability and dysmorphology disorders.
  • Olaf Rittinger,

  • Ingrid Bader,

  • Siren Berland,

  • Trevor Cole,

  • Franziska Degenhardt,

  • Nataliya Di Donato,

  • Luitgard Graul-Neumann,

  • Juliane Hoyer,

  • Sally Ann Lynch,

  • Ingrid Vlasak,

  • Dagmar Wieczorek

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    • Dagmar Wieczorek is a Human Geneticist at the Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Germany. Her main interests are clinical and molecular aspects of intellectual disability and craniofacial disorders.

  • Conflict of interest: The authors declare that they have no conflicts of interest.

Correspondence to: Christiane Zweier, Institute of Human Genetics, Schwabachanlage 10, 91054 Erlangen, Germany.

E-mail: christiane.zweier@uk-erlangen.de


Recently, de novo aberrations in PHF6 were identified in females with intellectual disability and with a distinct phenotype including a characteristic facial gestalt with bitemporal narrowing, prominent supraorbital ridges, synophrys, a short nose and dental anomalies, tapering fingers with brachytelephalangy, clinodactyly and hypoplastic nails, short toes with hypoplastic nails, and linear skin hyperpigmentation. In adolescent or older patients, this phenotype overlaps but is not identical with Borjeson–Forssman–Lehmann syndrome in males, caused by X-linked recessive mutations in PHF6. In younger girls there seems to be a striking phenotypic overlap with Coffin–Siris syndrome, which is characterized by intellectual disability, sparse hair and hypoplastic nails. This review will summarize and characterize the female phenotype caused by de novo aberrations in PHF6 and will discuss the overlapping and distinguishing features with Coffin–Siris syndrome. © 2014 Wiley Periodicals, Inc.