Impact Factor 3.517
2018 JCR, Web of Science Group 2019

Frontiers journals are at the top of citation and impact metrics

Case Report ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.00650


  • 1Fondazione Istituto Neurologico Nazionale Casimiro Mondino (IRCCS), Italy
  • 2Pisana University Hospital, Italy
  • 3University of Pisa, Italy

We report on a 34-year old woman and her mother who both have clinical features suggestive for otofaciocervical syndrome (OTFCS), a disorder characterized by a combination of facial dysmorphisms , ear abnormalities with hearing loss and shoulder girdle anomalies.
OTFCS presents overlapping features with branchiootorenal spectrum disorders , including branchiootorenal syndrome and branchiootic syndrome .
These disorders have been described as clinically distinct entities, but molecular studies have shown
that all the causative genes belong to Pax-Six-Eya-Dach network (PSEDN).
So far, the genetic diagnosis of OTFC has been performed only in very few cases and involves two genes, EYA1 and PAX1, thus it is likely that other genes have still to be identified.
In present patient, array CGH analysis showed a 3.7 Mb deletion in 6q23; a smaller 1.9 Mb deletion in the same region was detected in her mother. The minimal overlapping region harbours the EYA4 gene.
The cases here described are interesting, since they all showed the typical clinical features of OTFCS, associated to a deletion in 6q23.2. Even if we can not exclude the contribution of other genes to the phenotype, EYA4 is a good candidate for OTFCS according to its pattern of expression, its sequence similarity to EYA1, and its involvement in PSEDN.

Keywords: EYA4 gene, EYA1 gene, otofacialcervical syndrome, 6q23 deletion, Array CGH (aCGH)

Received: 19 Nov 2018; Accepted: 19 Jun 2019.

Edited by:

Nagwa E. Gaboon, Faculty of Medicine, Ain Shams University, Egypt

Reviewed by:

Ludmila Matyakhina, GeneDx, United States
Leda Torres, National Institute of Pediatrics (Mexico), Mexico  

Copyright: © 2019 gana, Valetto, Toschi, sardelli, cappelli, Peroni and Bertini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Angelo Valetto, Pisana University Hospital, Pisa, 56124, Tuscany, Italy,