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Pascolini. J Transl Genet Genom 2020;4:17-21 Journal of Translational
DOI: 10.20517/jtgg.2020.05 Genetics and Genomics

Original Article Open Access

DeepGestalt analysis of the SETD5-associated
intellectual disability syndrome

Giulia Pascolini

Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, Rome 00152, Italy.
Correspondence to: Dr. Giulia Pascolini, Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-
Forlanini Hospital, Circonvallazione Gianicolense 87, Rome 00152, Italy. E-mail: giupascolini@gmail.com

How to cite this article: Pascolini G. DeepGestalt analysis of the SETD5-associated intellectual disability syndrome. J Transl Genet
Genom 2020;4:17-21. https://doi.org/10.20517/jtgg.2020.05
Received: 30 Jan 2020 First Decision: 28 Feb 2020 Revised: 16 Mar 2020 Accepted: 18 Mar 2020 Published: 30 Mar 2020

Science Editor: Tjitske Kleefstra Copy Editor: Jing-Wen Zhang Production Editor: Tian Zhang

Abstract
Aim: This is the first computer-assisted study focused on the craniofacial features of the intellectual disability (ID)/
developmental delay (DD) syndrome related to haploinsufficiency of the SETD5 gene (SET domain-containing protein
5, MIM#615743), which is a chromatin regulator. The purpose of this novel research is to better delineate the facial
phenotype of this condition and identify the associated dysmorphic features to consider for clinical diagnosis.

Methods: A total of 18 2D frontal images of previously published pediatric individuals (aged 1-14 years, Caucasian
ethnicity) with SETD5 mutations (SETD5, cohort 1) were uploaded to the RESEARCH application of the Face2Gene online
platform (V.19.1.3) (FDNA Inc., Boston, MA, USA). Images from this group of patients were compared with 36 photos of
individuals with two other known chromatin disorders, specifically KBG (KBGS, cohort 2, 18 images) and Koolen-de Vries
syndromes (KdVS, cohort 3, 18 images), which share with the SETD5-related ID syndrome a very similar facial gestalt
and peculiar dysmorphisms. An additional cohort of 18 unaffected controls that were matched for age and ethnicity
(Ctrl., controls, cohort 4) was also included in the comparison experiment.

Results: Results obtained from the binary comparison analysis were expressed in terms of Area Under the Curve and
its Receiver Operating Characteristic curve for aggregated splits. A high facial overlap between the SETD5 -related
phenotype and KBGS was demonstrated. Other conditions considered for the study were well recognized by the system
and differentiated using the unaffected controls.

Conclusion: This study confirms the presence of distinctive dysmorphic features that characterize the SETD5-related
facial phenotype, providing observations about its possible role in facial morphogenesis.

Keywords: SETD5, dysmorphisms, intellectual disability, chromatin, Face2Gene

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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