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The facial dysmorphology analysis technology in intellectual disability syndromes related to defects in the histones modifiers

Journal of Human Genetics volume 64, pages 721–728 (2019)Cite this article

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Abstract

Genetic syndromes are frequently associated with Intellectual Disability (ID), as well as craniofacial dysmorphisms. A group of ID syndromes with typical abnormal face related to chromatin remodeling defects, have been recognized, coining the term chromatinopathies. This is a molecular heterogeneous subset of congenital disorders caused by mutations of the various components of the Chromatin-Marking System (CMS), including modifiers of DNA and chromatin remodelers. We performed a phenotypic study on a sample of 120 individuals harboring variants in genes codifying for the histones enzymes, using the DeepGestalt technology. Three experiments (two multiclass comparison experiments and a frontal face-crop analysis) were conducted, analyzing respectively a total of 181 pediatric images in the first comparison experiment and 180 in the second, all individuals belonging predominantly to Caucasian population. The classification results were expressed in terms of the area under the curve (AUC) of the receiver-operating-characteristic curve (ROC). Significant values of AUC and low p-values were registered for all syndromes in the three experiments, in comparison with each other, with other ID syndromes characterized by recognizable craniofacial dysmorphisms and with unaffected controls. Final findings indicated that this group of diseases is characterized by distinctive dysmorphisms, which result pathognomonic. A correct interrogation and use of adequate informatics aids, could become a valid support for clinicians.

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Authors and Affiliations

  1. Medical Genetics Laboratory, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, Rome, Italy

    Giulia Pascolini, Alessandro Ferraris, Silvia Majore & Paola Grammatico

  2. FDNA Inc., Boston, MA, USA

    Nicole Fleischer

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  1. Giulia Pascolini
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  2. Nicole Fleischer
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Correspondence to Giulia Pascolini.

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Conflict of interest:

Nicole Fleischer is an employee of FDNA Inc., the company providing Face2Gene.

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Pascolini, G., Fleischer, N., Ferraris, A. et al. The facial dysmorphology analysis technology in intellectual disability syndromes related to defects in the histones modifiers. J Hum Genet 64, 721–728 (2019). https://doi.org/10.1038/s10038-019-0598-0

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  • DOI: https://doi.org/10.1038/s10038-019-0598-0

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