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Using deep-neural-network-driven facial recognition to identify distinct Kabuki syndrome 1 and 2 gestalt


Kabuki syndrome (KS) is a rare genetic disorder caused by mutations in two major genes, KMT2D and KDM6A, that are responsible for Kabuki syndrome 1 (KS1, OMIM147920) and Kabuki syndrome 2 (KS2, OMIM300867), respectively. We lack a description of clinical signs to distinguish KS1 and KS2. We used facial morphology analysis to detect any facial morphological differences between the two KS types. We used a facial-recognition algorithm to explore any facial morphologic differences between the two types of KS. We compared several image series of KS1 and KS2 individuals, then compared images of those of Caucasian origin only (12 individuals for each gene) because this was the main ethnicity in this series. We also collected 32 images from the literature to amass a large series. We externally validated results obtained by the algorithm with evaluations by trained clinical geneticists using the same set of pictures. Use of the algorithm revealed a statistically significant difference between each group for our series of images, demonstrating a different facial morphotype between KS1 and KS2 individuals (mean area under the receiver operating characteristic curve = 0.85 [p = 0.027] between KS1 and KS2). The algorithm was better at discriminating between the two types of KS with images from our series than those from the literature (p = 0.0007). Clinical geneticists trained to distinguished KS1 and KS2 significantly recognised a unique facial morphotype, which validated algorithm findings (p = 1.6e−11). Our deep-neural-network-driven facial-recognition algorithm can reveal specific composite gestalt images for KS1 and KS2 individuals.

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Fig. 1: On the left is the score distribution for KDM6A vs KMT2D, and on the right is the ROC curve obtained by using DeepGestalt analysis.
Fig. 2: On the left is the score distribution for KDM6A vs KMT2D, and on the right is the ROC curve obtained by using DeepGestalt analysis.
Fig. 3:  On the left is the composite gestalt based upon 17 KDM6A individual’s pictures form our collaborative dataset, and on the right is the composite gestalt based upon 17 KMT2D individual’s pictures from our collaborative dataset.
Fig. 4: Distribution of scores for each subgroup of clinicians in differentiating between KS1 and KS2 individuals (n = 60).

Data availability

The data (patient’s facial pictures) that supports the findings of this study are available from the French research program PHRC AOM-09-070 (ClinicalTrials. gov identifier: NCT01314534), but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of patients and physicians in charge of the patients.


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We deeply thank all clinicians and biologists involved in diagnostic and data sharing for this study. We thank the French Kabuki Association for their help for this study. We thank Nicole Fleischer and Sarah Savage for advice and assistance related to the algorithm for this project.


Part of this work was supported by the French Ministry of Health (Programme Hospitalier de Recherche Clinique national, AOM 07-090), Fondation Maladies Rares, and the French Kabuki Association

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Correspondence to David Genevieve.

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DG was a consultant for the Takeda Society in 2018. Takeda did not have any role in this study.

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All clinical geneticist consents for participation were obtained through a survey where their responses were also collected.

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Rouxel, F., Yauy, K., Boursier, G. et al. Using deep-neural-network-driven facial recognition to identify distinct Kabuki syndrome 1 and 2 gestalt. Eur J Hum Genet 30, 682–686 (2022).

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