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Facial clues to the photosensitive trichothiodystrophy phenotype in childhood

Journal of Human Genetics volume 68, pages 437–443 (2023)Cite this article

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Abstract

Among genodermatoses, trichothiodystrophies (TTDs) are a rare genetically heterogeneous group of syndromic conditions, presenting with skin, hair, and nail abnormalities. An extra-cutaneous involvement (craniofacial district and neurodevelopment) can be also a part of the clinical picture. The presence of photosensitivity describes three forms of TTDs: MIM#601675 (TTD1), MIM#616390 (TTD2) and MIM#616395 (TTD3), that are caused by variants afflicting some components of the DNA Nucleotide Excision Repair (NER) complex and with more marked clinical consequences. In the present research, 24 frontal images of paediatric patients with photosensitive TTDs suitable for facial analysis through the next-generation phenotyping (NGP) technology were obtained from the medical literature. The pictures were compared to age and sex-matched to unaffected controls using 2 distinct deep-learning algorithms: DeepGestalt and GestaltMatcher (Face2Gene, FDNA Inc., USA). To give further support to the observed results, a careful clinical revision was undertaken for each facial feature in paediatric patients with TTD1 or TTD2 or TTD3. Interestingly, a distinctive facial phenotype emerged by the NGP analysis delineating a specific craniofacial dysmorphic spectrum. In addition, we tabulated every single detail within the observed cohort. The novelty of the present research includes the facial characterization in children with the photosensitive types of TTDs through the 2 different algorithms. This result can become additional criteria for early diagnosis, and for subsequent targeted molecular investigations as well as a possible tailored multidisciplinary personalized management.

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Fig. 1

Data availability

Data regarding this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors thank Nicole Fleischer and Carolina Alves, for their technical support in performing the DeepGestalt and GestaltMatcher experiments.

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Authors and Affiliations

  1. Pediatric Cardiology and Arrhythmia/Syncope Units, Bambino Gesù Children Hospital and Research Institute, Rome, Italy

    Giulia Pascolini & Anwar Baban

  2. Rare Diseases Unit, Istituto Dermopatico dell’Immacolata, IDI-IRCCS, Rome, Italy

    Giulia Pascolini

  3. Medical Genetics Division, Department of Experimental Medicine, Sapienza University, Policlinico Umberto I Hospital, Rome, Italy

    Federica Gaudioso

  4. Legal Genetics, Rome, Italy

    Marina Baldi

  5. Pediatrics and Neonatology Unit, ASL RM4, San Paolo Hospital, Civitavecchia, Rome, Italy

    Dario Alario & Francesco Dituri

  6. Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy

    Antonio Novelli

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  1. Giulia Pascolini
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  2. Federica Gaudioso
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  3. Marina Baldi
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Correspondence to Giulia Pascolini.

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The authors declare no competing interests.

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This study was performed according to the Helsinki declaration. Approval from an internal review board was not necessary since the study is based on literature revision.

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Pascolini, G., Gaudioso, F., Baldi, M. et al. Facial clues to the photosensitive trichothiodystrophy phenotype in childhood. J Hum Genet 68, 437–443 (2023). https://doi.org/10.1038/s10038-023-01134-4

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  • DOI: https://doi.org/10.1038/s10038-023-01134-4

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