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Alazami syndrome: the first case of papillary thyroid carcinoma

Journal of Human Genetics volume 65, pages 133–141 (2020)Cite this article

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Abstract

Alazami syndrome (MIM#615071) is a rare developmental disorder caused by biallelic variants in the LARP7 gene. Hallmark features include short stature, global developmental delay, and distinctive facial features. To date, 23 patients from 11 families have been reported in the literature. Here we describe a 19-year-old man who, in association with the typical features of Alazami syndrome, was diagnosed at the age of 14 years with papillary thyroid carcinoma, harboring the somatic BRAF V600E mutation. Whole exome sequencing revealed two novel LARP7 variants in compound heterozygosity, whereas only common variants were detected in genes associated with familial nonmedullary thyroid cancer (MIM#188550). LARP7 acts as a tumor suppressor in breast and gastric cancer, and possibly, according to recent studies, in thyroid tumors. Since thyroid cancer is rare among children and adolescents, we hypothesize that the LARP7 variants identified in our patient are responsible for both Alazami syndrome and tumor susceptibility. We also provide an overview of the clinical findings in all Alazami syndrome patients reported to date and discuss the possible pathogenetic mechanism that may underlie this condition, including the role of LARP7 in tumor susceptibility.

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Acknowledgements

The authors thank ‘Fondazione Cassa di Risparmio Reggio Emilia Pietro Manodori’ for financial support. The authors would also like to thank the patient’s family for providing medical data and photographs, photographers Marco Bonazzi and Luca Valcavi, Federica Torricelli for bioinformatic counseling, and genetic nurse Maria Claudia Menozzi. The authors are deeply grateful to the Biobank of the Laboratory of Human Genetics (Director: Domenico Coviello) of the IRCCS Istituto Giannina Gaslini (Genova, Italy), a part of the Telethon Network of Genetic Biobanks. Written consent for publication of the clinical pictures was obtained from the patient’s parents.

Authors contribution

LG and II conceived the study. LG, II, EM, SR, MP, SP, DN, CB, AF, and SB were crucial for acquiring the patient’s clinical data. LM carried out whole exome sequencing and sequence alignment. SGC performed WES data analysis and variant confirmation testing. II, SGC, EM, SP, DN, CB, AF, LG, and OZ have been involved in drafting the paper and revising it critically. All the authors have given final approval.

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Author notes

  1. These authors contributed equally: Ivan Ivanovski, Stefano Giuseppe Caraffi

Authors and Affiliations

  1. Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy

    Ivan Ivanovski, Stefano Giuseppe Caraffi, Simonetta Rosato, Marzia Pollazzon & Livia Garavelli

  2. Department of Surgical, Medical, Dental and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy

    Ivan Ivanovski

  3. Endocrinology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy

    Elisa Magnani & Andrea Frasoldati

  4. CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

    Leslie Matalonga

  5. Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy

    Simonetta Piana

  6. Laboratory of Molecular Biology, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy

    Davide Nicoli

  7. Laboratory of Human Genetics, IRCCS Istituto Giannina Gaslini, Genova, Italy

    Chiara Baldo

  8. Department of Pediatrics, University of Parma, Parma, Italy

    Sergio Bernasconi

  9. Department of Molecular Medicine, University of Pavia, Pavia, Italy

    Orsetta Zuffardi

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  1. Ivan Ivanovski
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Correspondence to Livia Garavelli.

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Ivanovski, I., Caraffi, S.G., Magnani, E. et al. Alazami syndrome: the first case of papillary thyroid carcinoma. J Hum Genet 65, 133–141 (2020). https://doi.org/10.1038/s10038-019-0682-5

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