Genotype-Phenotype Correlations in Children with HHT

Alexandra Kilian, Toronto HHT Centre, St. Michael's Hospital and Li Ka Shing Knowledge Institute, Toronto, ON M5B 1W8, Canada.
Giuseppe A. Latino, Toronto HHT Centre, St. Michael's Hospital and Li Ka Shing Knowledge Institute, Toronto, ON M5B 1W8, Canada.
Andrew J. White, Washington University School of Medicine, St Louis, MO 63110, USA.
Dewi Clark, Toronto HHT Centre, St. Michael's Hospital and Li Ka Shing Knowledge Institute, Toronto, ON M5B 1W8, Canada.
Murali M. Chakinala, Washington University School of Medicine, St Louis, MO 63110, USA.
Felix Ratjen, Division of Respiratory Medicine and Translational Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
Jamie McDonald, University of Utah Health, Salt Lake City, UT 84132, USA.
Kevin Whitehead, University of Utah Health, Salt Lake City, UT 84132, USA.
James R. Gossage, Augusta University Health, Augusta, GA 30912, USA.
Doris Lin, Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Katharine Henderson, Department of Radiology and Biomedical Imaging, and HHT Program, Yale University School of Medicine, New Haven, CT 06510, USA.
Jeffrey Pollak, Department of Radiology and Biomedical Imaging, and HHT Program, Yale University School of Medicine, New Haven, CT 06510, USA.
Justin P. McWilliams, Department of Interventional Radiology, University of California Los Angeles, Los Angeles, CA 90095, USA.
Helen Kim, USA Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA 94110, USA.
Michael T. Lawton, Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ 85013, USA.Follow
Marie E. Faughnan, Toronto HHT Centre, St. Michael's Hospital and Li Ka Shing Knowledge Institute, Toronto, ON M5B 1W8, Canada.

Document Type

Article

Abstract

Hereditary hemorrhagic telangiectasia (HHT), a rare autosomal dominant disease mostly caused by mutations in three known genes (, , and ), is characterized by the development of vascular malformations (VMs). Patients with HHT may present with mucocutaneous telangiectasia, as well as organ arteriovenous malformations (AVMs) of the central nervous system, lungs, and liver. Genotype-phenotype correlations have been well described in adults with HHT. We aimed to investigate genotype-phenotype correlations among pediatric HHT patients. Demographic, clinical, and genetic data were collected and analyzed in 205 children enrolled in the multicenter Brain Vascular Malformation Consortium HHT Project. A chi-square test was used to determine the association between phenotypic presentations and genotype. Among 205 patients (age range: 0-18 years; mean: 11 years), mutation was associated with the presence of pulmonary AVMs ( < 0.001) and brain VM ( < 0.001). The presence of a combined phenotype-defined as both pulmonary AVMs and brain VMs-was also associated with mutation. Gastrointestinal bleeding was rare (4.4%), but was associated with genotype ( < 0.001). We conclude that genotype-phenotype correlations among pediatric HHT patients are similar to those described among adults. Specifically, pediatric patients with mutation have a greater prevalence of pulmonary AVMs, brain VMs, and a combined phenotype.

Publication Date

8-28-2020

Publication Title

Journal of clinical medicine

ISSN

2077-0383

Volume

9

Issue

9

PubMed ID

32842615

Digital Object Identifier (DOI)

10.3390/jcm9092714

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