Genotype-Phenotype Correlations in Children with HHT.

Autor: Kilian A; Toronto HHT Centre, St. Michael's Hospital and Li Ka Shing Knowledge Institute, Toronto, ON M5B 1W8, Canada., Latino GA; Toronto HHT Centre, St. Michael's Hospital and Li Ka Shing Knowledge Institute, Toronto, ON M5B 1W8, Canada.; Department of Pediatrics, North York General Hospital, University of Toronto, Toronto, ON M2K 1E1, Canada., White AJ; Washington University School of Medicine, St Louis, MO 63110, USA., Clark D; Toronto HHT Centre, St. Michael's Hospital and Li Ka Shing Knowledge Institute, Toronto, ON M5B 1W8, Canada.; Division of Respirology, Department of Medicine, University of Toronto, Toronto, ON M5S 3H2, Canada., Chakinala MM; Washington University School of Medicine, St Louis, MO 63110, USA., Ratjen F; Division of Respiratory Medicine and Translational Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada., McDonald J; University of Utah Health, Salt Lake City, UT 84132, USA., Whitehead K; University of Utah Health, Salt Lake City, UT 84132, USA., Gossage JR; Augusta University Health, Augusta, GA 30912, USA., Lin D; Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Henderson K; Department of Radiology and Biomedical Imaging, and HHT Program, Yale University School of Medicine, New Haven, CT 06510, USA., Pollak J; Department of Radiology and Biomedical Imaging, and HHT Program, Yale University School of Medicine, New Haven, CT 06510, USA., McWilliams JP; Department of Interventional Radiology, University of California Los Angeles, Los Angeles, CA 90095, USA., Kim H; USA Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA 94110, USA.; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94143, USA.; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94158, USA., Lawton MT; Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ 85013, USA., Faughnan ME; Toronto HHT Centre, St. Michael's Hospital and Li Ka Shing Knowledge Institute, Toronto, ON M5B 1W8, Canada.; Division of Respirology, Department of Medicine, University of Toronto, Toronto, ON M5S 3H2, Canada.
Jazyk: angličtina
Zdroj: Journal of clinical medicine [J Clin Med] 2020 Aug 22; Vol. 9 (9). Date of Electronic Publication: 2020 Aug 22.
DOI: 10.3390/jcm9092714
Abstrakt: Hereditary hemorrhagic telangiectasia (HHT), a rare autosomal dominant disease mostly caused by mutations in three known genes ( ENG , ACVRL1 , and SMAD4 ), 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), ENG mutation was associated with the presence of pulmonary AVMs ( p < 0.001) and brain VM ( p < 0.001). The presence of a combined phenotype-defined as both pulmonary AVMs and brain VMs-was also associated with ENG mutation. Gastrointestinal bleeding was rare (4.4%), but was associated with SMAD4 genotype ( p < 0.001). We conclude that genotype-phenotype correlations among pediatric HHT patients are similar to those described among adults. Specifically, pediatric patients with ENG mutation have a greater prevalence of pulmonary AVMs, brain VMs, and a combined phenotype.
Databáze: MEDLINE