title: Clinical and genetic challenges in a family with history of childhood polyp, aortopathy, and clinical diagnosis of hereditary hemorrhagic teleangiectasia (HHT).
abstract: Hereditary hemorrhagic teleangiectasia (HHT) is a genetic disorder, characterized by abnormal vessel formation and arteriovenous malformations (AVMs). The so-called "Curaçao criteria" are most commonly employed for the purposes of clinical diagnosis. However, children may not exhibit the full magnitude of symptoms and the Curaçao criteria appear to be less sensitive in this setting. We describe a family, in which two members were clinically diagnosed with HHT and referred for genetic testing. As there were phenotypic features suggesting the high likelihood of combined syndrome of juvenile polyposis with hereditary hemorrhagic teleangiectasia (JPHT), we proceeded with genetic testing of SMAD4 gene as initial step, which revealed a novel frameshift mutation. This case shows the variety of challenges that clinicians and genetic laboratories may face in complex cases such as combined JPHT syndrome. Knowledge of the syndrome features is of paramount importance as they could frequently point at the most appropriate gene to be tested.
authors.affiliation: Department of Medical Chemistry and Biochemistry, Genetic Medico-Diagnostic Laboratory Genica, Sofia Medical University, Sofia, Bulgaria.
authors.forename: Tanya
authors.initials: T
authors.lastname: Kadiyska
authors.affiliation: Department of Cardiology, University Hospital Lozenets, Sofia, Bulgaria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Nossikoff
authors.affiliation: St. Ekaterina University Hospital, Sofia, Bulgaria.
authors.forename: Pencho
authors.initials: P
authors.lastname: Kratunkov
authors.affiliation: University Hospital "St. Marina", Varna, Bulgaria.
authors.forename: Mary
authors.initials: M
authors.lastname: Hachmerian
authors.affiliation: University Hospital "St. Marina", Varna, Bulgaria.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Angelova
keywords: Hereditary hemorrhagic teleangiectasia (HHT); SMAD4; juvenile polyposis; juvenile polyposis hereditary hemorrhagic teleangiectasia (JPHT)