TY - JOUR
T1 - Genotype–phenotype correlations in children with hht
AU - the Brain Vascular Malformation Consortium HHT Investigator Group
AU - Kilian, Alexandra
AU - Latino, Giuseppe A.
AU - White, Andrew J.
AU - Clark, Dewi
AU - Chakinala, Murali M.
AU - Ratjen, Felix
AU - McDonald, Jamie
AU - Whitehead, Kevin
AU - Gossage, James R.
AU - Lin, Doris
AU - Henderson, Katharine
AU - Pollak, Jeffrey
AU - McWilliams, Justin P.
AU - Kim, Helen
AU - Lawton, Michael T.
AU - Faughnan, Marie E.
AU - Chakinala, Murali
AU - Clancy, Marianne S.
AU - Gossage, James R.
AU - Henderson, Katharine
AU - Iyer, Vivek
AU - Kasthuri, Raj S.
AU - Kim, Helen
AU - Krings, Timo
AU - Lawton, Michael T.
AU - Lin, Doris
AU - Mager, Johannes Jurgen
AU - Marchuk, Douglas A.
AU - McWilliams, Justin P.
AU - McDonald, Jamie
AU - Pawlikowska, Ludmila
AU - Pollak, Jeffrey
AU - Ratjen, Felix
AU - Swanson, Karen
AU - Vethanayagam, Dilini
AU - Wilcox, Pearce
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/9
Y1 - 2020/9
N2 - 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.
AB - 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.
KW - ACVRL1
KW - Arteriovenous malformation
KW - ENG
KW - Genotype–phenotype correlation
KW - Hereditary hemorrhagic telangiectasia
KW - Pediatrics
KW - SMAD4
UR - http://www.scopus.com/inward/record.url?scp=85112496387&partnerID=8YFLogxK
U2 - 10.3390/jcm9092714
DO - 10.3390/jcm9092714
M3 - Article
AN - SCOPUS:85112496387
SN - 2077-0383
VL - 9
SP - 1
EP - 9
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
IS - 9
M1 - 2714
ER -