TY - JOUR
T1 - Brain arteriovenous malformations associated with hereditary hemorrhagic telangiectasia
T2 - Gene-phenotype correlations
AU - Nishida, Takeo
AU - Faughnan, Marie E.
AU - Krings, Timo
AU - Chakinala, Murali
AU - Gossage, James R.
AU - Young, William L.
AU - Kim, Helen
AU - Pourmohamad, Tony
AU - Henderson, Katharine J.
AU - Schrum, Stacy D.
AU - James, Melissa
AU - Quinnine, Nancy
AU - Bharatha, Aditya
AU - terBrugge, Karel G.
AU - White, Robert I.
PY - 2012/11
Y1 - 2012/11
N2 - Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disease with a wide spectrum of vascular malformations (VMs) involving multiple organs. Nine to 16% of patients with HHT harbor brain arteriovenous malformations (AVMs), which can cause intracranial hemorrhage (ICH). Our objective was to study clinical manifestations of brain AVMs in patients with HHT and correlate these with the specific gene mutated. We reviewed records of 171 patients with HHT and brain AVMs. A history of ICH was found in 27% (41/152) patients, with a mean age of 26±18 range, (0-68) years. All of patients with ICH were neurologically asymptomatic prior to ICH. Multiple brain AVMs were found in 23% (170/39) of patients on initial examination. Genetic test results were available in 109 (64%) patients. Mutations in ENG, ACVRL1, and SMAD4 were present in 75 (69%), 18 (17%), and 2 (2%), respectively. A history of ICH was reported in 24% of patients with an ENG mutation and 27% of patients with an ACVRL1 mutation, with a mean age of 26±16 (range, 2-50) and 18±21 (0-48) years, respectively. No statistically significant differences in age at first brain AVM diagnosis, prevalence of ICH history, age at ICH, or other manifestations of brain AVMs were observed among gene groups. In conclusion, no evidence for differences in brain AVM characteristics was observed among HHT gene groups, although we cannot exclude clinically important differences. Larger studies are needed to further guide brain AVM screening decisions in patients with HHT.
AB - Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disease with a wide spectrum of vascular malformations (VMs) involving multiple organs. Nine to 16% of patients with HHT harbor brain arteriovenous malformations (AVMs), which can cause intracranial hemorrhage (ICH). Our objective was to study clinical manifestations of brain AVMs in patients with HHT and correlate these with the specific gene mutated. We reviewed records of 171 patients with HHT and brain AVMs. A history of ICH was found in 27% (41/152) patients, with a mean age of 26±18 range, (0-68) years. All of patients with ICH were neurologically asymptomatic prior to ICH. Multiple brain AVMs were found in 23% (170/39) of patients on initial examination. Genetic test results were available in 109 (64%) patients. Mutations in ENG, ACVRL1, and SMAD4 were present in 75 (69%), 18 (17%), and 2 (2%), respectively. A history of ICH was reported in 24% of patients with an ENG mutation and 27% of patients with an ACVRL1 mutation, with a mean age of 26±16 (range, 2-50) and 18±21 (0-48) years, respectively. No statistically significant differences in age at first brain AVM diagnosis, prevalence of ICH history, age at ICH, or other manifestations of brain AVMs were observed among gene groups. In conclusion, no evidence for differences in brain AVM characteristics was observed among HHT gene groups, although we cannot exclude clinically important differences. Larger studies are needed to further guide brain AVM screening decisions in patients with HHT.
KW - Brain arteriovenous malformation
KW - Genotype
KW - Hereditary hemorrhagic telangiectasia
KW - Intracranial hemorrhage
UR - http://www.scopus.com/inward/record.url?scp=84867793428&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.35622
DO - 10.1002/ajmg.a.35622
M3 - Article
C2 - 22991266
AN - SCOPUS:84867793428
SN - 1552-4825
VL - 158 A
SP - 2829
EP - 2834
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 11
ER -