Clinical Features of Patients with Hereditary Angioedema with Normal C1 Inhibitor: A Study of Seventy-Four Brazilian Individuals Belonging to Nine Unrelated Families

RationaleHereditary angioedema (HAE) is an autosomal dominant disorder, characterized by episodes of swelling of face, extremities and larynx, and attacks of abdominal pain. The majority of patients with HAE present mutations in the gene coding for C1 inhibitor (C1-INH); in addition, mutations in the gene coding for coagulation factor XII (FXII) have been described in patients with normal C1-INH (HAE-FXII). Our aim was to analyze clinical features of Brazilian patients with HAE-FXII.MethodsSeventy-four individuals from 9 unrelated families were studied. Index cases presented clinical features of HAE-FXII. Mutations were detected by allelic discrimination and sequencing of exon 9 of F12 gene. All patients and relatives completed a questionnaire assessing clinical characteristics and severity of disease.ResultsMissense mutation c.983C>A(p.Thr328Lys) in F12 gene was identified in 46 subjects (31 female,15 male). Twenty-nine subjects (22 female,7 male) presented symptoms of HAE, including 16 with severe (all female), 6 moderate (2 female, 4 male) and 7 mild (2 female, 5 male) symptoms. Abdominal attacks were predominant (69%), followed by swelling of face (62%), limbs (59%), upper respiratory tract (24%), and genitals (14%). Seventeen were asymptomatic (9/31 female, 8/15 male). Mean age at onset of symptoms was 20 years, and maternal to paternal transmission of c.983C>A mutation was 1.25:1.ConclusionsOur HAE-FXII patients were mainly women, presenting more severe symptoms than men. Predominant symptoms were abdominal pain, and swelling of face and limbs. Age at onset of symptoms was in keeping with reports from other areas of the world. Maternal transmission of mutation was slightly higher than paternal transmission. RationaleHereditary angioedema (HAE) is an autosomal dominant disorder, characterized by episodes of swelling of face, extremities and larynx, and attacks of abdominal pain. The majority of patients with HAE present mutations in the gene coding for C1 inhibitor (C1-INH); in addition, mutations in the gene coding for coagulation factor XII (FXII) have been described in patients with normal C1-INH (HAE-FXII). Our aim was to analyze clinical features of Brazilian patients with HAE-FXII. Hereditary angioedema (HAE) is an autosomal dominant disorder, characterized by episodes of swelling of face, extremities and larynx, and attacks of abdominal pain. The majority of patients with HAE present mutations in the gene coding for C1 inhibitor (C1-INH); in addition, mutations in the gene coding for coagulation factor XII (FXII) have been described in patients with normal C1-INH (HAE-FXII). Our aim was to analyze clinical features of Brazilian patients with HAE-FXII. MethodsSeventy-four individuals from 9 unrelated families were studied. Index cases presented clinical features of HAE-FXII. Mutations were detected by allelic discrimination and sequencing of exon 9 of F12 gene. All patients and relatives completed a questionnaire assessing clinical characteristics and severity of disease. Seventy-four individuals from 9 unrelated families were studied. Index cases presented clinical features of HAE-FXII. Mutations were detected by allelic discrimination and sequencing of exon 9 of F12 gene. All patients and relatives completed a questionnaire assessing clinical characteristics and severity of disease. ResultsMissense mutation c.983C>A(p.Thr328Lys) in F12 gene was identified in 46 subjects (31 female,15 male). Twenty-nine subjects (22 female,7 male) presented symptoms of HAE, including 16 with severe (all female), 6 moderate (2 female, 4 male) and 7 mild (2 female, 5 male) symptoms. Abdominal attacks were predominant (69%), followed by swelling of face (62%), limbs (59%), upper respiratory tract (24%), and genitals (14%). Seventeen were asymptomatic (9/31 female, 8/15 male). Mean age at onset of symptoms was 20 years, and maternal to paternal transmission of c.983C>A mutation was 1.25:1. Missense mutation c.983C>A(p.Thr328Lys) in F12 gene was identified in 46 subjects (31 female,15 male). Twenty-nine subjects (22 female,7 male) presented symptoms of HAE, including 16 with severe (all female), 6 moderate (2 female, 4 male) and 7 mild (2 female, 5 male) symptoms. Abdominal attacks were predominant (69%), followed by swelling of face (62%), limbs (59%), upper respiratory tract (24%), and genitals (14%). Seventeen were asymptomatic (9/31 female, 8/15 male). Mean age at onset of symptoms was 20 years, and maternal to paternal transmission of c.983C>A mutation was 1.25:1. ConclusionsOur HAE-FXII patients were mainly women, presenting more severe symptoms than men. Predominant symptoms were abdominal pain, and swelling of face and limbs. Age at onset of symptoms was in keeping with reports from other areas of the world. Maternal transmission of mutation was slightly higher than paternal transmission. Our HAE-FXII patients were mainly women, presenting more severe symptoms than men. Predominant symptoms were abdominal pain, and swelling of face and limbs. Age at onset of symptoms was in keeping with reports from other areas of the world. Maternal transmission of mutation was slightly higher than paternal transmission.