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Hereditary angioneurotic edema(HAE)

MedGen UID:
9229
Concept ID:
C0019243
Disease or Syndrome
Synonyms: ANGIOEDEMA, HEREDITARY, TYPE I; Angioedemas, Hereditary; C1 ESTERASE INHIBITOR DEFICIENCY; HAE; Hereditary Angioedema
SNOMED CT: HANE - Hereditary angioneurotic edema (82966003); HAE - Hereditary angioedema (82966003); Hereditary angioneurotic edema (82966003); Hereditary Quincke's edema (82966003); Hereditary angioedema (82966003)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Related genes: F12, SERPING1
 
Monarch Initiative: MONDO:0019623
OMIM® Phenotypic series: PS106100
Orphanet: ORPHA91378

Definition

Hereditary angioedema-1 and -2 (HAE1 and HAE2) refer to disorders caused by mutation in the SERPING1 (C1HN) gene. The disorders are clinically indistinguishable: both are characterized by episodic local subcutaneous edema and submucosal edema involving the upper respiratory and gastrointestinal tracts. HAE1, representing 85% of patients, is characterized by serum levels of C1NH less than 35% of normal (Cicardi and Agostoni, 1996; Bowen et al., 2001). HAE2 is characterized by normal or even elevated C1NH levels, but the protein is nonfunctional. Genetic Heterogeneity of Hereditary Angioedema See also HAE3 (610618), caused by mutation in the F12 gene (610619) on chromosome 5q35; HAE4 (619360), caused by mutation in the PLG gene (173350) on chromosome 6q26; HAE5 (619361), caused by mutation in the ANGPT1 gene (601667) on chromosome 8q23; HAE6 (619363), caused by mutation in the KNG1 gene (612358) on chromosome 3q27; HAE7 (619366), caused by mutation in the myoferlin gene (MYOF; 604603) on chromosome 10q23; and HAE8 (619367), caused by mutation in the HS3ST6 gene (619210) on chromosome 16p13. See also 300145 for a discussion of angioedema induced by ACE inhibitors. Zuraw (2008), Bork et al. (2020), and Veronez et al. (2021) provided detailed reviews of the clinical features, management, and pathogenesis of the different genetic forms of hereditary angioedema. The pathogenesis is complex and is related to excessive production of bradykinin, which causes dilation, as well as to other signaling pathways that regulate vascular permeability. [from OMIM]

Additional description

From MedlinePlus Genetics
Hereditary angioedema is a disorder characterized by recurrent episodes of severe swelling (angioedema). The parts of the body that are most often affected by swelling are the limbs, face, intestinal tract, and airway. Minor trauma or stress may trigger an attack, but swelling often occurs without a known trigger. Episodes involving the intestinal tract cause severe abdominal pain, nausea, and vomiting. Swelling in the airway can restrict breathing and lead to life-threatening obstruction of the airway. About one-third of people with this condition develop a non-itchy rash called erythema marginatum during an attack.

Symptoms of hereditary angioedema typically begin in childhood and worsen during puberty.  On average, untreated individuals have swelling episodes every 1 to 2 weeks, and most episodes last for about 3 to 4 days. The frequency and duration of attacks vary greatly among people with hereditary angioedema, even among people in the same family.

Hereditary angioedema is broadly divided into two types, which are distinguished by levels of a protein called C1 inhibitor (C1-INH) in the blood. These types are known as hereditary angioedema due to C1-INH deficiency and hereditary angioedema with normal C1-INH. 

Hereditary angioedema due to C1-INH deficiency is further divided into two types: type I occurs when C1-INH levels are low, and type II occurs when the C1-INH protein is not functioning correctly. 

The different types of hereditary angioedema have similar signs and symptoms. 

  https://medlineplus.gov/genetics/condition/hereditary-angioedema

Professional guidelines

PubMed

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Recent clinical studies

Etiology

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