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Betegségjelentés · Immunological

Hereditary Angioedema

Whole genome sequencing identifies all hereditary angioedema molecular subtypes: SERPING1 variants (types 1 and 2), F12 variants (type 3), and ANGPT1/PLG variants, enabling selection among three distinct approved treatment mechanisms.

A betegségjelentés olyan ritka variánsokat keres, amelyekről ismert, hogy okozzák az általa lefedett betegségeket.

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A(z) condition ismertetése

A rare genetic disorder characterized by recurrent, unpredictable episodes of severe swelling that can affect the skin, upper respiratory tract, and gastrointestinal tract, resulting from a deficiency or dysfunction of C1 esterase inhibitor protein.

Hereditary angioedema (HAE) is a potentially life-threatening genetic condition characterized by recurrent episodes of subcutaneous and submucosal edema, most commonly affecting the extremities, face, gastrointestinal tract, and larynx. HAE affects approximately 1 in 50,000 individuals worldwide, with autosomal dominant inheritance and uniform penetrance but highly variable expressivity. Laryngeal attacks are the most feared complication; untreated, HAE carries a historical mortality rate of approximately 30% from upper airway obstruction. With modern on-demand and prophylactic therapies, mortality can be effectively eliminated when the diagnosis is established.

HAE is genetically heterogeneous. The most common forms, HAE types 1 and 2, are caused by SERPING1 pathogenic variants encoding C1 inhibitor. Type 1 (~85%) involves reduced C1-INH quantity; type 2 (~15%) involves normal or elevated quantity but dysfunctional protein. Both types are diagnosed by measuring C1-INH level and functional activity, together with reduced C4 complement levels. HAE type 3 (HAE with normal C1-INH), primarily affecting women and often triggered or worsened by estrogen, is caused by pathogenic variants in F12 (factor XII) in approximately 25% of cases; other cases have variants in ANGPT1 (angiopoietin-1), PLG (plasminogen), KNG1, or MYOF, with the remainder genetically unresolved. HAE type 3 characteristically has normal complement studies, making its diagnosis entirely gene-dependent.

The treatment landscape for HAE has been transformed by multiple mechanism-specific approved therapies: C1 inhibitor concentrate replacement (HAEGARDA, Berinert, Ruconest), plasma kallikrein inhibitor (lanadelumab for prophylaxis, subcutaneous icatibant for on-demand), bradykinin receptor antagonist (icatibant), and most recently garadacumab and donidalorsen. Treatment selection and dosing may be influenced by molecular subtype; for example, HAE type 3 patients often have different trigger profiles and hormonal sensitivity that inform management. All approved therapies provide protection regardless of SERPING1 vs F12 genotype, but the emerging precision medicine landscape increasingly rewards precise molecular diagnosis.

HAE with normal C1-INH (type 3) has normal complement studies and is invisible to standard biochemical HAE testing. Only molecular genotyping can confirm the diagnosis in this subtype, and a confirmed F12, ANGPT1, or PLG variant guides management and enables family cascade testing.

A vizsgált 2 betegség

Hereditary Angioedema

Autoszomális domináns

Hereditary angioedema (HAE) is a genetic disease characterized by the occurrence of transitory and recurrent subcutaneous and/or submucosal edemas resulting in swelling and/or abdominal pain.

Mit változtat a diagnózis

On-demand therapy: C1-INH concentrate, icatibant (B2 receptor antagonist), or ecallantide; prophylaxis: lanadelumab, garadacumab, C1-INH concentrate; avoidance of estrogen-containing medications in type 3

Vizsgált gének

Más néven

deficiency of C1 esterase inhibitor; familial angioneurotic edema; familial angioneurotic oedema; HAE; hereditary angioneurotic edema; hereditary angioneurotic oedema; hereditary bradykinine-induced angioedema; hereditary non histamine-induced angioedema

12 kapcsolódó altípust tartalmaz ↓
  • angioedema, hereditary, 4
  • angioedema, hereditary, 5
  • angioedema, hereditary, 6
  • angioedema, hereditary, 7
  • angioedema, hereditary, 8
  • hereditary angioedema type 1
  • hereditary angioedema type 2
  • hereditary angioedema type 3
  • hereditary angioedema with C1Inh deficiency
  • hereditary angioedema with normal C1Inh
  • hereditary angioedema with normal C1inh not related to F12 or PLG variant
  • PLG-related hereditary angioedema with normal C1inh
MONDO:0019623Orphanet 91378MedGen 9229

Miért a teljes genom szekvenálás

HAE type 3 with normal C1-INH has normal complement studies and is undetectable by standard biochemical testing. Molecular diagnosis is the only path to confirmation, and whole genome sequencing evaluates all known HAE genes in one test.

HAE type 3 is completely missed by standard complement testing: only gene sequencing can confirm it

Standard HAE diagnosis relies on biochemical measurements: C1-INH antigenic level, C1-INH functional activity, and C4. These tests reliably identify HAE types 1 and 2, both caused by SERPING1 variants with C1-INH deficiency. However, HAE type 3, which may affect as many as 1 in 100,000 women, has entirely normal C4, C1-INH level, and C1-INH function. Women with recurrent unexplained angioedema, normal complement studies, and symptoms that worsen with oral contraceptives, pregnancy, or HRT may have HAE type 3 and remain undiagnosed for years. Molecular testing of F12, ANGPT1, and PLG is the only path to confirming this diagnosis.

Knowing the precise SERPING1 variant enables family cascade testing and stratifies novel therapy eligibility

Emerging HAE therapies, including RNA interference approaches targeting plasma kallikrein, have been developed with mechanism specificity that may translate into differential response by HAE subtype. SERPING1 variant type (missense, null, splicing) is associated with HAE type 1 vs type 2 classification, which informs interpretation of C1-INH functional assays. Family cascade testing, identifying at-risk relatives before a first laryngeal attack, prevents deaths and requires knowing the precise familial variant. Whole genome sequencing provides the complete SERPING1 coding and intronic sequence, detecting all variant types including large deletions that account for approximately 10-20% of SERPING1 pathogenic variants.

További immunological conditions

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Egy teszt. Egy életen át tartó válaszok.

Egy csomag, házhoz szállítva. Az egész genomját a diagnosztikai döntésekhez használt klinikai színvonalon szekvenáljuk. Orvos számára is használható jelentéseit 6–8 héten belül küldjük el a Genome Manager-be. Ezek tartósan érvényesek, és a tudomány fejlődésével frissülnek.

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Ingyenes szállítás · Eredmények 6–8 hét alatt

Kérem a Genome Testemet