Angioedema hereditary 7 D81.4

Hereditary angioedema-7, also called hereditary angioedema type VII, or HAE7 for short, is a very rare autosomal dominant inherited disorder caused by a heterozygous mutation in the MYOF gene (604603) on chromosome 10q24.

The disorder is due to abnormal vascular permeability (Ariano et al. 2020). In three affected female members of the Italian family with HAE7 described by Ariano et al. (2020), Ariano et al. identified a heterozygous missense mutation in the MYOF gene (R217S; 604603.0001). An unaffected female family member also carried the mutation, suggesting incomplete penetrance. In vitro functional expression studies in HEK293 cells showed that the mutant protein was localized mainly to the plasma membrane and exhibited more intense colocalization with VEGFR2 (191306) than observed in wild-type MYOF. It is hypothesized that increased expression of VEGFR2 at the endothelial cell membrane could cause enhanced VEGF-mediated intracellular signaling, which could lead to vascular leakage.

The clinical picture is characterized by recurrent, episodic swelling of the face, lips and oral mucosa. The first clinical signs of anigoedema appear in the second decade of life.

Ariano et al (2020) reported on an Italian family in which a mother and her two daughters suffered from HAE. The patients developed recurrent angioedema without urticaria in the second decade of life. Symptoms included swelling of the face, lips, and oral mucosa. The mother had a single attack involving the upper respiratory tract. Attacks started slowly and subsided slowly. Menstruation and warm outdoor temperatures were identified as precipitating factors. Nail fold capillaroscopy showed tortuous loops, microbleeds, and decreased skin transparency due to edema.

1. Ariano A et al. (2020) A myoferlin gain-of-function variant associates with a new type of hereditary angioedema. (Letter) Allergy 75: 2989-2992.
2. Santacroce R et al (2021) The genetics of hereditary angioedema: A review. J Clin Med 10: 2023.
3. Veronez CL et al (2021) The Expanding Spectrum of Mutations in Hereditary Angioedema. J Allergy Clin Immunol Pract 9: 2229-2234.