D1.414 - The Clinical Course in a normal C1-Inhibitor Hereditary Angioedema family with Factor XII mutation

A 21-year-old lady presented with a massive lip swelling after an intense kiss with her boyfriend that occurred for the second time. Her medical history revealed that since the age of 17, she had experienced 3-4 times of mild one-day swelling of her left thumb without any urticaria. She did not consult a doctor about it. Subsequently, after her university exams, she developed facial swellings twice, each time lasting one day. But now, a month apart, she suffered two episodes of severe lip swelling after passionate kissing with her boyfriend. Each episode lasted about three days and did not subside any faster despite treatment with antihistamines and high-dose intravenous corticosteroids. She denied having abdominal pain or shortness of breath during these episodes. No one in her family had ever experienced swellings. The only medication she had been taking for the past two years was estrogen-containing contraceptives.

Her diagnostic workup included C1-INH-Ag and activity, C3, C4, CH-50, ANA, subsets, anti-ds-DNA, serum tryptase levels, total serum IgE, screening for specific IgE on common inhalation allergens, complete blood count, all resulting within normal range. Subsequently, genetic tests were carried out, first for the patient, then for all family members.

Genetic tests revealed a mutation in the F12 gene in our patient. Her brother (16 years old), her sister (14 years old), and her father, a 56-year-old man of Algerian origin, had the same mutation, but had not yet suffered from swellings. Her father and siblings were informed about medications that can trigger swelling attacks and instructed to avoid them in the future. The patient was informed about her attack triggers, received icatibant to treat acute attacks, and was trained in its application. Her contraceptive was changed to a progestin-only pill. She has been symptom-free ever since.

This family study, with an eight-year follow-up period, demonstrates i) the oligosymptomatic course of the HAE-F12 mutation in some patients, ii) the prevention of swelling attacks by discontinuing triggering medications, and suggests iii) a potentially higher number of undiagnosed HAE-F12 mutation patients. Had the patient not received estrogen-containing pill, the disease would likely have remained undetected in her family for a significantly longer period.