Year: 2026
Type: conference-abstract
Abstract: Background: Hereditary angioedema (MIM#106,100) is a rare autosomal dominant disease characterized by recurrent cutaneous-submucosal edema.Heterozygous pathogenic variants in SERPING1 (MIM*606,860) coding for C1-esterase inhibitor (C1-INH) cause C1-INH-HAE (type 1-2).We reported four C1-INH-HAE cases in which the combination of clinically driven design process and genomic approaches disclosed the coexistence of two rare genetic diseases.Methods: Affected Patients were women in 75% of cases: a positive C1-INH-HAE family history occurred in 3 patients (66.7% type 1) while one case was sporadic (type 1).Patients were Caucasian and referred to the ITACA Reference Center in Rome (Policlinico Tor Vergata), Italy.In all of them, the genetic identification of a concurrent disease occurred after the C1-INH-HAE diagnosis.It was documented by clinically driven design processes in 75% (2 F, 1 M) of cases while in the sporadic case (1 F) it was an incidental finding.Three of the four documented diseases were rare neurological disorders.Case 1 (M) presented HAE symptoms onset in pediatric age: he inherited the SERPING1 pathogenic variant from his affected mother.The Patient presented progressive loss of coordination and balance and hypertrophic cardiomyopathy: autosomal recessive Friedreich Ataxia (MIM#229,300) was diagnosed in pediatric age (6 y.o.), due to a compound heterozygous GAA expansion in FXN gene.Case 2 (F) presented HAE symptoms in puberty: she inherited the SERPING1 pathogenic variant from her affected father.At stage II Tanner, she showed generalized acute epilepsy with drug-resistant myoclonic crisis: Myoclonic Epilepsy of Lafora 2 (MIM#620,681) was diagnosed due to compound heterozygous NHLRC1 pathogenic variants.Case 3 (F) was a sporadic C1-INH-HAE case in which molecular diagnosis was made at 55 y.o.She presented a very rare deletion of the whole SERPING1 gene and neuropathic symptoms compatible with the incidentally disclosed canonical PMP22 deletion causing Hereditary Neuropathy with liability to Pressure Palsies (HNPP, MIM#162,500).Case 4 (F) was born with congenital cardiopathy and mild dysmorphisms: Noonan Syndrome (MIM#163,950) was diagnosed, detecting a de novo PTPN11 pathogenic variant.At the same stage I Tanner, she also presented abdominal attacks: inherited SERPING1 pathogenic variant from her affected father was thus documented.Conclusions: We described the first Italian case series from C1-INH-HAE patients with SERPING1 pathogenic variants in whom genetic analyses detected the simultaneous presence of rare conditions that co-occurred in unrelated patients.Although rare, the possibility of being affected by two inherited genetic conditions should be suspected when clinical phenotypes are incoherent Page 2 of 26 Allergy, Asthma & Clinical Immunology (2026) 22:57with primary diagnoses.Consent to publish had been obtained.
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,090
OpenAlex ID: W7223059002