Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)

APECED is inherited in an autosomal recessive manner. Both parents of an affected individual typically carry one pathogenic AIRE variant each and are unaffected. With each pregnancy, the recurrence risk for siblings is 25%. Prenatal molecular testing is technically possible once the familial pathogenic variants have been identified.

Diagnosis rests on any two of the three classic manifestations (chronic mucocutaneous candidiasis, , and Addison disease) and meeting these criteria establishes the diagnosis. Biallelic pathogenic AIRE variants confirm the diagnosis irrespective of clinical findings.

• Establishing the diagnosis through molecular confirmation resolves diagnostic uncertainty and supports appropriate clinical care.
• A confirmed molecular diagnosis enables specific and individualised surveillance of endocrine, mucocutaneous, and oncological manifestations and is a prerequisite for targeted medical care decided by the treating physicians in consultation with the affected individual.
• Identification of the familial pathogenic variants enables predictive and carrier testing in at-risk relatives and supports reproductive counselling.

• Garelli S, Dalla Costa M, Sabbadin C, Barollo S, Rubin B, Scarpa R, et al. Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients. J Endocrinol Invest. 2021;44(11):2493-510. doi:10.1007/s40618-021-01585-6. PMID:; PMCID: PMC8502131.
• Brenchley L, Ferré EMN, Schmitt MM, Gardner PJ, Lionakis MS, Moutsopoulos NM. Case report: dental findings can aid in early diagnosis of APECED syndrome. Front Dent Med. 2021;2:670624. doi:10.3389/fdmed.2021.670624. PMID:; PMCID: PMC10751037.
• Tarle M, Raguž M, Lukšić I. Head and neck malignancies in autoimmune polyendocrine syndrome type 1 (APS-1/APECED): a scoping review of molecular pathogenesis, clinical features, and outcomes. Int J Mol Sci. 2025;26(18):8969. doi:10.3390/ijms26188969. PMID:; PMCID: PMC12469869.
• Paparella R, Menghi M, Micangeli G, Leonardi L, Profeta G, Tarani F, et al. Autoimmune polyendocrine syndromes in the pediatric age. Children (Basel). 2023;10(3):588. doi:10.3390/children10030588. PMID:; PMCID: PMC10047132.