Abstract
CONTEXT: Carney complex (CNC) is a rare multiple neoplasia syndrome involving cardiac, endocrine, neural, and cutaneous tumors and a variety of pigmented skin lesions. CNC can be inherited as an autosomal dominant trait, but in about one-third of patients, the disease is caused by de novo mutation in the PRKAR1A gene localized on chromosome 17q22-24. Most of the mutations include single base substitutions and small deletions/insertions not exceeding 15 base pairs. Recently, large germline PRKAR1A deletions have been described and may cause a more severe phenotype. CASE DESCRIPTION: Herein, we report the cases of two siblings with CNC with a de novo large deletion of 107 kb at 17q24.2 associated with acromegaly in both and primary pigmented nodular adrenocortical disease, cardiac myxoma, and lethal metastatic melanotic schwannian tumor at the age of 27 years in one of them, supporting the hypothesis that large deletions of PRKAR1A lead to severe disease. CONCLUSIONS: To our knowledge, this is the first description of familial CNC in siblings in which neither parent carried the deletion in blood-derived DNA, suggesting that one of them had germ cell mosaicism for this deletion. Testing for large gene deletions should be obtained in all patients who meet the diagnostic criteria for CNC but do not have a PRKAR1A mutation by Sanger sequencing.