Nager acrofacial dysostosis is a rare craniofacial syndrome characterized by facial anomalies (cleft palate, external ear abnormalities, and micrognathia) and limb defects due to haploinsufficiency of SF3B4 (or SAP49), a protein involved in pre-mRNA splicing. We describe a 31-year-old female patient with Nager syndrome who presented to our institution with synchronous, bilateral breast cancer. She was treated with neoadjuvant hormonal therapy, bilateral mastectomies, and adjuvant chemotherapy with dose-dense doxorubicin, cyclophosphamide, and paclitaxel (ddAC-T). No other germline mutations were identified in a 29-gene panel of known breast cancer-associated genes. To our knowledge, this is the first report of cancer in a patient with Nager syndrome. Somatic inactivating mutations of SF3B4 occur occasionally in breast cancer, and these findings support the idea that SF3B4 is a tumor suppressor. This study illustrates the importance of evaluating the risk of chronic disease in individuals with rare inherited disorders.
Keywords: SAP49; SF3B4; Spliceosome; Splicing; c.1060dupC.