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FRI256 The Clinical Impacts Of Bi-allelic Germline Pathogenic Variant In TP53 In Two Patients With Li-Fraumeni Syndrome

Disclosure: V. Petry: None. D. Cohn: None. R.R. Oppenheimer: None. M.D. Estevez-Diz: None. A. Latronico: None. B.B. Mendonca: None. M.Q. Almeida: None. M.C. Fragoso: None. Background: Li-Fraumeni syndrome is an autosomal dominant cancer predisposition due to a heterozygous germline TP53 mutation. Th...

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Published in:Journal of the Endocrine Society 2023-10, Vol.7 (Supplement_1)
Main Authors: Petry, Vanessa, Cohn, Daniela, Oppenheimer, Romulo R V, Estevez-Diz, Maria D P, Latronico, Ana Claudia, Mendonca, Berenice Bilharinho, Almeida, Madson Q, Barisson Villares Fragoso, Maria Candida
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Language:English
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Summary:Disclosure: V. Petry: None. D. Cohn: None. R.R. Oppenheimer: None. M.D. Estevez-Diz: None. A. Latronico: None. B.B. Mendonca: None. M.Q. Almeida: None. M.C. Fragoso: None. Background: Li-Fraumeni syndrome is an autosomal dominant cancer predisposition due to a heterozygous germline TP53 mutation. This mutation is related to different types of cancer; mainly adrenocortical carcinomas (ACC), soft tissues and bone sarcomas, breast cancer, choroid plexus carcinoma and leukemias at early ages. Although little is known about the impact of this TP53 variant in the homozygous form. Methods: We described the clinical presentation and the follow-up of 2 patients with a TP53 (p.R337H) homozygous pathogenic variant inherited from their parents. Case 1: A two year old patient presented with a headache, vomiting and nuchal stiffness, and was taken to the ER where she had a CNS CT scan. The CT scan revealed a mass located at left intraventricular region She then had surgery to remove the tumor and the histological finding confirmed the diagnosis of choroid plexus carcinoma. She underwent adjuvant systemic chemotherapy Headstart III protocol. This was the first case of cancer within this family. The child was seen by a medical geneticist and a genetic test revealed a homozygous pathogenic variant (p.R337H) in TP53. Afterwards her parents were tested and both were heterozygous for the p.R337H mutation. The patient is now 4 years old and free of oncologic disease. Case 2: A 9 months old female patient presented with Cushing´s syndrome and heterosexual precocious puberty. The MRI revealed a right adrenal tumor and she underwent laparoscopic adrenalectomy. Oral hydrocortisone was initiated postoperatively as glucocorticoid replacement therapy and was gradually tapered off over 6 months. Both parents of the patient were heterozygous for the p.R337H mutation in TP53 and they reported several cases of cancer within the family. The patient inherited both mutated alleles TP53 p.R337H. She had normal puberty development and she reached the target height. The patient did not develop further neoplasms during long-term follow-up (23 years). Conclusions: We described 2 cases with a biallelic pathogenic variant in TP53 (p.R337H) who were diagnosed with cancer at early ages and who did not develop further neoplasms during the follow-up period. There is a previous case description in the literature of a patient with a homozygous p.R337H mutation in TP53 who developed ACC at an early age a
ISSN:2472-1972
2472-1972
DOI:10.1210/jendso/bvad114.251