Preimplantation Genetic Testing of Multiple Endocrine Neoplasia Type 2A

Abstract

Background: When discussing matters of reproduction, the 2015 revised guidelines for the management of medullary thyroid carcinoma recommend that patients diagnosed with multiple endocrine neoplasia type 2A (MEN 2A) are informed about the option of Preimplantation Genetic Testing for Monogenic Disorders (PGT-M). In addition, patients seem to have a genuine interest in reproductive options. However, there are just two reports worldwide of this technology being used for patients with MEN 2A. We here present, in a Danish couple where the man has MEN 2A, the first European family with children born after PGT-M. Objective: To report the results of PGT-M in relation to multiple endocrine neoplasia type 2A with the aim to increase awareness among physicians treating this and other genetic disorders. Methods: A Danish couple was referred to the PGT Center at Copenhagen University Hospital Rigshospitalet and opted for PGT-M after counseling by a clinical geneticist and a fertility doctor. The embryos were diagnosed using microsatellite polymorphic marker close to RET. Results: The couple had two healthy children born in 2017 and 2019 as a result of a total of three ICSI treatments including controlled ovarian stimulation, oocyte retrieval and PGT-M, and a total of six blastocyst transfers. Conclusion: A session with a clinical geneticist covering all reproductive options for patients in early adult life is a relevant part of the clinical management of patients with MEN 2A, and other patients with hereditary cancer predisposition syndromes.

Understanding the variant landscape, and genetic epidemiology of Multiple Endocrine Neoplasia in India

“…Apart from early diagnosis and identification of asymptomatic carriers, genetic testing has also been shown to aid in preimplantation diagnosis 1,[49][50][51] , thereby offering yet another way of tackling MEN cancers preemptively and more effectively. Thus, genetic testing forms an integral part of several stages of the MEN clinical process, and through our work we have aimed to facilitate it.…”

Preimplantation genetic testing for embryos predisposed to hereditary cancer: Possibilities and challenges

“…The likelihood of transmission of the genetic pathogenic variant responsible for cancer from parents to their offspring varies between diseases. For individuals who carry the MEN2A gene pathogenic variant, the probability of transmitting the pathogenic rearranged during transfection (RET) variant to their offspring is 50%, 11 and the same probability is observed for individuals who carry germline retinoblastoma 1 ( RB1 ) gene pathogenic variants responsible for the development of hereditary RB . 7 In RB, 45–50% of patients who develop the disease by the germline pathogenic variant are capable of transmitting the disease to their offspring, 12 although RB is also caused by non-inherited pathogenic variants (somatic carcinomas).…”

“… Name Inheritance cancer syndrome Mechanism of cancer Variant Name of the disease Reference MEN2 Autosomal dominant Germline pathogenic variants of the RET proto-oncogene C.1858T > C, P.C620R germline variant MTC, parathyroid tumors, and pheochromocytoma and Hirschsprung's disease Würgler et al. 11 MEN1 Autosomal dominant Associated with germline and somatic inactivating mutations in the MEN1 gene Chromosome 11q13, encodes the 610 amino acid protein menin Tumors in multiple endocrine tissues Lima et al. 13 HBOC Autosomal dominant BRCA2 ; BRCA1 gene pathogenic variant C.7436_7805del [GenBank U43746]); BRCA1 pathogenic variant carrier (5273G[A In exon 19) Breast cancer, ovarian cancer, pancreatic cancer, and prostate cancer Lee et al.…”

The diagnosis and management of pheochromocytoma and paraganglioma during pregnancy

“…It also follows that all female patients with a known hereditary PPGL syndrome should be carefully assessed for tumors using biochemical testing and cross-sectional imaging at the time of pregnancy planning [ 4 , 18 ]. Pre-implantation genetic diagnosis may also be relevant to discuss with women at this time [ 37 ].…”