RETRACTED ARTICLE: Multidisciplinary management for Peutz–Jeghers syndrome and prevention of vertical transmission to offspring using preimplantation genetic testing

Abstract

Background Peutz Jeghers syndrome (PJS) is an autosomal dominant genetic disorder caused by STK11 mutation with a predisposition to gastrointestinal polyposis and cancer. PJS patients suffer poor quality of life and are highly concerned about whether deleterious mutations transmit to their offspring. Therefore, this study aimed to propose feasible clinical management and provide effective preimplantation genetic testing for monogenic defect (PGT-M) strategies to protect offspring from inheriting the disease. Methods A hospital-based clinical retrospective analysis reviewing the clinical characteristics and fertility aspects was first conducted on 51 PJS patients at the First Affiliated Hospital of Zhengzhou University between January 2016 and March 2021. Among the 51 patients, the PGT-M strategy was further carried out in 4 couples, which started with a biopsy of the trophectoderm cells of embryos and whole genome amplification using multiple displacement amplification. Thereafter, single nucleotide polymorphism linkage analyses based on karyomapping were performed with copy number variations of the embryos identified simultaneously. Finally, prenatal diagnosis was used to verify the validity of the PGT-M results. Results A comprehensive management flowchart adopted by the multidisciplinary team model was formulated mainly focusing on clinical genetic and gastrointestinal aspects. Under the guidelines of this management, 32 embryos from 4 PJS pedigrees were diagnosed and 2 couples successfully conceived healthy babies free of the STK11 pathogenic mutation. Conclusions Our comprehensive management could help affected families avoid having children with PJS through preimplantation genetic testing and provide meaningful guidance for multidisciplinary clinical practice on PJS.

Peutz-Jeghers syndrome: revisited

“…This rare autosomal dominant entity is due to a mutation of serine-threonine kinase ( STK11/LKB1 ) gene on chromosome 19, and causes mucocutaneous pigmentation, hamartomatous polyps, digestive hemorrhage, intussusception, and malignancies. 1 - 9 These mutations have been detected in up to 70% of cases in affected families, and in 30% to 67% of sporadic cases. 4 Approximately 95% of the typical PJS pigmentations like small dark brown, circular or oval macules are distributed around the mouth, eyes, nostrils, and in the extremities.…”

“…4 , 5 PJS affects 1/50 000-20 000 people, and is associated with an increased risk of stomach, intestine, pancreas, breast, lung, uterus, ovaries, and testes cancers. 4 - 7 , 9 The incidence of cancers in PJS is almost 15 times higher than in general population. 7 The lifetime increased risk of malignancy by the age of 70 may be up to 90%.…”

“…4 , 6 Most common PJ gastrointestinal polyps are described in the small bowel (50%), stomach (36%), and colon (21%); extra-intestinal may be in the bladder, nostril, bronchi, or gallbladder. 3 , 4 , 6 , 7 , 9 Gastrointestinal polyps may cause bleeding, intussusception, and even rectal prolapse; 6 , 8 and the intussusception risk by age 10 is 15%, and by 20 years the risk is up to 50%. 7 Small bowel intussusception is the most urgent and life-threatening of all manifestations.…”

“…4 Suspected cases of PJS must have genetic testing and informed assent to have children; once an individual is diagnosed with PJS, all their at-risk relatives should be tested. 8 , 9 Patients with PJS must begin screening for polyps at the age of eight, with annual complete physical evaluations and blood exams, besides precocious tumor resections. 4 - 9 The prevention of surgical complications and monitoring of malignant transformation of the polyps include: control of total blood count, determination of CA-125 and CA-19-9 levels, imaging studies of digestive tract, testes, breast and pelvic organs.…”

“… 8 , 9 Patients with PJS must begin screening for polyps at the age of eight, with annual complete physical evaluations and blood exams, besides precocious tumor resections. 4 - 9 The prevention of surgical complications and monitoring of malignant transformation of the polyps include: control of total blood count, determination of CA-125 and CA-19-9 levels, imaging studies of digestive tract, testes, breast and pelvic organs. 4 - 9 Consensual guidelines for better managing patients with PJS are lacking.…”