RESUMO
MUTYH -associated polyposis (MAP) is an autosomal recessive disorder where the inheritance of constitutional biallelic pathogenic MUTYH variants predisposes a person to the development of adenomas and colorectal cancer (CRC). It is also associated with extracolonic and extraintestinal manifestations that may overlap with the phenotype of familial adenomatous polyposis (FAP). Currently, there are discrepancies in the literature regarding whether certain phenotypes are truly associated with MAP. This narrative review aims to explore the phenotypic spectrum of MAP to better characterise the MAP phenotype. A literature search was conducted to identify articles reporting on MAP-specific phenotypes. Clinical data from 2109 MAP patients identified from the literature showed that 1123 patients (53.2%) had CRC. Some patients with CRC had no associated adenomas, suggesting that adenomas are not an obligatory component of MAP. Carriers of the two missense founder variants, and possibly truncating variants, had an increased cancer risk when compared to those who carry other pathogenic variants. It has been suggested that somatic G:C>T:A transversions are a mutational signature of MAP, and could be used as a biomarker in screening and identifying patients with atypical MAP, or in associating certain phenotypes with MAP. The extracolonic and extraintestinal manifestations that have been associated with MAP include duodenal adenomas, duodenal cancer, fundic gland polyps, gastric cancer, ovarian cancer, bladder cancer and skin cancer. The association of breast cancer and endometrial cancer with MAP remains disputed. Desmoids and Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPEs) are rarely reported in MAP, but have long been seen in FAP patients, and thus could act as a distinguishing feature between the two. This collection of MAP phenotypes will assist in the assessment of pathogenic MUTYH variants using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) Variant Interpretation Guidelines, and ultimately improve patient care.
RESUMO
Increasing demand for clinical genetic services may impact the resources and quality of genetic counseling, potentially impacting patient outcomes. Using a psychosocial screening tool may aid the provision of genetic counseling by reliably identifying patients' psychosocial needs. The Genetic Psychosocial Risk Instrument (GPRI) is a validated genetic-specific screening tool designed to identify psychological risk factors that predict distress in patients having genetic testing. This questionnaire-based study investigated the perceived acceptability, feasibility, and usefulness of the GPRI in patients and clinicians in routine clinical genetic practice. From December 2018 to January 2019, 154 patients attending an Australian clinical genetic service were invited to complete a paper-based survey that included the GPRI. The GPRI was scored and provided to the clinician for use in the appointment. In February 2019, clinicians completed an anonymous online survey regarding acceptability, feasibility, and usefulness of the GPRI. Descriptive statistics, chi-squared, t tests, and regression analyses were used to analyze the patient data, and descriptive statistics were employed for clinician surveys. A total of 145 patients participated (94% response rate). The average GPRI score was 46.3 (95% CI 43.6-49.0) with 41% of patients meeting the 50-point threshold indicating high risk for psychological distress. The GPRI was highly acceptable to patients, regardless of their level of psychosocial risk. Fourteen clinicians participated (54% response rate): 85% found the GPRI not too time consuming, and 86% believed it improved patient care by identifying patient needs. All were willing to use the GPRI routinely. The use of the GPRI is highly acceptable to patients and clinicians in this setting, assisting in identifying patients at risk for distress, prompting clinicians to address concerns, provide psychosocial support, and consider ongoing referral. As 41% of patients' scores indicated a high risk of distress, the GPRI is an important tool for potentially enhancing overall patient outcomes.