Multicancer hereditary syndrome testing: Genetic counselors’ perspectives.

106 Background: The accessibility of cancer hereditary syndrome testing has increased, and the cost has declined significantly in the past few years. We conducted a national, quantitative survey of genetic counselors (GCs) to assess their perspectives on what influences hereditary cancer genetic testing decisions and practices, with a focus on cost. This survey was funded by NIH, conducted by UCSF TRANSPERS, and supported by the National Society of Genetic Counselors(NSGC). Methods: The survey was developed through literature review, expert interviews, and a pilot. Sent to the NSGC Cancer Special Interest Group via email. Chi-square tests were used to examine variability. Results: The survey response rate was 56% (202/363). Multiple hereditary cancer syndrome tests are discussed often/always by 86% of genetic counselors (GCs).The existence of an institutional protocol on multiple hereditary cancer syndrome testing was reported by 35.4% of GCs. When asked about GC counseling encounters, GCs report insurance rarely/never pays for: 25.2% pre-test in-person,39.7% for pre-test tele-genetics, 35.4% post-test in-person, and 52.9% post-test tele-genetics. GCs rated clinical factors higher than cost as influencing decision for multiple hereditary syndrome cancer testing (table); the total cost of the test was least important. These patterns were similar across the GCs institution types and years in practice. Conclusions: We found consistent use of multiple hereditary cancer syndrome tests, with less focus on cost, out-of-pocket, and insurance coverage and more of a focus on clinical indicators. GCs reported challenges with reimbursement for GC counseling encounters. The shift toward more genetic counseling encounters via tele-genetics necessitates evaluation of insurance reimbursement.[Table: see text]

Multicancer hereditary syndrome testing: Genetic counselors’ perspectives.

10594 Background: The accessibility of cancer hereditary syndrome testing has increased, and the cost has declined significantly in the past few years. We conducted a national, quantitative survey of genetic counselors (GCs) to assess their perspectives on what influences hereditary cancer genetic testing decisions and practices, with a focus on cost. This survey was funded by NIH, conducted by UCSF TRANSPERS, and supported by the National Society of Genetic Counselors (NSGC). Methods: The survey was developed through literature review, expert interviews, and a pilot. Sent to the NSGC Cancer Special Interest Group via email. Chi-square tests were used to examine variability. Results: The survey response rate was 56% (202/363). Multiple hereditary cancer syndrome tests are discussed often/always by 86% of genetic counselors (GCs). The existence of an institutional protocol on multiple hereditary cancer syndrome testing was reported by 35.4% of GCs. When asked about GC counseling encounters, GCs report insurance rarely/never pays for: 25.2% pre-test in-person, 39.7% for pre-test tele-genetics, 35.4% post-test in-person, and 52.9% post-test tele-genetics. GCs rated clinical factors higher than cost as influencing decision for multiple hereditary syndrome cancer testing (table); the total cost of the test was least important. These patterns were similar across the GCs institution types and years in practice. Conclusions: We found consistent use of multiple hereditary cancer syndrome tests, with less focus on cost, out-of-pocket, and insurance coverage and more of a focus on clinical indicators. GCs reported challenges with reimbursement for GC counseling encounters. The shift toward more genetic counseling encounters via tele-genetics necessitates evaluation of insurance reimbursement.[Table: see text]

A rare mutation of thyroid hormone receptor beta gene in thyroid hormone resistance syndrome

Summary Resistance to thyroid hormone (RTH) is a rare hereditary syndrome with impaired sensitivity to thyroid hormones (TH) and reduced intracellular action of triiodothyronine (T3) caused by genetic variants of TH receptor beta (TRB) or alpha (TRA). RTH type beta (RTHβ) due to dominant negative variants in the TRB gene usually occurs with persistent elevation of circulating free TH, non-suppressed serum TSH levels responding to a thyrotropin-releasing hormone (TRH) test, an absence of typical symptoms of hyperthyroidism and goiter. Here, we present a rare variant in the TRB gene reported for the first time in an Italian patient with generalized RTHβ syndrome. The patient showed elevated TH, with non-suppressed TSH levels and underwent thyroid surgery two different times for multinodular goiter. The genetic test showed a heterozygous mutation in exon 9 of the TRB gene resulting in the replacement of threonine (ACG) with methionine (ATG) at codon 310 (p.M310T). RTHβ syndrome should be considered in patients with elevated TH, non-suppressed TSH levels and goiter. Learning points Resistance to thyroid hormone (RTH) is a rare autosomal dominant hereditary syndrome with impaired tissue responsiveness to thyroid hormones (TH). Diagnosis of RTH is usually based on the clinical finding of discrepant thyroid function tests and confirmed by a genetic test. RTH is a rare condition that must be considered for the management of patients with goiter, elevation of TH and non-suppressed serum TSH levels in order to avoid unnecessary treatments.

Genetic Counseling for Hereditary Gastric and Pancreatic Cancer in High-Risk Gastrointestinal Cancer Clinics: An Effective Strategy

The identification of high-risk groups of gastric (GC) and pancreatic adenocarcinoma (PC) due to a hereditary basis could imply a benefit in the affected families by establishing personalized preventive strategies. We aimed at assessing the diagnostic yield of GC/PC hereditary syndromes in individuals evaluated based on specific clinical criteria. In total, 77 unrelated individuals (45 from GC group/32 from PC group) were recruited: 51 (66.2%) cancer diagnosis ≤60 years, 3 (4%) with personal history of GC/PC and other cancer and 23 (29.8%) due to family history. Immunohistochemical analysis of DNA mismatch repair proteins was performed in 38 (49.3%) available tumors, being pathological in one (2%) GC. A genetic analysis was performed if clinical criteria of hereditary syndrome were fulfilled, identifying a mutation in 10/22 (45.5%) families [7/16 (43.7%) with GC and 3/6 (50%) with PC] and 19 (24.7%) fulfilled criteria of familial cancer. Diagnosis of cancer <40 years and personal history of other cancers were independent risk factors of a hereditary syndrome [OR:11.3 (95%IC 1.9–67); p = 0.007 and OR:17.4 (95% IC 2.5–119.9); p = 0.004; respectively]. The selection of patients based on clinical criteria leads to high diagnostic yield, detecting a causative germline mutation in almost half of the cases; therefore, both meticulous genetic counseling and use of multi-gen panels is crucial.

DIAGNOSTIC DIFFICULTIES IN MutYH-ASSOCIATED POLYPOSIS (case report)

MutYH-associated polyposis (MAP) is hereditary syndrome with autosomal recessive inheritance, caused by biallelic mutation in MutYH gene and characterized by presence of multiple (20 and more) polyps in the bowel and increased life-time risk of colorectal cancer. At the same time finding 2 heterozygous mutations in MutYH gene (by Sanger method) doesn`t mean the diagnosis of MAP because of need to confirm their biallelic location. This case-report demonstrates difficulties in diagnostic of MAP caused by inability to investigate parent DNA samples and our options for solution of this problem.

Genetic counseling to outpatient cancer population.

e13009 Background: Recent advances in genetics and molecular biology have made possible to define the hereditary risk of certain diseases. About 10% of cancer are due to a hereditary syndrome and increasing access to genetic testing allows us to identify people or families at risk. Methods: A multidisciplinary team composed of clinical oncologists and geneticists retrospectively evaluated all cancer patients referred to the outpatient clinics of the Hospital de Clínicas de Porto Alegre Cancer Center between October 1st, 2014 and July 31st, 2015. Epidemiological data, pathological examination and family history of cancer recorded in the electronic database at the first visit to the oncologist were analyzed. Results: A total of 708 patients were analyzed. 44 (6.21%) patients were identified and referred for genetic evaluation by the clinical oncologist. Another 85 (12.0%) patients were identified by the multidisciplinary team, completing a total of 129 (18.22%), patients that should be evaluated to the presence of a hereditary syndrome. 164 (23.16%) patients could not be evaluated by the multidisciplinary team because insufficient data were recorded especially those related to family history of cancer. The main diagnosis that indicated genetic evaluation were colorectal cancer (47 cases - 36.43%), breast cancer (36 cases - 27.90%) and ovarian cancer (8 cases - 6.20%). Conclusions: A multidisciplinary evaluation of the oncologic patient is mandatory. Few patients are referred to a genetic counseling and 1 out of 4 patient could not be evaluated because there was missing data in the medical records. A precise genetic evaluation can identify patient / families at risk to develop cancer, allowing the development of cancer prevention strategies in this high-risk population.

Scaphoid Fracture in a Patient with a Scaphotrapezial Synostosis: A Case Report and Literature Review

Introduction. Scaphotrapezial synostosis has been rarely reported in the literature and only one case underwent surgical treatment for scaphoid fracture. Presentation of Case. A 15-year-old male presented with a painful left wrist following a fall. The initial radiographs showed a displaced scaphoid proximal pole fracture and a Scaphotrapezial synostosis. The fracture was then fixed percutaneously with satisfactory outcome. Discussion. Scaphotrapezial synostoses are very rare and most found in patients with multiple congenital anomalies or as part of a hereditary syndrome. They have previously been reported; however, we found only one case reporting a concomitant scaphoid fracture. Conclusion. This is the second case of its kind to report surgical treatment of scaphoid fracture associated with a congenital Scaphotrapezial synostosis.