Utilization of Genetic Testing for RET Mutations in Patients with Medullary Thyroid Carcinoma: a Single-Center Experience.

Medullary thyroid carcinoma (MTC) is often due to the hereditary condition multiple endocrine neoplasia type 2 (MEN2) and it is standard of care to offer genetic testing to all diagnosed patients. This study used the Kaiser Permanente integrated medical record system to identify patients at risk for MEN2, assess adherence to clinical practice guidelines, and offer genetic counseling and testing. A query of the electronic medical records system identified patients with MTC. All patients with MTC who had not had RET gene testing, as well as patients who had positive RET gene testing, but had not yet had genetic counseling, were contacted and offered a genetics consultation. The query identified 142 patients with MTC. Fifty-six (40%) of those patients had not had the RET testing that all endocrine professional groups recommend. Forty-nine patients were eligible for the outreach, and, from this, 14 patients were scheduled for genetic counseling. Of the 94 individuals at our institution who had RET genetic testing, 25 (27%) were positive for a mutation. Of the 82 apparently sporadic cases, 13 (16%) carried a RET mutation. A family history of endocrine cancer and younger age at diagnosis significantly increased the risk carrying a RET mutation. However, approximately half of RET-positive patients did not have a significant family history of cancer and one-third were over age 50 at diagnosis. This study concludes that a significant proportion of patients with MTC are not receiving standard of care genetic testing and reinforces previous research that sporadic-appearing cases of MTC are often, in fact, hereditary.

A single visit multidisciplinary model for managing patients with mutations in moderate and high-risk genes in a community practice setting.

The introduction of screening for multiple high and moderate risk mutations in genes has resulted in a complex approach to patient care involving multiple disciplines. We sought to describe the feasibility of a single visit multidisciplinary approach to the management of patients with an identified high/moderate risk gene mutation. Patients who presented to our community hospital over a 1-year period who were found to have a high/moderate risk genetic mutation on a screening panel were referred to the High Risk Genetic Clinic. Thirty-five patients were included. The majority were female [34 (97.1%)], Hispanic [22 (62.9%)], with a family history of cancer [21 (60%)]. Mean age was 40.3 years. Most of the participants had a BRCA1 gene mutation [10 (28.6%)]. Patients were seen at the High Risk Genetic Clinic within a mean of 41.9 days from the day of genetic mutation diagnosis. Four patients did not show and were significantly younger (19.3 vs. 39.6 years, p = 0.014). In this community setting, we provided coordinated care within multiple disciplines related to a genetic mutation in a single clinic visit. Increased efforts at coordinating early care should be directed towards patients diagnosed at a younger age.

Optic Gliomas in Neurofibromatosis Type 1.

PURPOSE: To examine the incidence, presentation, and outcome of optic gliomas in children with neurofibromatosis type 1 (NF1) in Southern California Kaiser Permanente. METHODS: The authors queried the Southern California Kaiser Permanente electronic medical record database to find patients diagnosed as having NF1. Genetics, ophthalmology, and imaging medical records of patients with optic glioma were reviewed. RESULTS: A total of 708 patients younger than 21 years had a diagnosis of NF1 in Southern California Kaiser Permanente and 30 (4.2%) had a diagnosis of optic glioma. The average age of diagnosis was 5 years, with a range of 18 months to 12 years. Half (15 of 30) of the patients diagnosed as having optic glioma presented with symptoms (eg, vision loss, proptosis, and precocious puberty). Eight of 15 of the symptomatic patients were treated with surgery and/or chemotherapy. Symptomatic children were diagnosed later than those diagnosed through routine screening (5.7 vs 3.9 years old). The oldest child presented with symptoms at age 12 years. One asymptomatic patient had prophylactic chemotherapy. Sixty-three percent (19 of 30) of the gliomas were bilateral, 23% (7 of 30) were right-sided, and 13% (4 of 30) were left-sided. Fifty-three percent (17 of 30) of the gliomas involved the optic chiasm. CONCLUSIONS: Screening practices for optic glioma are inconsistent. Most children with NF1 at risk for optic glioma do not have even one visit with an ophthalmologist. Children with NF1 can develop asymptomatic optic glioma as early as age 1 year. Annual ophthalmologic examination and screening for precocious puberty in children with NF1 is important for early diagnosis of optic gliomas and may reduce morbidity. [J Pediatr Ophthalmol Strabismus. 2016;53(6):334-338.].

A systematic analysis of small supernumerary marker chromosomes using array CGH exposes unexpected complexity.

PURPOSE: A small supernumerary marker chromosome is often seen in patients with developmental disorders. Prior to array-based comparative genomic hybridization markers were rarely genotyped end to end. In this study, a valid genotype-to-phenotype correlation was possible because the supernumerary marker chromosomes were fully characterized by array-based comparative genomic hybridization in a genome-wide analysis. METHODS: Ten consecutive de novo small supernumerary marker chromosome cases were systematically genotyped using G-banding, C-banding, AgNOR staining, whole-genome array-based comparative genomic hybridization, and fluorescence in situ hybridization. RESULTS: Among 10 small supernumerary marker chromosome cases studied, 4 (40%) were not identified by array-based comparative genomic hybridization because of low-level mosaicism or because they lacked euchromatin. One case (10%) was a simple pericentromeric marker extending from 5p13.3 to 5q11.2. Five (50%) markers showed unexpected complexity. Two cases had markers that were derivative acrocentric (AgNOR+) chromosomes with the euchromatin from chromosomes 18p or 19p. Each of the other three cases with complex markers had unusual characteristics including a marker from noncontiguous segments of chromosome 19q, a highly complex rearrangement involving a chromosome 20 homolog as well as the small supernumerary marker chromosome, and a mosaic duplication of a proximal 8p marker. CONCLUSION: Small supernumerary marker chromosomes are frequently complex on the basis of our small sample. Whole-genome array-based comparative genomic hybridization characterization of the small supernumerary marker chromosome provided informed genetic counseling.