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Phosphatidylinositol Glycan Anchor Biosynthesis class H (PIGH) is an essential player in the glycosylphosphatidylinositol (GPI) synthesis, an anchor for numerous cell membrane‐bound proteins. PIGH deficiency is a newly described and rare disorder associated with developmental delay, seizures and behavioral difficulties. Herein, we report three new unrelated families with two different bi‐allelic PIGH variants, including one new variant p.(Arg163Trp) which seems associated with a more severe phenotype. The common clinical features in all affected individuals are developmental delay/intellectual disability and hypotonia. Variable clinical features include seizures, autism spectrum disorder, apraxia, severe language delay, dysarthria, feeding difficulties, facial dysmorphisms, microcephaly, strabismus, and musculoskeletal anomalies. The two siblings homozygous for the p.(Arg163Trp) variant have severe symptoms including profound psychomotor retardation, intractable seizures, multiple bone fractures, scoliosis, loss of independent ambulation, and delayed myelination on brain MRI. Serum iron levels were significantly elevated in one individual. All tested individuals with PIGH deficiency had normal alkaline phosphatase and CD16, a GPI‐anchored protein (GPI‐AP), was found to be decreased by 60% on granulocytes from one individual. This study expands the PIGH deficiency phenotype range toward the severe end of the spectrum with the identification of a novel pathogenic variant., GPIs are synthetized by the GPI‐GnT, comprising PIGH, on the cytoplasmic membrane of ER from a phosphatidylinositol and a N‐acetylglucosamine. Once flipped to the luminal side of the ER and further synthesized, GPIs are added to proteins to form GPI‐APs. GPI‐APs are transported to the cytoplasmic membrane via the Golgi. Features of individuals with bi‐allelic PIGH variants are presented according to their frequency.

Background: Contralateral prophylactic mastectomy (CPM) is a risk-reducing surgery offered to women with unilateral breast cancer intended to reduce the risk of contralateral breast cancer. The rate of CPM among women with unilateral early-stage breast cancer has risen in the United States over the past two decades, despite limited evidence for a survival benefit in the majority of patients. We evaluated sociodemographic and clinical factors, including receipt and results of BRCA1/2 genetic testing or multigene panel testing, associated with CPM among young women with unilateral early-stage breast cancer. Methods: We conducted a retrospective cohort study of women diagnosed with unilateral stage 0-III breast cancer at age ≤ 50 years between January 2007 and December 2017 at Columbia University Irving Medical Center (CUIMC) in New York, NY. Patients with bilateral breast cancer, male breast cancer, metastatic disease, or missing breast surgery information were excluded from the analysis. Demographics (age, race/ethnicity, marital status, primary health insurance) and clinical information (stage and year of diagnosis, family history of breast cancer) were collected from the electronic health record (EHR) and New York Presbyterian Hospital (NYPH) Tumor Registry. We also determined receipt of genetic testing (yes/no) and results (pathogenic/likely pathogenic [P/LP], variant of uncertain significance [VUS], negative). The primary outcome of interest was receipt of CPM. Multivariable logistic regression models were used to assess the association between demographic and clinical factors, including receipt and results of genetic testing, and CPM. Results: Among the 1207 women who met inclusion criteria, median age was 42.9 years (standard deviation [SD], 5.7 years), and 43% identified as non-Hispanic white, 27% Hispanic, 13% non-Hispanic black, 10% Asian, and 7% other. Nearly half (49.5%, N=597) underwent germline genetic testing for cancer susceptibility genes, and of those tested, 12.6% had P/LP variants (of which 69.3% were in BRCA1/2), 14.2% had VUSs, and 73.2% had negative results. Over one-quarter (27.7%, N = 334) underwent CPM, 29.8% had a unilateral mastectomy and 42.5% had lumpectomy. In multivariable analysis, women with a younger age at diagnosis, more advanced stage disease, and a family history of breast cancer were more likely to undergo CPM. There were no differences in CPM rates by primary health insurance. Asian women were less likely to undergo CPM compared to non-Hispanic white women (odds ratio [OR]=0.56, 95% confidence interval [CI]=0.34-0.95). Compared to women who did not undergo genetic testing, CPM rates were higher among those who had a P/LP variant (OR=5.12, 95% CI=2.94-8.89), those who had a VUS (OR=1.94, 95% CI=1.23-3.36) or negative results (OR=1.51, 95% CI=1.09-2.09). From 2007 to 2017, rates of genetic testing uptake in the study population increased from 17.9% to 67.1%, and CPM rates increased from 15.2% to 30.0%. Conclusions: Among young women with unilateral early-stage breast cancer, CPM rates were relatively high and increased over time. Women with P/LP variants were over 5 times more likely to undergo CPM compared to those who did not undergo genetic testing, however, even those with VUS or negative results were over 50% more likely to undergo CPM. The American Society of Breast Surgeons now recommends genetic testing for hereditary breast cancer among all women diagnosed with breast cancer. As multigene panel testing is increasingly utilized among women with breast cancer, further evaluation of its role in decisions regarding risk-reducing surgery such as CPM is warranted, particularly given the unclear implications of moderate-risk pathogenic variants and VUS results on contralateral breast cancer risk. Citation Format: Julia E McGuinness, Boya Guo, Meghna S Trivedi, Tarsha Jones, Wendy K Chung, Roshni Rao, Elana Levinson, Carrie Koval, Donna Russo, Ilana Chilton. Association between genetic testing for hereditary breast cancer and contralateral prophylactic mastectomy among young women diagnosed with early-stage breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-11.

Objective Growing use of clinical exome sequencing (CES) has led to an increased burden of genomic education. Self-guided educational tools can minimize the educational burden for genetic counselors (GCs). The effectiveness of these tools must be evaluated. Methods Parents of patients offered CES were randomized to watch educational videos before their visit or to receive routine care. Parents and GCs were surveyed about their experiences following the sessions. The responses of the video (n = 102) and no-video (n = 105) groups were compared. Results GCs reported no significant differences between parents in the video and no-video groups on genetics knowledge or CES knowledge. In contrast, parents’ scores on genetics knowledge questions were lower in the video than no-video group (p = 0.007). Most parents reported the videos were informative, and the groups did not differ in satisfaction with GCs or decisions to have CES. Conclusion GCs and parents perceived the videos to be beneficial. However, lower scores on genetics knowledge questions highlight the need for careful development of educational tools. Practice implications Educational tools should be developed and assessed for effectiveness with the input of all stakeholders before widespread implementation. Better measures of the effectiveness of these educational tools are needed.

Background Myositis Ossificans Cicumscripta is a rare condition characterized by aberrant bone formation in paramuscular soft tissue of the extremities usually associated with trauma or a genetic mutation. Very few cases involve the head or neck and it is rarely found in the pediatric population. Objectives We present a case of a 5-month old with a rapidly growing posterior neck mass suspicious for neoplasia, which was treated with surgical resection and found to be a non-traumatic, non-genetic form of Myositis Ossificans. The workup, treatment, and findings of the patient are outlined and a review of the literature on this disease is discussed. Conclusion Myositis Ossificans is characterized by aberrant bone formation typically occurring after trauma but may be secondary to an underlying genetic abnormality. The case presented in the absence of trauma or an underlying genetic abnormality and is therefore an exceedingly rare instance of the sporadic form that presented spontaneously in the head and neck of a pediatric patient.