Cardiology clinic patient attitudes toward and potential personal utility of genetic testing: Findings from a unique multiracial clinical sample.

As more is understood about the hereditary nature of disease risk, the utility of genetic testing within cardiovascular medicine is increasingly being explored. Although testing may afford more personalized risk stratification, there is a paucity of information regarding patient knowledge, attitudes, and beliefs toward genetic testing among cardiology patients. Participants (n = 530) recruited primarily from a cardiology clinic filled out a 41-item written questionnaire assessing knowledge, beliefs, and attitudes toward genetic testing, motivators and detractors for considering genetic testing, and perceived likelihood for behavior change after hypothetical genetic testing risk stratification. Path analysis was used to test the hypothetical models predicting the likelihood of getting a genetic test and making behavior changes following genetic testing. The patient population was late-middle-aged (59.0 ± 14.5 years), majority women (61.5%), and about half reported having a bachelor's degree. 58.1% of participants self-identified as White, 25.7% as African American or Black, 6.8% as Spanish, Latino, or Hispanic, 3.0% as Asian or Pacific Islander, and 0.5% as Native American. Gender (being a woman) and more years of education were related to greater knowledge about genetic testing. Racial identity and years of education were related to beliefs about genetic testing. Beliefs, but not knowledge, were related to more positive attitudes and a higher likelihood of pursuing genetic testing. Positive attitudes were related to greater perceived personal control (PPC). Furthermore, attitudes and PPC were related to higher likelihood of lifestyle change after genetic testing. These results highlight the need to integrate the experiences of racialized communities into education/counseling efforts. Most educational counseling efforts lack a nuanced discussion of social determinants of health or beliefs. In addition to factual information, educational counseling must also address people's beliefs, concerns, and the intersecting experiences and identities, which shape patients' relationships with the evolving landscape of healthcare and personalized medicine.

Utility of Neonatal Findings in Early Diagnosis of a Case of Haberland Syndrome.

Haberland syndrome or encephalocraniocutaneous lipomatosis (ECCL) is a rare, congenital syndrome characterized by lipomas and noncancerous tumors of the scalp, skin, and eyes, in addition to intellectual disability, early onset seizures, and ectomesodermal dysgenesis. The diagnosis of ECCL is classically made by clinical presentation, imaging, and histopathological findings, but due to the spectrum of clinical presentation and symptom severity, diagnosis is often delayed until adolescence or adulthood. Here we present a newborn male infant, one of the earliest case diagnoses to our knowledge, with a unique constellation of physical exam and neuroimaging findings consistent with this diagnosis. We aim to address important neonatal findings to aid in early detection and diagnosis of this unique disease, which is thought to improve clinical outcomes and patient quality of life.

Complicated ventricular arrhythmia and hematologic myeloproliferative disorder in RIT1-associated Noonan syndrome: Expanding the phenotype and review of the literature.

BACKGROUND: Noonan syndrome is an autosomal dominant disorder secondary to RASopathies, which are caused by germ-line mutations in genes encoding components of the RAS mitogen-activated protein kinase pathway. RIT1 (OMIM *609591) was recently reported as a disease gene for Noonan syndrome. METHODS AND RESULTS: We present a patient with RIT1-associated Noonan syndrome, who in addition to the congenital heart defect, had monocytosis, myeloproliferative disorder, and accelerated idioventricular rhythm that was associated with severe hemodynamic instability. Noonan syndrome was suspected given the severe pulmonary stenosis, persistent monocytosis, and "left-shifted" complete blood counts without any evidence of an infectious process. Genetic testing revealed that the patient had a heterozygous c.221 C>G (pAla74Gly) mutation in the RIT1. CONCLUSION: We report a case of neonatal Noonan syndrome associated with RIT1 mutation. The clinical suspicion for Noonan syndrome was based only on the congenital heart defect, persistent monocytosis, and myeloproliferative process as the child lacked all other hallmarks characteristics of Noonan syndrome. However, the patient had an unusually malignant ventricular dysrhythmia that lead to his demise. The case highlights the fact that despite its heterogeneous presentation, RIT1-associated Noonan syndrome can be extremely severe with poor outcome.

McArdle disease: a "pediatric" disorder presenting in an adult with acute kidney injury.

Rhabdomyolysis is characterized by the acute breakdown of skeletal muscle, resulting in the release of muscle cell contents, subsequent myoglobinuria, and in severe cases, acute renal failure. A number of etiologies have been identified in acute rhabdomyolysis, in which drugs and trauma account for the majority of cases. One etiological category that is commonly overlooked in the adult population is an underlying genetic defect. This may be challenging to diagnose due to its rarity in the adult demographic and the marked heterogeneity, often requiring a high level of clinical suspicion before investigation is pursued. Once diagnosed, however, appropriate steps can be taken to reduce future episodes of rhabdomyolysis, further renal injury, and other systemic complications. Here, we report a case of an adult patient presenting with acute rhabdomyolysis secondary to McArdle disease, a genetic disease causing defective glycogenolysis. The case highlights the importance of recognizing the potential of undiagnosed "pediatric" disorders in adulthood and particularly for underlying genetic causes of rhabdomyolysis.

Necrotizing enterocolitis in an infant with Omenn syndrome.

Omenn syndrome (OS) is a rare disorder within the combined immunodeficiency family that is characterized by a diffuse exudative, erythematous rash, lymphadenopathy, hepatosplenomegaly, alopecia, and failure to thrive. Specific lab findings unique to OS include hypereosinophilia, elevated IgE, excess production of oligoclonal T-cells and near-to-absent B-cells. Much remains elucidated about the underlying genetic cause of OS. Until recently, it was felt that the disease was primarily caused by mutations of the RAG1 or RAG2 genes. The type of mutation of the RAG1 and RAG2 genes in patients with OS affects the degree of functioning variable (diversity) joining [V(D)J] recombination activity, which is critical to the development of lymphoid cell receptor diversity. New work has also shown that thymic tissue in OS patients demonstrates a severe defect in the expression of the autoimmune regulator element. This may contribute to the development of autoreactive T-cells that are felt to be the causative agent of a number of the clinical hallmarks unique to OS. The genetic spectrum of OS was further expanded when a patient with clinical and immunologic features consistent with OS, without RAG mutation, was found to have mutations in both alleles coding for ARTEMIS, a key V(D)J recombination/DNA repair factor. Regardless of the underlying cause, early recognition is critical because patients die at a very young age without bone marrow transplantation. We describe an infant diagnosed with OS post-mortem in which death was directly related to the development of necrotizing enterocolitis.