Elizabeth Varga

Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE): Awareness and Prophylaxis Practices Reported by Patients with Cancer

Patients with cancer are at increased risk for venous thromboembolism (VTE). An online survey to measure PE/DVT terminology awareness and understanding of VTE risks revealed 24% and 15% of the 500 cancer patients surveyed had heard of term DVT/PE; 19% and 17% could name signs/ symptoms of DVT/PE; 3% recognized cancer treatments as risk factors for DVT/PE. Only 25% of the patients received prevention education from providers; <50% received VTE prophylaxis. Cancer patient awareness of VTE terminology and cancer and/or its treatment as risk for VTE is low. More effective patient/physician dialogue about VTE risk and thromboprophylaxis is needed.

MTHFR: Addressing Genetic Counseling Dilemmas Using Evidence-Based Literature

The 5, 10 methylenetetrahydrofolate reductase (MTHFR) enzyme is a catalyst in the folate metabolism pathway, the byproducts of which are involved in the remethylation of homocysteine to methionine. Methionine is a precursor for a major DNA methyl donor and is important for DNA methylation and gene regulation. Rare mutations in the MTHFR gene have been associated with autosomal recessive MTHFR deficiency leading to homocystinuria. In addition, two polymorphic variants in this gene (C677T and A1298C) have been implicated in a mild form of MTHFR deficiency associated with hyperhomocysteinemia. Mild to moderate hyperhomocysteinemia has been previously implicated as a risk factor for cardiovascular disease. Further, the presence of these variants, with and without mildly elevated levels of homocysteine, has been studied in relation to several multifactorial disorders including recurrent pregnancy loss, neural tube defects and congenital anomalies, cancer, and neurodevelopmental disorders. Given this wide spectrum of purported clinical implications and the prevalence of these polymorphisms, genetic counselors may encounter questions regarding the significance of MTHFR polymorphisms in a variety of settings. Here we present a brief background of the MTHFR polymorphisms, review of the literature regarding clinical considerations, and discussion of relevant genetic counseling aspects through case vignettes. Educational resources for patients and providers are also included.

SHH desmoplastic/nodular medulloblastoma and Gorlin syndrome in the setting of Down syndrome: case report, molecular profiling, and review of the literature

IntroductionIndividuals with Down syndrome (DS) have an increased risk of acute leukemia compared to a markedly decreased incidence of solid tumors. Medulloblastoma, the most common malignant brain tumor of childhood, is particularly rare in the DS population, with only one published case. As demonstrated in a mouse model, DS is associated with cerebellar hypoplasia and a decreased number of cerebellar granule neuron progenitor cells (CGNPs) in the external granule cell layer (EGL). Treatment of these mice with sonic hedgehog signaling pathway (Shh) agonists promote normalization of CGNPs and improved cognitive functioning.Case reportWe describe a 21-month-old male with DS and concurrent desmoplastic/nodular medulloblastoma (DNMB)—a tumor derived from Shh dysregulation and over-activation of CGNPs. Molecular profiling further classified the tumor into the new consensus SHH molecular subgroup. Additional testing revealed a de novo heterozygous germ line mutation in the PTCH1 gene encoding a tumor suppressor protein in the Shh pathway.DiscussionThe developmental failure of CGNPs in DS patients offers a plausible explanation for the rarity of medulloblastoma in this population. Conversely, patients with PTCH1 germline mutations experience Shh overstimulation resulting in Gorlin (Nevoid Basal Cell Carcinoma) syndrome and an increased incidence of malignant transformation of CGNPs leading to medulloblastoma formation. This represents the first documented report of an individual with DS simultaneously carrying PTCH1 germline mutation.ConclusionWe have observed a highly unusual circumstance in which the PTCH1 mutation appears to “trump” the effects of DS in causation of Shh-activated medulloblastoma.

Thrombocytopenia Pitfalls: Misdiagnosing Type 2B von Willebrand Disease as Ethylenediaminetetraacetic Acid-Dependent Pseudothrombocytopenia.

A 9-month-old boy was referred to our emergency department for extensive bruising. Medical history was relevant for increased bleeding postcircumcision and vaccination. Baseline coagulation laboratory values were normal, and a complete blood count revealed severe thrombocytopenia (Table; available at www.jpeds.com). Review of peripheral smear revealed platelet clumps, presumed to be ethylenediaminetetraacetic acid (EDTA)-dependent pseudothrombocytopenia (PTCP) (Figure). The severity of bruising raised suspicion for nonaccidental trauma, prompting the involvement of child protection services. The hemostasis-thrombosis team was consulted and additional coagulation laboratory values revealed low von Willebrand factor (vWF) antigen (32%) and ristocetin cofactor activity (<8%). vWF multimer analysis showed loss of high-molecular-weight multimers, suggesting a diagnosis of type 2B von Willebrand disease (vWD). Findings of nonaccidental trauma testing (skeletal survey, computed tomography brain scan, and ophthalmology examination) were negative. vWF exon 28 gene sequencing confirmed a sequence variant in the A1 domain, c.3940G>C, p.V1314L, which is associated with type 2B vWD.

Sickle cell trait knowledge and health literacy in caregivers who receive in‐person sickle cell trait education

Despite universal screening that detects sickle cell trait (SCT) in infancy, only 16% of Americans with SCT know their status. To increase SCT status awareness, effective education for patients and their families is needed. The objective of this study was to assess caregivers’ SCT knowledge before and after an in‐person SCT education session.