SMARCAL1 deficiency predisposes to non-Hodgkin lymphoma and hypersensitivity to genotoxic agents in vivo.

Schimke immuno-osseous dysplasia (SIOD) is a multisystemic disorder with prominent skeletal, renal, immunological, and ectodermal abnormalities. It is caused by mutations of SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), which encodes a DNA stress response protein. To determine the relationship of this function to the SIOD phenotype, we profiled the cancer prevalence in SIOD and assessed if defects of nucleotide excision repair (NER) and nonhomologous end joining (NHEJ), respectively, explained the ectodermal and immunological features of SIOD. Finally, we determined if Smarcal1(del/del) mice had hypersensitivity to irinotecan (CPT-11), etoposide, and hydroxyurea (HU) and whether exposure to these agents induced features of SIOD. Among 71 SIOD patients, three had non-Hodgkin lymphoma (NHL) and one had osteosarcoma. We did not find evidence of defective NER or NHEJ; however, Smarcal1-deficient mice were hypersensitive to several genotoxic agents. Also, CPT-11, etoposide, and HU caused decreased growth and loss of growth plate chondrocytes. These data, which identify an increased prevalence of NHL in SIOD and confirm hypersensitivity to DNA damaging agents in vivo, provide guidance for the management of SIOD patients.

Demystifying radiation oncology clinical trial concerns for protocol scientific review and institutional review board committee members.

Clinical trials are essential for evaluating advanced technologies and treatment approaches involving radiation therapy to improve outcomes for cancer patients. Clinical trials at cancer centers with designation from the National Cancer Institute must undergo scientific review in additional to Institutional Review Board approval. Given the highly specialized nature and rapidly advancing technologies of radiation therapy, and the small number of radiation oncology investigators at some centers, a lack of radiation oncology expertise among reviewers may present challenges at some cancer centers. This commentary aims to provide an overview of radiation therapy and special considerations for radiation oncology research that will serve as a helpful resource in the scientific review of clinical trials involving cancer patients.

Low adherence to national guidelines for thyroid screening in Down syndrome.

PURPOSE: To determine adherence to the American Academy of Pediatrics guidelines for thyroid screening in children with Down syndrome among primary care providers in the states of Oklahoma and Nebraska. METHODS: We sought to identify all children with Down syndrome born in Oklahoma and Nebraska between 1994 and 2004 and review their medical records for evidence of thyroid screening. Patients were identified through a State Department of Health birth defects registry in Oklahoma and through participation in genetics clinics and laboratories in Nebraska and Oklahoma. Charts obtained from primary care providers were reviewed and the number of actual thyroid screens was compared with the number of recommended screens for each individual during the study period. RESULTS: In Oklahoma, 13% of participating children received all thyroid screens recommended in the guidelines. In Nebraska, 14% of children received all recommended thyroid screenings. Among participants in Oklahoma, a mean of 34% of recommended thyroid screenings were performed. In Nebraska, a mean of 45% of recommended thyroid screenings were performed. CONCLUSIONS: The level of adherence to the American Academy of Pediatrics guidelines for thyroid screening in children with Down syndrome is low. Factors contributing to this low level of adherence need to be identified and addressed.

Evaluation of a behavioral treatment package to reduce sleep problems in children with Angelman Syndrome.

The purpose of this investigation was to evaluate the effectiveness of a behavioral treatment package to reduce chronic sleep problems in children with Angelman Syndrome. Participants were five children, 2-11 years-of-age. Parents maintained sleep diaries to record sleep and disruptive nighttime behaviors. Actigraphy was added to provide independent evaluations of sleep-wake activity. The treatment package targeted the sleep environment, the sleep-wake schedule, and parent-child interactions during sleep times. Treatment was introduced sequentially, across families, and evaluated in an interrupted time series, multiple baseline design. Data show that prior to treatment, baseline rates of nighttime disruptive behavior were stable or increasing and none of the participants were falling to sleep independently. With the introduction of treatment, all participants quickly learned to initiate sleep independently. Gradual reductions were reported in disruptive behaviors and these improvements were sustained over time. Results were replicated with two participants when treatment was withdrawn and reinstated. Changes in disruptive bedtime behaviors and in sleep onset were found to be statistically significant. Parents indicated high satisfaction with the treatment. A behavioral treatment package was found to be effective with five children with long histories of significant sleep-related behavior problems. These results suggest that behavioral treatment may be a reasonable way to address sleep problems in some children with Angelman Syndrome.