Pathogenic copy number variants and SCN1A mutations in patients with intellectual disability and childhood-onset epilepsy

Background Copy number variants (CNVs) have been linked to neurodevelopmental disorders such as intellectual disability (ID), autism, epilepsy and psychiatric disease. There are few studies of CNVs in patients with both ID and epilepsy. Methods We evaluated the range of rare CNVs found in 80 Welsh patients with ID or developmental delay (DD), and childhood-onset epilepsy. We performed molecular cytogenetic testing by single nucleotide polymorphism array or microarray-based comparative genome hybridisation. Results 8.8 % (7/80) of the patients had at least one rare CNVs that was considered to be pathogenic or likely pathogenic. The CNVs involved known disease genes (EHMT1, MBD5 and SCN1A) and imbalances in genomic regions associated with neurodevelopmental disorders (16p11.2, 16p13.11 and 2q13). Prompted by the observation of two deletions disrupting SCN1A we undertook further testing of this gene in selected patients. This led to the identification of four pathogenic SCN1A mutations in our cohort. Conclusions We identified five rare de novo deletions and confirmed the clinical utility of array analysis in patients with ID/DD and childhood-onset epilepsy. This report adds to our clinical understanding of these rare genomic disorders and highlights SCN1A mutations as a cause of ID and epilepsy, which can easily be overlooked in adults

Are we respecting the wishes of older persons who are living in residential aged care?

Older persons living in residential aged care are frequent users of ambulance services and hospital emergency departments (ED). A clinical audit of 300 randomly selected presentations from aged care to ED found that residents were often transferred to hospital against their values, preferences and directions expressed in their advance care plan or advance care directive. This submission to the Royal Commission into Aged Care Quality and Safety highlights problems with the number of different advance care planning forms in use as well as problems with interpretation of the documents

Food-based strategies improve iron status in toddlers: a randomized controlled trial12.

BACKGROUND: Nonanemic iron deficiency is common in toddlers in developed countries. Food-based strategies are safe methods to control and prevent mild micronutrient deficiencies. OBJECTIVE: Our objective was to determine the efficacy of an increased intake of red meat, or the consumption of iron-fortified milk, in improvement of iron status in toddlers at a population level. DESIGN: In this 20-wk randomized placebo-controlled trial, 225 healthy nonanemic 12-20-mo-old children were assigned to 1 of 3 groups: red meat (toddlers encouraged to consume approximately 2.6 mg iron from red meat dishes daily), fortified milk [toddlers' regular milk replaced with iron-fortified (1.5 mg iron/100 g prepared milk) cow milk], or control [toddlers' regular milk replaced with nonfortified (0.01 mg iron/100 g prepared milk) cow milk]. Blood samples were collected at baseline and at 20 wk for hemoglobin, serum ferritin, serum transferrin receptor, and C-reactive protein. The prevalence of suboptimal iron status (ie, depleted iron stores, iron-deficient erythropoiesis, and iron deficiency anemia) was determined, and body iron was calculated. RESULTS: No intervention effects were shown on the prevalence of suboptimal iron status. Serum ferritin increased by 44% (95% CI: 14%, 82%; P = 0.002) in the fortified milk group, did not change (+10%) in the red meat group (95% CI: -7%, 30%; P = 0.241), and tended to decrease (-14%) in the control group (95% CI: -27%, 1%; P = 0.063). By 20 wk, in comparison with the control group, serum ferritin and body iron were significantly higher in the fortified milk group (both P < 0.001), and serum ferritin was significantly higher in the red meat group (P = 0.033). CONCLUSIONS: Consumption of iron-fortified milk can increase iron stores in healthy nonanemic toddlers, whereas increased intakes of red meat can prevent their decline. This trial was registered at actr.org.au as ACTRN12605000487617