A novel ABCC9 variant in a Greek family with Cantu syndrome affecting multiple generations highlights the functional role of the SUR2B NBD1.

Cantu syndrome (CS) (OMIM #239850) is an autosomal dominant multiorgan system condition, associated with a characteristic facial phenotype, hypertrichosis, and multiple cardiovascular complications. CS is caused by gain-of-function (GOF) variants in KCNJ8 or ABCC9 that encode pore-forming Kir6.1 and regulatory SUR2 subunits of ATP-sensitive potassium (KATP) channels. A novel heterozygous ABCC9 variant, c.2440G>T; p.Gly814Trp, was identified in three individuals from a four generation Greek family. The membrane potential in cells stably expressing hKir6.1 and hSUR2B with p.Gly814Trp was hyperpolarized compared to cells expressing WT channels, and inside-out patch-clamp assays of KATP channels formed with hSUR2B p.Gly814Trp demonstrated a decreased sensitivity to ATP inhibition, confirming a relatively mild GOF effect of this variant. The specific location of the variant reveals an unrecognized functional role of the first glycine in the signature motif of the nucleotide binding domains in ATP-binding cassette (ABC) protein ion channels.

A Comprehensive Multidisciplinary Management Plan Is Effective in Reducing the Prevalence of Overweight and Obesity in Childhood and Adolescence.

BACKGROUND: Obesity in childhood and adolescence represents a major health problem of our century. In Greece, 30-35% of children and adolescents are overweight or obese. Objective and Hypotheses: To investigate the effectiveness of a comprehensive multidisciplinary personalized management plan at reducing the prevalence of overweight and obesity in childhood and adolescence. PATIENTS AND METHODS: One thousand (n = 1,000) children and adolescents aged 2-18 years (mean age ± SD: 10.09 ± 2.86 years; 520 females, 480 males) were studied prospectively. Subjects were classified as obese (n = 579, 57.9%), overweight (n = 295, 29.5%) or having a normal body mass index (BMI) (n = 126, 12.6%) according to the International Obesity Task Force cutoff points. All subjects were evaluated by a multidisciplinary team at frequent intervals, received personalized advice on diet and exercise and were studied prospectively for 1 year. Detailed clinical evaluation and laboratory investigations were performed at the beginning and at the end of the study. RESULTS: At initial evaluation, 57.9% of subjects were obese, 29.5% overweight and 12.6% of normal BMI. Indices of cardiometabolic disease were higher in obese than in overweight and normal-BMI subjects. Following 1 year of multidisciplinary management interventions, the prevalence of obesity decreased by 16.8%, the prevalence of normal BMI increased by 8.2%, and all cardiometabolic indices improved significantly. CONCLUSIONS: A personalized multidisciplinary management plan is effective at reducing the prevalence of obesity in childhood and adolescence.

Viral croup: diagnosis and a treatment algorithm.

Viral croup is a frequent disease in early childhood. Although it is usually self-limited, it may occasionally become life-threatening. Mild croup is characterized by the presence of stridor without intercostal retractions, whereas moderate-to-severe croup is accompanied by increased work of breathing. A single dose of orally administered dexamethasone (0.15-0.6 mg/kg) is the mainstay of treatment with addition of nebulized epinephrine only in cases of moderate-to-severe croup. Nebulized budesonide (2 mg) can be given alternatively to children who do not tolerate oral dexamethasone. Exposure to cold air or administration of cool mist are treatment interventions for viral croup that are not supported by published evidence, but breathing heliox can potentially reduce the work of breathing related to upper airway obstruction. In summary, corticosteroids may decrease the intensity of viral croup symptoms irrespective to their severity on presentation to the emergency department.