The aim of our study was to measure, at delivery, maternal and cord blood cadmium levels (by means of atomic absorption spectrometry) in 45 healthy non-smoking pregnant women exposed to a low cadmium challenge, and to evaluate the relationship between these cadmium levels and the birth weight of the infants. Our results showed fairly low cadmium levels in maternal blood, in accordance with the fact that all women enrolled in this study lived in areas with low toxic metal contamination and that they did not smoke during their pregnancy. Furthermore, a highly significant direct correlation was found between maternal and cord blood cadmium concentrations. Since cadmium concentration appeared of the same order of magnitudine both in cord and maternal serum, one could speculate that cadmium is transferred easily from the mother to the fetus through the placenta. Finally, we found that birth weight is inversely correlated with maternal and cord blood cadmium concentrations; thus birth weight might be negatively influenced by cadmium levels as a result of the toxic effects of the metal on the placenta. Although preliminary, our data show that (also not-predictable) prenatal exposure to even low cadmium levels might be a risk factor for developmental impairment in infants.

Cardio-facio-cutaneous syndrome (CFCS) is a rare disease characterized by mental retardation, facial dysmorphisms, ectodermal abnormalities, heart defects and developmental delay. CFCS is genetically heterogeneous and mutations in the KRAS, BRAF, MAP2K1 (MEK1) and MAP2K2 (MEK2) genes, encoding for components of the RAS–mitogen activated protein kinase (MAPK) signaling pathway, have been identified in up to 90% of cases. Here we screened a cohort of 33 individuals with CFCS for MEK1 and MEK2 gene mutations to further explore their molecular spectrum in this disorder, and to analyze genotype–phenotype correlations. Three MEK1 and two MEK2 mutations were detected in six patients. Two missense MEK1 (L42F and Y130H) changes and one in-frame MEK2 (K63_E66del) deletion had not been reported earlier. All mutations were localized within exon 2 or 3. Together with the available records, the present data document that MEK1 mutations are relatively more frequent than those in MEK2, with exons 2 and 3 being mutational hot spots in both genes. Mutational analysis of the affected MEK1 and MEK2 exons did not reveal occurrence of mutations among 75 patients with Noonan syndrome, confirming the low prevalence of MEK gene defects in this disorder. Clinical review of known individuals with MEK1/MEK2 mutations suggests that these patients show dysmorphic features, ectodermal abnormalities and cognitive deficit similar to what was observed in BRAF-mutated patients and in the general CFCS population. Conversely, congenital heart defects, particularly mitral valve and septal defects, and ocular anomalies seem to be less frequent among MEK1/MEK2 mutation-positive patients.

To date cytokines profile in AEDS is poorly described in children. We evaluated the interleukin (IL)-17, IL-23, and IL-10 levels in atopic eczema/dermatitis syndrome (AEDS) children and healthy controls, in atopic AEDS (aAEDS) and nonatopic (naAEDS) subtypes and their relationship with disease severity. A total of 181 children with aAEDS and 93 healthy children were evaluated. According to the skin-prick test (SPT) for allergens and serum total IgE, all patients were subdivided in two groups: 104 aAEDS and 77 naAEDS. In all patients, serum IL-17, IL-23, and IL-10 levels were detected. Serum IL-17 and IL-23 levels were significantly higher, and serum IL-10 levels were significantly lower in AEDS children than healthy group (p < 0.001). Moreover, serum IL-17 and IL-23 levels were significantly higher in aAEDS than in naAEDS subtypes (p < 0.001). Differently, serum IL-10 levels resulted similar in both subtypes. There was a correlation between Score Atopic Dermatitis (SCORAD) index and both IL-17 and IL-23 and an inverse correlation between SCORAD index and IL-10 in aAEDS and naAEDS types. Serum IL-17 and IL-23 values were positively related to total IgE levels (p < 0.0001) in aAEDS. Further increase of IL-17 and IL-23 levels was detected in aAEDS subjects with atopic diseases such as asthma and rhinitis than children with only allergic sensitization. Our study confirms the role of IL-17, IL-23, and IL-10 and their relationship with the severity of AEDS. We firstly found a correlation between high IL-17/IL-23 axis levels and different phenotypes of AEDS in children, suggesting its role as marker of “atopic march” and disease severity.