Partial MEF2C deletion in a Cypriot patient with severe intellectual disability and a jugular fossa malformation: review of the literature.

Deletions or intragenic mutations involving the MEF2C gene on chromosome 5q14.3 have generally been associated with a relatively uniform phenotype characterized by severe developmental delay, absent speech, stereotypies, absent or limited gait abilities, lack of a typical facial gestalt and scarcity of major malformations. We report on a patient of Cypriot descent with a de novo, approximately 147 kb in size, partial MEF2C deletion removing exons 1 to 3. He had a history of severe intellectual disability with absent speech, poor eye contact, hand stereotypies and a wide-based gait. A broad-based, shallow jugular pit with an overlying vascular malformation was also present. Partial MEF2C deletions have only been reported in a very small number of patients and have on occasion been associated with relatively milder phenotypes. We present a patient of Cypriot descent with such a deletion and review previously published literature on partial MEF2C gene deletions postulating a key role of the first few exons in the pathogenesis of the disease.

Inherited metabolic disorders in Cyprus.

Selective screening for inherited metabolic disorders (IMD) began in Cyprus in 1990. Over the last thirty-three years 7388 patients were investigated for IMD and 200 diagnoses were made (diagnostic yield 2.7%). The existence of a single laboratory of Biochemical Genetics for the whole island facilitated the creation of a national registry for IMD. The minimal prevalence of IMD in Cyprus is 53.3 cases per 100,000 live births. The most common group are disorders of amino acid metabolism (41.0%), followed by disorders of carbohydrate metabolism (16.5%), disorders of complex molecule degradation (16.5%), mitochondrial disorders (10.5%) and disorders of vitamin and co-factor metabolism (5.5%). Hyperphenylalaninaemia is the most common IMD (14.0%) followed by galactosaemia (7.0%), glutaric aciduria type I (5.5%) and MSUD (4.0%). Some disorders were found to have a relatively high incidence in specific communities, for example Sandhoff disease among the Cypriot Maronites and GM1 gangliosidosis in one particular area of the island. Other disorders were found to have a relatively higher overall incidence, compared to other Caucasian populations, for example galactosaemia, glutaric aciduria type I and MSUD, while fatty acid oxidation defects, Gaucher disease and classic PKU were found to have a relatively lower incidence. Molecular characterization of selected disorders revealed many novel genetic variants, specific to the Cypriot population.

Asthma and atopy in children born by caesarean section: effect modification by family history of allergies - a population based cross-sectional study.

BACKGROUND: Studies on the association of birth by caesarean section (C/S) and allergies have produced conflicting findings. Furthermore, evidence on whether this association may differ in those at risk of atopy is limited. This study aims to investigate the association of mode of delivery with asthma and atopic sensitization and the extent to which any effect is modified by family history of allergies. METHODS: Asthma outcomes were assessed cross-sectionally in 2216 children at age 8 on the basis of parents' responses to the ISAAC questionnaire whilst skin prick tests to eleven aeroallergens were also performed in a subgroup of 746 children. Adjusted odds ratios of asthma and atopy by mode of delivery were estimated in multivariable logistic models while evidence of effect modification was examined by introducing interaction terms in the models. RESULTS: After adjusting for potential confounders, children born by C/S appeared significantly more likely than those born vaginally to report ever wheezing (OR 1.36, 95% CI 1.07-1.71), asthma diagnosis (OR 1.41, 95% CI 1.09-1.83) and be atopic (OR 1.67, 95% CI 1.08-2.60). There was modest evidence that family history of allergies may modify the effect of C/S delivery on atopy (p for effect modification=0.06) but this was not the case for the asthma outcomes. Specifically, while more than a two-fold increase in the odds of being a topic was observed in children with a family history of allergies if born by C/S (OR 2.62, 95% CI 1.38-5.00), no association was observed in children without a family history of allergies (OR 1.16, 95% CI 0.64-2.11). CONCLUSIONS: Birth by C/S is associated with asthma and atopic sensitization in childhood. The association of C/S and atopy appears more pronounced in children with family history of allergies.

Gender differences in objectively assessed physical activity in asthmatic and non-asthmatic children.

OBJECTIVE: To compare objectively assessed physical activity levels, between asthmatic children and non-asthmatic controls. METHODS: From a random community sample of 794 children aged 8-9 years, in a case-control design, 104 children with ever doctor's diagnosis of asthma and 99 non-asthmatic controls were recruited and had assessment of physical activity with biaxial accelerometers for 7 days. RESULTS: Children with active (also reporting at least one episode of wheezing in the last 12 months) and inactive (no wheezing in past 12 months) asthma appeared to have similar physical activity and sedentary activity levels compared to non-asthmatic children. However, girls with active asthma had significantly lower moderate-to-vigorous physical activity (MVPA) levels than their peers with adjusted geometric mean ratio of 0.59 (95% CI: 0.369, 0.929, P-value = 0.024). No difference in physical and sedentary activity levels was observed between asthmatic and non-asthmatic boys. The difference between genders in the comparison of MVPA levels in asthmatics and controls was statistically significant (P-value of likelihood ratio test [LRT] for effect modification by gender = 0.034). CONCLUSIONS: Unlike boys, girls with active asthma appear to be less active than their healthy peers, and this gender difference might explain the inconsistent evidence from previous reports on physical activity levels in asthmatic children. Further studies are needed to confirm the gender interaction in the childhood asthma-physical activity relation and the implications on current guidelines for physical exercise prescriptions in asthmatic children.