LHX4 Gene Alterations: Patient Report and Review of the Literature.

LHX4 mutations are rare in combined pituitary hormone deficiency, and even rarer in isolated GHD. We describe a 14 years old boy who was referred for investigation of short stature. Convergent strabismus, nystagmus was present. At the age of 5 years his gait was unstable. A progressive myopathy ensued. Tests of pituitary reserve showed partial IGHD (8.2 ng/ml). Other pituitary hormones were within normal range. Muscle biopsy showed congenital myopathy of undefined etiology. MRI of the brain revealed the empty sella syndrome. Targeted resequencing with a panel containing probe sets for enrichment and analysis of > 4,800 clinically relevant genes, targeting 12Mb of the human genome revealed the c.250C>T (R84C) LHX4 mutation. His father is healthy, with no myopathy or pituitary deficiencies, but has the same LHX4 mutation. This report extends the range of phenotypes associated with LHX4 gene mutations. To the best of our knowledge, we are the first to report on congenital myopathy in an LHX4 gene mutation. Forthwith, we offer a comprehensive review of the patients published so far with their clinical and genetic characteristics.

Prevalence of Overweight and Obesity in Children: Variation in Different Ethnicities, Age, and Sex in North Macedonia.

Childhood obesity is assuredly one of the most important health challenges of the 21st century, particularly regarding long-term metabolic complications. In the last four decades, there has been a tenfold increase in childhood and adolescence obesity. This cross-sectional study aimed to show the prevalence of overweight and obesity compared by age, sex, and ethnicity in n=1034 healthy male and female children, aged 6-13 years in North Macedonia. Out of the total 1034 children included in the study, 589 (57.0%) were observed with normal weight, 202 (19.5%) children were obese, 140 (13.5%) children were overweight and, 103 (10.0%) children underweight. The study presents an insight that 33% of primary school children are at >85th percentile overweight; or at ≥95th percentile with increased weight due to obesity. The data show that boys have a higher prevalence of obesity and overweight with 37.1%, compared to girls with 29.1%. Also, all age groups demonstrate an exponential increase of the prevalence of overweight: in 6-7 years (5.8%); 8-9 years (12%); 10-11 years (15%); and, 12-13 years old with 19.5%. A jump of prevalence of overweight and obesity between the age groups of 6-7 years, and 8-9 years was observed (17.9% to 25.4% obese and 5.8% to 12.0% overweight). The onset of puberty may be the possible cause. According to the Global Atlas of Childhood Obesity, North Macedonia is graded with a risk index of 7/11; i.e. it is expected that in the next decade until 2030 the obesity rate will rise to 52.5% for children aged 5-19 years old. It is with utmost importance to emphasize that continuous monitoring of children's nutritional status and their risk of obesity is essential, as to further prevent obesity and overweight in the pediatric population.

Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE) syndrome: CNS malformations and seizures may be a component of this disorder.

A newborn girl was found to have a massive lymphatic truncal vascular malformation with overlying cutaneous venous anomaly associated with overgrown feet and splayed toes. These manifestations comprise the recently described CLOVE syndrome. She also had cranial asymmetry and developed generalized seizures, which were treated with anticonvulsants. Cranial CT showed encephalomalacia, widening of the ventricles and the sulci, hemimegalencephaly (predominantly white matter) and partial agenesis of corpus callosum. Review of the literature identified several other patients with CLOVE syndrome, some of whom were misdiagnosed as having Proteus syndrome, with strikingly similar manifestations. We conclude that CNS manifestations including hemimegalencephaly, dysgenesis of the corpus callosum, neuronal migration defects, and the consequent seizures, may be an rarely recognized manifestation of CLOVE syndrome.