• Adult
• Humans
• Brain/diagnostic imaging
• Brain/pathology
• Magnetic Resonance Imaging

Ethanol is the most consumed drug worldwide, even during pregnancy. One of its adverse outcomes is fetal growth restriction, an alteration in development due to decreased IGF-1 levels. Several studies have shown that ethanol can impair the IGF-1 signaling pathway, thus exacerbating IGF-1 adverse effects in both intrauterine and postnatal growth and development. In this manuscript, we used a partially IGF-1-deficient mouse model to demonstrate the key role of IGF-1 in fetal development, as well as ethanol’s adverse effects on CYP2E1 expression levels and the antioxidant enzyme system during pregnancy.

Ethanol use during pregnancy is a risk factor for developing adverse outcomes. Its metabolism by cytochrome P450 2E1 (CYP2E1) produces radical oxygen species (ROS), promoting cellular injury and apoptosis. To date, no studies have been conducted to elucidate the teratogenic effects due to both IGF-1 deficiency and ethanol consumption in mice placentas. The aim of this study is to determine the effect of ethanol consumption on the placenta and liver of partially IGF-1-deficient mice, the role of metabolism via CYP2E1, and the antioxidant enzyme system. Heterozygous (HZ, Igf1^+/−) pregnant female mice were given water or 10% ethanol. Wild-type (WT, Igf1^+/+) female mice were used as controls. At gestational day 19, pregnant dams were euthanized, and maternal liver and placentas were collected. Pregnant HZ dams were smaller than controls, and this effect was higher due to ethanol consumption. Cyp2e1 gene was overexpressed in the liver of HZ pregnant dams exposed to ethanol; at the protein level, CYP2E1 is reduced in placentas from all genotypes. The antioxidant enzymatic system was altered by ethanol consumption in both the maternal liver and placenta. The results in this work hint that IGF-1 is involved in intrauterine development because its deficiency exacerbates ethanol’s effects on both metabolism and the placenta.

Laron syndrome (LS) is a rare autosomal recessive disorder characterized by dwarfism and typical facial phenotype. This report is the first to present three cases of Laron syndrome affecting three female siblings from Syria. The index case presented at age of 8.5 years with severe short stature: low level of Insulin-like growth factor 1 (IGF-1), elevated levels of fasting and post-stimulation growth hormone (GH), consistent with the diagnosis of Laron syndrome. At the age of 9.5 years, she developed non-autoimmune subclinical hypothyroidism treated with Levothyroxine, then she developed dyslipidemia at the age of 11.3 years. Later, we identified two female siblings of the patient with Laron syndrome. Laron syndrome is a rare genetic disease, reporting of new cases of this rare syndrome must encourage pediatricians to develop high clinical suspicion if faced with patients with very short stature and typical facial features.

• Laron syndrome
• dwarfism
• dyslipidemia
• hypothyroidism

• Case report
• Embryo diagnosis
• Growth hormone insensitivity
• Growth hormone receptor mutations
• Intragenic deletions
• Laron syndrome
• Molecular diagnosis

Glucose and lipid profile together with blood pressure should always be considered for low sera‐IGF‐1 patients. Even when adulthood is reached, IGF‐1 therapy in these patients should be pursued as metabolic and protective cellular effects could be triggered. Real incidence of growth hormone insensitivity is still to be uncovered.

• GH insensitivity
• GH/IGF‐1 axis
• GHR
• IGF‐1
• Laron syndrome
• metabolic syndrome
• obesity
• stroke
• type 2 diabetes