Endocrine Abstracts

Introduction: Adipose tissue is recognized as an important endocrine organ, secreting many endocrine factors. Adiponectin is the most abundant peptide released into circulation, encoded by ADIPOQ gene localized in chromosome 3q27.3. Adiponectin decreases intracellular ceramide, implicated in insulin resistance, inflammation and atherosclerosis. It stimulates fatty acid oxidation in skeletal muscle and inhibits glucose production in the liver. Hypo-adiponectinemia plays a central role in obesity and obesity-related disease. Since the advent of Comparative Genomic Hybridization Array (CGH-Array), numerous new microdeletional syndromes have been described. Few cases of autosomal dominant 3q27.3 microdeletion syndrome have been described, mostly characterized by intrauterine growth retardation, marfanoid habitus, cranio-facial dysmorphism, intellectual disability, psychosis and mood disorder. We describe a family affected by 3q27.3 microdeletion involving ADIPOQ gene, adding obesity and obesity-related disease to constellation of major clinical findings reported in 3q27.3 microdeletion syndrome.

Case Study: A 21-year-old Caucasian male underwent genetic investigation by CGH-Array during a diagnostic study for familiar schizoid-type personality disorder, cognitive delay, macrocephaly and thickening of skull cap. Array analysis revealed a 1.43-Mb deletion in the long arm of chromosome 3 (3q27.3), including ADIPOQ gene and other two OMIM disease genes (KNG1 and BCL6). The analysis was then extended to parental couple, demonstrating the paternal origin of the rearrangement. Afterwards, same microdeletion was demonstrated in his 26-year-old sister. Deletions were confirmed by fluorescent in situ hybridization. All family members shared a complex syndromic clinical spectrum consisting of severe neuropsychiatric impairment, schizoid-type personality disorder, cognitive delay and thickening of skull cap, signs compatible with other clinical findings reported in literature for 3q27.3 microdeletion. No marfanoid habitus was reported, even though all had history of ligament laxity-related disorders. All three members of the family shared moderate-severe hyperphagia, early central obesity, marked hyperinsulinemia, obstructive sleep apnea syndrome, arterial hypertension, dyslipidemia and hepatosplenomegaly with hepatic steatosis, composing a new syndromic frame in the context of 3q27.3 microdeletion syndrome.

Discussion: This new clinical spectrum associated with 3q27.3 microdeletion involving ADIPOQ gene reinforce a suggested role of adiponectin haploinsufficiency in central obesity, atherogenic metabolic status, fat accumulation in the liver and dyslipidemia. A possible role of adiponectin on food intake at hypothalamic level is also suggested. The involvement of adjacent loci and genes, such as OMIM genes, may contribute to these novel features in 3q27.3 microdeletion syndrome. The fewer number of bases involved, 1.43-Mb vs >5-Mb described in literature, could explain the absence of some syndromic features.