Context: Antiphospholipid syndrome (APS or Hughes’ syndrome) is a systemic autoimmune disorder characterized by antiphospholipid antibodies (aPLs) positivity which may lead to arterial and/or venous thrombosis. Hyper-homocysteinemia (HHcy), variously associated with 5,10-methylene tetrahydrofolate reductase (MTHFR) gene point mutations, is also implicated in thromboembolic events. The association of APS and HHcy has already been described but never reported in patients with DiGeorge syndrome (DGS), the most common contiguous-gene deletion syndrome (22q11.2) in humans, whose phenotype conversely includes bleeding disorders.

Data Acquisition: In this report, we present the case of a 19 yr-old patient with a past medical history of learning disability and obesity affected with idiopathic hypoparathyroidism, metabolic syndrome and diffuse vasculitis disorders. He was referred to our Endocrinology clinic for the management of severe hypocalcemia. At the time of presentation he was taking anti-epileptic drugs for 2 weeks and displayed facial dysmorphism (short neck, micrognathia, a small mouth, hypoplastic nasal alae, eye hypertelorism and low-set simple ears). DiGeorge syndrome (DGS) was suspected and confirmed by both fluorescence in-situ hybridization analysis (FISH) and single nucleotide polymorphism-array (SNP) analysis which revealed contiguous gene microdeletion of the chromosome 22q11.2 in the minimal DiGeorge critical region (MDGCR), specifically at the gene locus D22S75 (N25).

Conclusions: APS, revealed by anti-beta-2-glycoprotein (anti-2-GPI) and anti-prothrombin (anti-PT) antibodies positivity, and moderate HHcy related to heterozygous C677T and A1298C point mutations of the MTHFR gene, were identified as a possible cause of thrombotic disorder responsible for the widespread presence of cutaneous and cerebral lesions.