Association of Polymorphisms in MACRO Domain Containing 2 With Thyroid-Associated Orbitopathy.

PURPOSE: Thyroid-associated orbitopathy (TO) is an autoimmune-mediated orbital inflammation that can lead to disfigurement and blindness. Multiple genetic loci have been associated with Graves' disease, but the genetic basis for TO is largely unknown. This study aimed to identify loci associated with TO in individuals with Graves' disease, using a genome-wide association scan (GWAS) for the first time to our knowledge in TO. METHODS: Genome-wide association scan was performed on pooled DNA from an Australian Caucasian discovery cohort of 265 participants with Graves' disease and TO (cases) and 147 patients with Graves' disease without TO (controls). Top-ranked single nucleotide polymorphisms (SNPs) then were genotyped in individual DNA samples from the discovery cohort, and two replication cohorts totaling 584 cases and 367 controls. RESULTS: In the GWAS of pooled DNA samples, several SNPs showed suggestive association with TO at genome-wide P ≤ 10-6; rs953128 located on chr10q21.1, rs2867161 on chr7q11.22, rs13360861 on chr5q12.3, rs7636326 on chr3q26.2, rs10266576 on chr 7q11.22, rs60457622 on chr3q23, and rs6110809 on chr20p12.1. However, the only SNP consistently associated with TO on individual genotyping in the discovery and replication cohorts was rs6110809, located within MACROD2 on chromosome 20p12.1. On combined analysis of discovery and replication cohorts, the minor A allele of rs6110809 was more frequent in TO than in Graves' disease controls without TO (P = 4.35 × 10-5; odds ratio [OR] = 1.77; 95% confidence interval [CI], 1.35-2.32) after adjusting for age, sex, duration of Graves' disease, and smoking. CONCLUSIONS: In patients with Graves' disease, a common genetic variant in MACROD2 may increase susceptibility for thyroid-associated orbitopathy. This association now requires confirmation in additional independent cohorts.

Orbital lipomatous haemangiopericytoma: an unusual variant.

Haemangiopericytoma (HPC) of the orbit is a rare tumour occurring in all age groups and presenting with slowly progressive proptosis, ocular motility impairment and visual loss. Although most are benign tumours that are resectable at diagnosis, one-third of these tumours demonstrate malignant features and recur locally or metastasize, usually with a fatal outcome. In 1995, a morphologically unique variant, termed lipomatous haemangiopericytoma (L-HPC), was described. Only one case has been reported previously arising in the orbit. In this paper, a case is reported of L-HPC occurring in the orbit and consider the prognostic implications of this HPC variant.

Orbital foreign body misdiagnosed as superior orbital rim fracture.

Orbital foreign bodies may be difficult to diagnose clinically and radiologically. In cases where a foreign body is suspected, both the mechanism of injury and the composition of the offending material need to be taken into account. A case is described of an orbital foreign body misdiagnosed as a superior orbital rim fracture, resulting in persistent ptosis and diplopia, and leading to delayed recovery for the patient, a commercial airline pilot.