The prevalence of obstructive sleep apnoea and its association with aortic dilatation in Marfan's syndrome.

BACKGROUND: Craniofacial abnormalities and increased pharyngeal collapsibility due to abnormal connective tissue suggest the possibility of an increased prevalence of obstructive sleep apnoea (OSA) in patients with Marfan's syndrome but the actual prevalence is uncertain. Aortic dilatation and dissection are life threatening manifestations of Marfan's syndrome and case reports have suggested a possible association with OSA but data from cohort studies are not available. METHODS: A sleep study was performed in 61 patients with Ghent criteria positive Marfan's syndrome (mean age 38.3 (SD 12.9) years; 37 females) and in 26 control subjects matched for age, gender, height and weight. OSA was defined using two conventional levels of apnoea-hypopnoea index (AHI), >5 and >15/h. In patients with Marfan's syndrome, aortic root diameter was measured by echocardiography. RESULTS: More patients with Marfan's syndrome than controls had OSA (AHI >5, 32.8% compared with 11.5%, mean difference +21.3%, 95% CI 4.2% to 38.3%, p = 0.04; AHI >15, 18.0% compared with 0%, mean difference +18.0%, 95% CI 8.4% to 27.7%, p = 0.02). AHI was correlated with aortic root diameter (r = 0.50, 95% CI 0.26 to 0.69, p = 0.0003), and mean aortic root diameter was significantly greater in patients with OSA (4.5 (SD 0.6) cm) compared with those without OSA (3.7 (0.6) cm) (mean difference 0.8 cm, 95% CI 0.4 to 1.2 cm, p<0.0001). CONCLUSIONS: In patients with Marfan's syndrome, the prevalence of OSA is considerably higher than in matched control subjects. OSA may be a risk factor for aortic root dilatation in Marfan's syndrome.

Refining the Amsterdam Criteria and Bethesda Guidelines: testing algorithms for the prediction of mismatch repair mutation status in the familial cancer clinic.

PURPOSE: Hereditary nonpolyposis colon cancer (HNPCC) is a Mendelian dominant syndrome of bowel, endometrial, and other cancers and results from germline mutations in mismatch repair (MMR) genes. HNPCC is now best diagnosed on molecular grounds using MMR mutation screening, aided by microsatellite instability (MSI) and immunohistochemistry in tumors. Selection of families for molecular investigation of HNPCC is usually based on suboptimal methods (Amsterdam Criteria or Bethesda Guidelines), but these can be improved using additional clinical data (mean ages of affected persons and presence of endometrial cancer) in a quantitative model. METHODS: We have verified the performance of the Wijnen model and have shown that it remains valid when HNPCC is diagnosed using mutation screening, MSI, and immunohistochemistry. We have also set up and verified our own models (Amsterdam-plus and Alternative), which perform at least as well as the Wijnen model. RESULTS: The Amsterdam-plus model improves on the Amsterdam Criteria by using five extra variables (numbers of colorectal and endometrial cancers in the family, number of patients with five or more adenomas, number with more than one primary cancer of the colorectum or endometrium, and mean age of presentation) and performs better than the Wijnen model. The Alternative model avoids the need to evaluate the Amsterdam Criteria and performs nearly as well as the other models. CONCLUSION: We believe that a quantitative model, such as the Amsterdam-plus model, should be the first choice for selecting families or patients for evaluation of HNPCC using molecular tests. We present an algorithm for this process.