3 research outputs found
Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility
Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes
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Accuracy of autorefraction in an adult Indian population.
PurposeAutorefractors allow non-specialists to quickly assess refractive error, and thus could be a useful component of large-scale vision screening programs. In order to better characterize the role of autorefraction for public health outreach programs in resource-limited settings, the diagnostic accuracy of two autorefractors was assessed relative to subjective refraction in an adult Indian population.MethodsAn optometrist refracted a series of patients aged ≥50 years at an eye clinic in Bangalore, India using the Nidek ARK-900 autorefractor first, followed by the 3nethra Royal autorefractor, and then subjective refraction. The diagnostic accuracy of each autorefractor for myopia, hyperopia, and astigmatism was assessed using subjective refraction as the reference standard, and measures of agreement between refractions were calculated.ResultsA total of 197 eyes in 104 individuals (mean age 63 ± 8 years, 52% female) were evaluated. Both autorefractors produced spherical equivalent estimates that were on average more hyperopic than subjective refraction, with a measurement bias of +0.16 D (95%CI +0.09 to +0.23D) for Nidek and +0.42 D (95%CI +0.28 to +0.54D) for 3nethra. When comparing pairs of measurements from autorefraction and subjective refraction, the limits of agreement were approximately ±1D for the Nidek autorefractor and ±1.75D for the 3Nethra autorefractor. The sensitivity and specificity of detecting ≥1 diopter of myopia were 94.6% (95%CI 86.8-100%) and 92.5% (95%CI 88.9-97.5%) for the Nidek, and 89.2% (95%CI 66.7-97.4) and 77.5% (95%CI 71.2-99.4%) for the 3Nethra. The accuracy of each autorefractor increased at greater levels of refractive error.ConclusionsThe sensitivity and specificity of the Nidek autorefractor for diagnosing refractive error among adults ≥50 years in an urban Indian clinic was sufficient for screening for visually significant refractive errors, although the relatively wide limits of agreement suggest that subjective refinement of the eyeglasses prescription would still be necessary