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

Experimental application of a biomaterial in bifocal transport osteogenesis for craniofacial reconstruction

Purpose: Bifocal transport osteogenesis is an alternative technique of callus distraction, in which movement of a transport segment results in the formation of new bone in order to close a continuity defect. The aim of this experimental pilot study was to replace a bone graft by a biomaterial as a transport segment. Material and methods: Critical size defects of the calvaria in four adult sheep were treated with transport segments consisting either of an autogenous free bone graft of the calvaria (n = 2) or of the biomaterial (deproteinized bovine cancellous bone; n = 2). Latency period was 5 days; the rate of distraction was I mm per day and was planned for 40 days. The consolidation period was 28 days. Specimens were investigated by conventional radiography, CT-scans and histologically, including immunofluorescence. Results: In both groups, transport osteogenesis resulted in a "de novo" formation of bone, indicating that this biomaterial may contribute successfully to bone formation in bifocal transport osteogenesis. However, volume and thickness of the newly formed bone at the defect site were smaller when using the biomaterial than when using autogenous bonegrafts. Conclusion: The application of a biomaterial as transport segments in bifocal transport osteogenesis in cranial critical size defects resulted in the formation of new bone thus excluding bone graft donor site morbidity. (C) 2008 European Association for Cranio-Maxillofacial Surgery

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