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Breast development was normal. At the age of 16 years, her height was 168?cm (?0.26 SDS) and weight 38.7?kg (?3 SDS). Both lenses were removed at this age. On the right eye an artificial lens was implanted. A contact lens on the left side was adapted. Homocystinuria was ruled out by normal urinary and serum amino-acid analysis. Echocardiography revealed an accessory left-sided vena cava inferior joining the intrathoracic azygous vein. Magnetic resonance imaging (MRI) imaging of the aorta showed a dilated aortic bulb (maximal diameter 32?mm), which was above the 97th centile for body surface [Poutanen Selleck HSP inhibitor et al., 2003] and a normal appearing ascending aorta, aortic arch, and thoracic descending aorta. At the age of 24 years, a deviation of the nasal septum was surgically corrected. The proposita had a progeroid appearance with extreme lack of subcutaneous fat, including her face. Therefore, an autologous injection of fat tissue from the thighs into the cheeks was performed at the age of 24 years (Fig. 3A). At physical examination at the age of 25 years, her height was 170?cm (?0.6 SDS), her weight was 39?kg (?5.2 SDS), and the head circumference was 53?cm (?1.17 SDS). Span-to-height ratio was 0.99 (positive?>?1.05), upper segment/lower segment 0.95 (positive?http://www.selleckchem.com a mildly kyphotic posture without scoliosis. The scapulae appeared winged. (Fig. 3B�CF). There was mild hyperextensibility of the finger joints but no other joint hyperextensibility. The veins were translucent especially in the calves. The skin was soft and displayed multiple pigment naevi. The skin over the hands was dry, thin, and atrophic. At the age Ibrutinib of 27 years, the diameter of the aortic bulb had increased to 35?mm (97th centile for body surface) [Biaggi et al., 2009]. No premature greying of hair was observed. Wound healing was normal. She showed a mild tendency to hematomas. Severe myopia had increased to ?20 diopters bilaterally, associated with a reduced visual acuity (50% on the right eye, about 70% on the left). Tear production was decreased due to xerophthalmia. The neurological examination was unremarkable, and the patient had no clinical signs of myopathy. Ultrasound examination was unremarkable. There were no signs of fatty liver or fatty pancreas, splenomegaly, atherosclerosis or polycystic ovaries. Lumbosacral dural ectasia was verified by MRI (see Fig. 4). Anteroposterior X rays ruled out protrusio acetabuli. Karyotype was normal female (46, XX), array CGH using an oligonucleotide array (244K, Agilent Technologies, Santa Clara, CA) with a genome wide resolution of 70�C100?kb did not detect any clinically relevant abnormalities.