ABSTRACT
De novo heterozygous mutations changing R179 to histidine, leucine, or cysteine in the ACTA2 gene are associated with Multisystemic Smooth Muscle Dysfunction Syndrome (MSMDS). Characteristic hallmarks of this condition, caused only by these specific ACTA2 mutations, are congenital mydriasis (mid-dilated, non-reactive pupils), a large persistent ductus arteriosus (PDA), aortic aneurysms evolving during childhood, and cerebrovascular anomalies. We describe two patients, a 3-day-old newborn and a 26-year-old woman, with this unique mutation in association with a huge PDA and an aorto-pulmonary window. In addition, one showed a coarctation of the aortic arch and the other a complete interruption of the aortic arch type A; thereby expanding the spectrum of cardiac congenital heart defect of this syndrome. Each patient displayed a huge PDA and an extra-cardiovascular phenotype consistent with MSMDS. These observations exemplify that a functional alpha 2 smooth muscle actin is necessary for proper cardiovascular organ development, and demonstrate that a very exceptional congenital heart defect (aortopulmonary window) can be caused by a mutation in a gene encoding a contractile protein of vascular smooth muscle cells. © 2017 Wiley Periodicals, Inc.
Subject(s)
Actins/genetics , Aortic Aneurysm/pathology , Ductus Arteriosus, Patent/pathology , Eye Diseases, Hereditary/pathology , Heart Defects, Congenital/pathology , Mutation , Mydriasis/pathology , Adult , Aortic Aneurysm/diagnostic imaging , Aortic Aneurysm/genetics , Ductus Arteriosus, Patent/diagnostic imaging , Ductus Arteriosus, Patent/genetics , Eye Diseases, Hereditary/diagnostic imaging , Eye Diseases, Hereditary/genetics , Female , Gene Expression , Heart Defects, Congenital/diagnostic imaging , Heart Defects, Congenital/genetics , Heterozygote , Humans , Infant, Newborn , Magnetic Resonance Imaging , Muscle, Smooth/metabolism , Muscle, Smooth/pathology , Mydriasis/diagnostic imaging , Mydriasis/genetics , Phenotype , SyndromeABSTRACT
BACKGROUND AND PURPOSE: Transorbital sonography may help establish diagnosis of central retinal artery occlusion (CRAO). Next to Doppler sonographic proof of CRAO, an intra-arterial spot sign can be detected in some cases. We hypothesized that it reflects calcified components. It may be associated with embolization from atherosclerotic plaques and may negatively influence thrombolysis. METHODS: Prospective monocenter study of 46 patients with ophthalmologically confirmed CRAO. Systemic tissue-type plasminogen activator thrombolysis was performed when appropriate. All patients received etiologic workup. RESULTS: CRAO was confirmed by Doppler in all patients. Fifty-nine percent of patients with arterio-arterial embolization were spot sign-positive compared with 20% from cardiac source (P<0.05) and none with vasculitis. Eleven patients underwent thrombolysis. Clinically relevant visual improvement was only found in absence of a spot sign (P<0.05). CONCLUSIONS: Transbulbar ultrasound is valuable for initial diagnosis and diagnostic workup of CRAO. In the light of inconsistent results of previous thrombolysis trials, ultrasound may identify patients more likely to benefit from thrombolytic treatment.
Subject(s)
Retinal Artery Occlusion/diagnostic imaging , Retinal Artery Occlusion/drug therapy , Thrombolytic Therapy/trends , Ultrasonography, Doppler, Color/trends , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Treatment OutcomeABSTRACT
PURPOSE: To evaluate the outcomes of surgery for Brown syndrome. METHODS: We reviewed the charts of 15 patients who underwent surgery for Brown syndrome. The limitation of elevation in adduction (LEA) ranged from -2 to -4 degrees. A superior oblique muscle (SO) tenotomy was performed in 4 patients, a silicone expander was inserted in the SO of 9 patients, and a SO recession was performed in 2 patients. The results of surgery were analyzed with a follow-up period of more than 6 months, 42.3 +/- 48.42 months on average. RESULTS: Nine female patients and 6 male patients with unilateral Brown syndrome were selected for this study. The left eye was the affected eye in 9 patients. The degree of preoperative LEA was -2 to -4 in 4 patients in whom SO tenotomy was performed, -3 to -4 in 9 patients treated with the silicone expander, and -2 to -4 in 2 patients treated with SO recession. The LEA was released after surgery in all patients without postoperative adhesion. However, unilateral overaction of the inferior oblique muscle due to excessive weakening of the SO occurred in 1 patient with tenotomy (25%) and in 1 patient with insertion of a silicone expander (11%). CONCLUSIONS: LEA was released after tenotomy, insertion of a silicone expander and recession of the SO in 13 of 15 patients with Brown syndrome. SO palsy due to overcorrection and under-correction with postoperative adhesion should be avoided.
