Hereditary Disorders Of Connective Tissue--Clinical And Molecular Studies

本研究探讨了结缔组织遗传性疾病的临床特征以及分子和生化相关因素；Marfan综合征，ehers - danlos综合征（EDS）和Stickler综合征，以及家族性动脉瘤综合征和纤维肌肉发育不良等相关疾病。到目前为止，大约有650名受试者参加了这项研究。根据霍尔特监测数据和血压测量的频域分析，在30%的EDS患者中记录有自主神经功能障碍，交感神经张力增加和直立性心动过速。骨密度测定研究表明，早发性骨质疏松和骨质减少在EDS和马凡氏病患者中非常常见，可能与特异性突变有关。颈椎和腰椎的MRI研究也在受试者身上进行。我们最近发现大约三分之一的患者有Chiari I畸形，85%的受试者有明显的脊柱异常，包括椎间盘突出、脊椎滑脱和硬脑膜扩张。我们注意到以前未被认识到的EDS并发症，包括EDS老年人类风湿性关节炎的发展（在我们的队列中占15%），临床显著睡眠障碍的发病率增加，以及与NHANES在所有年龄组中的平均水平相比，不利的脂质谱的高患病率。分析了HDCT中内分泌异常。大约30%患有血管性EDS和马凡氏综合征的男性性腺功能减退并伴有低骨密度。我们已经确定了一个家族性动脉瘤家族，其表型分离与COL5A1中过早停止密码子。一种以前未被认识到的结缔组织遗传性疾病，纤维肌肉发育不良（FMD）具有结缔组织特征，已在本研究的受试者中被发现。

This study examines the clinical features as well as molecular and biochemical correlates of heritable disorders of connective tissue; Marfan Syndrome, Ehlers-Danlos Syndrome (EDS) and Stickler Syndrome, as well as related disorders such as Familial Aneurysm Syndromes and Fibromuscular Dysplasia. To date, approximately 650 subjects have been enrolled in the study. Autonomic dysfunction with increased sympathetic tone and post orthostatic tachycardia has been documented in 30% of the subjects with EDS, based on frequency domain analysis of the Holter monitor data and blood pressure measurements. Bone densitometry studies have shown that premature osteoporosis and osteopenia are very common in the EDS and Marfan patients, and may be correlated with specific mutations. MRI studies of the cervical and lumbar spine are also carried out on subjects. We have recently found that approximately one third of patients have Chiari I malformations and 85% of the subjects have significant abnormalities pertaining to the spine including hernitated discs, spondylolisthesis, and dural ectasia. We have noted previously unrecognized complications of EDS, including the development of rheumatoid arthritis in older persons with EDS (in 15% of our cohort), increased incidence of clinically significant sleep disorders, and a high prevalence of unfavorable lipid profiles as compared to NHANES averages in all age groups. Endocrine abnormalities in HDCT have been analyzed. Approximately 30% of the males with Vascular EDS and Marfan syndrome have hypogonadism and accompanying low bone density. We have identified a Familial Aneurysm family where the phenotype segregates with a premature stop codon in COL5A1. A previously unrecognized hereditary disorder of connective tissue, fibromuscular dysplasia (FMD) with connective tissue features has been identified within subjects enrolled in the study. In the connective tissue cohort, complications such as disc disease in the spine, vascular fragility, gonadal failure, done density loss, chronic pain and musculoskeletal impairment appear at a much younger age. The information obtained from this study will not only help the treatment of effected patients, but will also provide insights into the pathological processes of normal aging.