Disorders of sex development

Disorders of sex development (DSD) occur in 1–2/10,000 live births, with a specific molecular diagnosis only possible in 20% of cases. Presentation is usually at birth, and gender assignment must be avoided before review by an expert multidisciplinary team. Initial investigations allow a working diagnosis to be made within 48 hr. In 46,XY DSD, surgery may be necessary to correct hypospadias, reposition or remove undescended testes, and remove symptomatic Müllerian remnants. In 46,XX DSD, feminizing surgery is performed less frequently than in the past, but genitoplasty may still be indicated. Psychosocial support is required to promote positive adaptation as gender dissatisfaction can occur in certain conditions. Long-term outcome data are sparse.     

Loss of function,missense, and intronic variants in NOTCH1 confer different risks for left ventricular outflow tract obstructive heart defects in two European cohorts

Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes.     

Factors Affecting Recurrent Deep Vein Thrombosis after Pharmacomechanical Thrombolysis and Left Iliac Vein Stent Placement in Patients with Iliac Vein Compression Syndrome

PurposeThis study evaluated the factors affecting contralateral and ipsilateral recurrent deep vein thrombosis (DVT) after iliac vein stent placement in patients with iliac vein compression syndrome (IVCS).Materials and MethodsData from 130 patients (95 female patients) who underwent catheter-directed thrombolysis and stent placement for IVCS with left lower leg thrombosis at a single institution were retrospectively analyzed. Mean patient age was 69.0 ± 14.0 years old. Median follow-up was 14 months (range, 3–164 months). Anticoagulation therapy was prescribed for 6 months, followed by lifelong antiplatelet therapy. Multivariate logistic regression analysis was performed to evaluate the factors affecting the development of contralateral and ipsilateral recurrent DVT.ResultsSeven patients (5.4%) developed contralateral DVT (median, 26 months; range, 2–61 months), and 11 patients (8.5%) developed ipsilateral DVT (median, 1 month; range, 0–53 months). Stent location (odds ratio [OR], 11.564; 95% confidence interval [CI], 1.159–115.417) and in-stent thrombosis during follow-up (OR, 15.142; 95% CI, 1.406–163.119) were predictors of recurrent contralateral DVT. Thrombophilia (OR, 47.560; 95% CI, 2.369–954.711), remaining inferior vena cava filter (OR, 30.552; 95% CI, 3.495–267.122), and in-stent thrombosis during follow-up (OR, 82.057; 95% CI, 2.915–2309.848) were predictors of ipsilateral DVT.ConclusionsContralateral DVT occurs late and is associated with extension of the iliac vein stent to the inferior vena cava and in-stent thrombosis. Ipsilateral DVT occurs relatively early and is associated with thrombophilia, remaining inferior vena cava filter, and in-stent thrombosis.     

Oral Everolimus for Treatment of a Giant Left Ventricular Rhabdomyoma in a Neonate—Rapid Tumor Regression Documented by Real Time 3D Echocardiography

The presented case reports on successful treatment with everolimus in a neonate with left ventricular giant rhabdomyoma. The authors used a different dosage regime compared to literature and documented rapid tumor regression by 3D echocardiography.     

以肺动脉高压为首发表现的先天性中枢性低通气综合征临床特征和基因分析

目的探讨先天性中枢性低通气综合征(CCHS)的临床和基因变异特征。方法分析1例首发表现为不明原因肺动脉高压的CCHS患儿的临床资料,并总结国内外文献中CCHS病例的临床特点、致病机制和基因变异情况。结果11月龄女婴,主要表现为浮肿、尿少、低血压、嗜睡、发绀、抽搐及颅内压增高。B型脑利钠肽、丙氨酸氨基转移酶升高,凝血酶原时间延长。颅脑磁共振示右侧额叶出血;超声心动图示中重度肺动脉高压。靶向捕获二代测序未发现可能的致病基因。采用Sanger法验证示患儿PHOX 2 B基因第3外显子存在多聚丙氨酸重复扩展变异,基因型为20/25。患儿入院后采用无创通气,睡眠时呼吸浅慢、微弱,伴血氧下降;血气分析提示二氧化碳潴留。随后改用夜间无创通气、降肺压药物治疗。复查肺动脉压力明显下降,生命体征稳定。随访至24月龄,夜间只需较低压力水平的无创通气,生长发育无异常。结论对于不明原因的肺动脉高压伴撤机困难患儿,需警惕CCHS。疑诊者应尽早针对CCHS相关基因进行靶向捕获二代测序及PHOX 2 B基因Sanger法验证。早期给予无创通气有望改善预后。     

心血管造影在复杂和(或)复合先天性心脏病诊断中的应用

目的 探讨心血管造影在先天性心脏病（简称先心病）复杂和（或）复合畸形中的应用价值。方法 分析360例复杂和（或）复合畸形造影所见及其与超声心动图等临床检查的联系。结果 本组360例（包括75例肺动脉闭锁合并室间隔缺损、62例右室双出口、60例法乐四联症、52例单心室、42例大动脉错位、15例三尖闭锁、6例冠状动脉异常、5例完整型肺静脉畸形连接、5例完全型心内膜垫缺损、4例共同动脉干、3例室间完整的肺动脉闭锁、7例其他病例和24例外科术后检查）心血管造影和超声对比，纠正后者误、漏诊分别为34、30例及对合并畸形误诊16例。对复杂和（或）复合畸形中体肺侧支血管、冠状动脉畸形和肺动脉段分支及其异常的检测和诊断优于超声心动图，并可测量肺动、静脉压力及体肺侧支血管压力而优于其他影像学检查方法。结论 对于先心病复杂和（或）复合畸形的疑难病例诊断和鉴别诊断，尤其显示体、肺及冠状动脉分支的全貌及相关病变，以及测量肺动脉和心室压力等，心血管造影（含DSA）仍有重要或不可替代的作用。     

中老年男性下尿路症状的流行病学调查

为了了解下尿路症状在中、老年男性中的流行情况，用附加了二个症状问题的ＳＬ问卷对８７１名５２～７４岁的男子作回顾性调查，对调查结果作了年龄分组分析。结果发现：平均ＩＰＳＳ总分为４．９３分，无症状者为１２．２％，轻症者为６４．７％，中度症状者为１９．６％，重症者为３．５％。夜尿者占７２．３％，尿终滴沥占５４．４％，而症状中分值＞３分者尿终滴沥占２５．６％，夜尿占１４．６％，平均ＱＯＬ为１．７４，ＱＯＬ为０～２、３、４～６的比例分别为５２．７％、４６．０％、１．３％。ＱＯＬ与ＩＰＳＳ的相关性较好（ｒ＝０．６２），与梗阻症状群的相关性（ｒ＝０．５７）优于与刺激症状的相关性（ｒ＝０．４４）。中重度症状者中有７２．０％的人未进行治疗。