Hagon-Nicod Olivia, Fellmann Florence, Novy Jan, Lebon Sébastien, Wider Christian, Lazor Romain, Bonny Olivier
Department of Medicine, Service of Internal Medicine, Fribourg State Hospital, Fribourg, Switzerland.
The Collaboratory, University of Lausanne, Lausanne, Switzerland.
Front Med (Lausanne). 2024 Dec 12;11:1513619. doi: 10.3389/fmed.2024.1513619. eCollection 2024.
Tuberous sclerosis complex (TSC) is a genetic and multisystemic disorder that affects between 1/6'000 and 1/10'000 of newborns. Clinical criteria and/or genetic analysis establish the diagnosis. The mechanistic target of rapamycin (mTOR) inhibitors everolimus or sirolimus reduce the severity of several TSC-related clinical traits. We report here on the epidemiology and management of TSC patients in a large Swiss canton: the canton of Vaud.
We extracted patient files containing the diagnostic code TSC in 2015 at the Lausanne University hospital (tertiary reference center for a population of about 755'000 people) and in specialized neurological institutions of the same region.
We identified 52 patients with a diagnosis of TSC. The majority of the patients with a pathologic result in genetic testing were positive for a pathogenic variant in the gene, including five cases of contiguous gene deletion syndrome of and causing both polycystic kidney disease and TSC. The most frequent clinical manifestations encountered were affecting the skin (87% of patients), the brain (83%), the heart (46%) and the kidneys (46%). Neuropsychiatric disorders were described in 56% of cases. At the time of data collection (2015), there were 2 patients using systemic mTOR inhibitors and 16 patients using topical mTOR inhibitors for dermatological features. Next, we compared this data with those of large published cohorts. While we found fewer cases than expected for the screened population, demographic as well as genetic data were overall similar to the literature. However, we observed that some clinical manifestations (renal, lung and neuropsychiatric disorders) were less frequently described in our cohort.
This work indicates that TSC and some of its clinical manifestations is under-reported. It raises concern that patients with mild manifestations are often not referred to reference centers with dedicated multidisciplinary group. The follow-up by expert board is instrumental in offering systematic screening of all putatively affected organs and to assess the eligibility for targeted treatment.
结节性硬化症（TSC）是一种遗传性多系统疾病，在新生儿中的发病率为1/6000至1/10000。通过临床标准和/或基因分析进行诊断。雷帕霉素（mTOR）抑制剂依维莫司或西罗莫司可减轻多种与TSC相关的临床特征的严重程度。我们在此报告瑞士一个大州——沃州TSC患者的流行病学情况及治疗情况。
我们提取了2015年洛桑大学医院（约75.5万人口的三级参考中心）以及同一地区专门的神经机构中包含诊断代码TSC的患者档案。
我们确定了52例TSC诊断患者。基因检测结果为病理性的大多数患者在该基因中存在致病变异，其中包括5例因基因和基因的连续性缺失综合征导致多囊肾病和TSC的病例。最常见的临床表现为皮肤受累（87%的患者）、大脑受累（83%）、心脏受累（46%）和肾脏受累（46%）。56%的病例有神经精神障碍的描述。在数据收集时（2015年），有2例患者使用全身性mTOR抑制剂，16例患者因皮肤症状使用局部mTOR抑制剂。接下来，我们将这些数据与已发表的大型队列研究数据进行了比较。虽然我们发现筛查人群中的病例数比预期少，但人口统计学和基因数据总体上与文献相似。然而，我们观察到我们队列中一些临床表现（肾脏、肺部和神经精神障碍）的描述较少。
这项研究表明TSC及其一些临床表现报告不足。令人担忧的是，症状较轻的患者往往未被转诊至设有专门多学科团队的参考中心。专家委员会的随访有助于对所有可能受累的器官进行系统筛查，并评估靶向治疗的适用性。
