Jill and Mark Fishman Center for Lymphatic Disorders, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Eur J Hum Genet. 2022 Sep;30(9):1022-1028. doi: 10.1038/s41431-022-01123-9. Epub 2022 May 24.
Central conducting lymphatic anomaly (CCLA) is a heterogenous disorder caused by disruption of central lymphatic flow that may result in dilation or leakage of central lymphatic channels. There is also a paucity of known genetic diagnoses associated with CCLA. We hypothesized that specific genetic syndromes would have distinct lymphatic patterns and this would allow us to more precisely define CCLA. As a first step toward "precision lymphology", we defined the genetic conditions associated with CCLA by performing a retrospective cohort study. Individuals receiving care through the Jill and Mark Fishman Center for Lymphatic Disorders at the Children's Hospital of Philadelphia between 2016 and 2019 were included if they had a lymphangiogram and clinical genetic testing performed and consented to a clinical registry. In our cohort of 115 participants, 26% received a molecular diagnosis from standard genetic evaluation. The most common genetic etiologies were germline and mosaic RASopathies, chromosomal abnormalities including Trisomy 21 and 22q11.2 deletion syndrome, and PIEZO1-related lymphatic dysplasia. Next, we analyzed the dynamic contrast magnetic resonance lymphangiograms and found that individuals with germline and mosaic RASopathies, mosaic KRASopathies, PIEZO1-related lymphatic dysplasia, and Trisomy 21 had distinct central lymphatic flow phenotypes. Our research expands the genetic conditions associated with CCLA and genotype-lymphatic phenotype correlations. Future descriptions of CCLA should include both genotype (if known) and phenotype to provide more information about disease (gene-CCLA). This should be considered for updated classifications of CCLA by the International Society of Vascular Anomalies.
中央导水管淋巴异常（CCLA）是一种由中央淋巴流中断引起的异质性疾病，可能导致中央淋巴通道扩张或渗漏。与 CCLA 相关的已知遗传诊断也很少。我们假设，特定的遗传综合征会有不同的淋巴模式，这将使我们能够更精确地定义 CCLA。作为“精准淋巴学”的第一步，我们通过进行回顾性队列研究来确定与 CCLA 相关的遗传条件。如果在费城儿童医院的 Jill 和 Mark Fishman 淋巴疾病中心接受治疗的个体接受了淋巴管造影和临床遗传检测，并同意参加临床登记，他们将被纳入研究。在我们的 115 名参与者队列中，26%的人从标准遗传评估中获得了分子诊断。最常见的遗传病因是种系和嵌合 RAS 病、染色体异常包括 21 三体和 22q11.2 缺失综合征以及 PIEZO1 相关的淋巴管发育不良。接下来，我们分析了动态对比磁共振淋巴造影，发现种系和嵌合 RAS 病、嵌合 KRAS 病、PIEZO1 相关的淋巴管发育不良和 21 三体的个体具有独特的中央淋巴流表型。我们的研究扩大了与 CCLA 相关的遗传条件以及基因型-淋巴表型相关性。未来对 CCLA 的描述应包括基因型（如果已知）和表型，以提供有关疾病的更多信息（基因-CCLA）。这应被认为是对国际血管异常学会更新的 CCLA 分类的考虑因素。
