遗传性皮肤角化异常症（Dyskeratosis congenita，DC）是一种罕见的多系统遗传性疾病，特征为体内受累、骨髓衰竭和易患癌症。本研究的主要目的是通过对一组儿童诊断DC并长期随访的患者队列描述DC的自然病程。本研究为多中心、回顾性、纵向研究，纳入了自1998年至2020年间在儿童期被诊断的患者，随访时长长达24年。其中14名患者在3岁至17岁之间被诊断为DC（中位数为8.5岁）。在诊断时所有患者均有血液学表现，其中9名患者在第一个十年出现黏膜皮肤症状。7例患者表现为严重的DC变异型。在随访期间，所有患者均出现了非血液学表现。12名患者的基因突变已被确认。其中13名患者在中位年龄8岁时（范围3-18岁）发展为骨髓衰竭，其中8例接受了造血干细胞移植。中位随访时间为9年（范围2-24年）。6名患者死亡，中位年龄为13岁（范围6-24岁）。至2022年11月，仍有8名患者活着，中位年龄为18岁（范围6-32岁）。其中没有发生骨髓母细胞性综合征或癌症。在我们的系列中，DC与高发病率和高死亡率相关。血液学表现早期出现且持续存在，非血液学表现逐渐发展。由于患者年龄较小，没有患者发生癌症。鉴于该疾病的复杂性，多学科随访和合适的转归至成年护理至关重要。 © 2023 Uria-Oficialdegui, Navarro, Murillo-Sanjuan, Rodriguez-Vigil, Benitez-Carbante, Blazquez-Goñi, Salinas and Diaz-de-Heredia.

Dyskeratosis congenita (DC) is a multisystem and ultra-rare hereditary disease characterized by somatic involvement, bone marrow failure, and predisposition to cancer. The main objective of this study is to describe the natural history of DC through a cohort of patients diagnosed in childhood and followed up for a long period of time.Multicenter, retrospective, longitudinal study conducted in patients followed up to 24 years since being diagnosed in childhood (between 1998 and 2020).Fourteen patients were diagnosed with DC between the ages of 3 and 17 years (median, 8.5 years). They all had hematologic manifestations at diagnosis, and nine developed mucocutaneous manifestations during the first decade of life. Seven presented severe DC variants. All developed non-hematologic manifestations during follow-up. Mutations were identified in 12 patients. Thirteen progressed to bone marrow failure at a median age of 8 years [range, 3-18 years], and eight received a hematopoietic stem cell transplant. Median follow-up time was 9 years [range, 2-24 years]. Six patients died, the median age was 13 years [range, 6-24 years]. As of November 2022, eight patients were still alive, with a median age of 18 years [range, 6-32 years]. None of them have developed myeloblastic syndrome or cancer.DC was associated with high morbidity and mortality in our series. Hematologic manifestations appeared early and consistently. Non-hematologic manifestations developed progressively. No patient developed cancer possibly due to their young age. Due to the complexity of the disease multidisciplinary follow-up and adequate transition to adult care are essential.© 2023 Uria-Oficialdegui, Navarro, Murillo-Sanjuan, Rodriguez-Vigil, Benitez-Carbante, Blazquez-Goñi, Salinas and Diaz-de-Heredia.