Uria-Oficialdegui M L, Navarro S, Murillo-Sanjuan L, Rodriguez-Vigil C, Benitez-Carbante M I, Blazquez-Goñi C, Salinas J A, Diaz-de-Heredia C
Pediatric Hematology and Oncology Division, Hospital Universitari Vall d´Hebron, Barcelona, Spain.
Pediatric Division, Hospital Universitario SonEspases, Palma de Mallorca, Spain.
Front Pediatr. 2023 Aug 1;11:1182476. doi: 10.3389/fped.2023.1182476. eCollection 2023.
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.
先天性角化不良（DC）是一种多系统的超罕见遗传病，其特征为体细胞受累、骨髓衰竭和易患癌症。本研究的主要目的是通过一组儿童期确诊并长期随访的患者来描述DC的自然病程。
对1998年至2020年间儿童期确诊后随访长达24年的患者进行多中心、回顾性、纵向研究。
14例患者在3至17岁（中位年龄8.5岁）被诊断为DC。诊断时均有血液学表现，9例在生命的第一个十年出现皮肤黏膜表现。7例表现为严重的DC变异型。随访期间均出现非血液学表现。12例患者检测到突变。13例在中位年龄8岁（范围3至18岁）进展为骨髓衰竭，8例接受了造血干细胞移植。中位随访时间为9年（范围2至24年）。6例患者死亡，中位年龄为13岁（范围6至24岁）。截至2022年11月，8例患者仍存活，中位年龄为18岁（范围6至32岁）。他们均未发生髓母细胞综合征或癌症。
在我们的系列研究中，DC与高发病率和高死亡率相关。血液学表现出现早且持续存在。非血液学表现逐渐发展。可能由于年龄较小，无患者发生癌症。由于疾病的复杂性，多学科随访和向成人护理的充分过渡至关重要。
