Mialou V, Leblanc T, Peffault de Latour R, Dalle J-H, Socié G
Institut d'hématologie et oncologie pédiatrique (IHOP), 1, place Professeur-J.-Renaut, 69008 Lyon, France.
Arch Pediatr. 2013 Mar;20(3):299-306. doi: 10.1016/j.arcped.2012.12.003. Epub 2013 Jan 23.
Dyskeratosis congenita is a rare inherited bone marrow failure characterized by excessively short telomeres in highly proliferative tissues. These abnormalities are due to disturbance of the telomere maintenance machinery. The clinical presentation is characterized by skin pigmentation, nail dystrophy, and mucosal leukoplakia. All these mucocutaneous features are rare in childhood: they usually appear between 5 and 10 years of age. In young children, the initial presentation can associate bone marrow failure and neurological or ocular problems: Hoyeraal-Hreidarsson and Revesz syndromes, respectively. Clinical progression of the disease can lead to aplastic anemia (86% of all patients) and to pulmonary or hepatic complications. These patients also have an increased risk of cancer. Diagnosis is often suspected on bone marrow failure with no clinical or biological abnormalities compatible with Fanconi anemia diagnosis. The telomere length study can be helpful for diagnosis in case of aplastic anemia in children before studying gene mutations. Until now, 6 genes (DKC1, TERT, TERC, NOLA2, NOLA3, TINF2) have been identified in dyskeratosis congenita. Transmission of the disease can be autosomal recessive, autosomal dominant, or X-linked. In half of the cases, the genetic abnormality is unknown. Treatment of DC has to be adapted to each patient, from symptomatic or androgenic treatment to hematopoietic stem cell transplantation.
先天性角化不良是一种罕见的遗传性骨髓衰竭,其特征是在高度增殖组织中的端粒过度缩短。这些异常是由于端粒维持机制紊乱所致。临床表现以皮肤色素沉着、指甲营养不良和黏膜白斑为特征。所有这些皮肤黏膜特征在儿童期都很罕见:它们通常在5至10岁之间出现。在幼儿中,最初表现可能分别伴有骨髓衰竭以及神经或眼部问题:即霍耶拉尔 - 赫雷达尔松综合征和雷维斯综合征。疾病的临床进展可导致再生障碍性贫血(占所有患者的86%)以及肺部或肝脏并发症。这些患者患癌症的风险也会增加。诊断通常是在出现骨髓衰竭且无符合范可尼贫血诊断的临床或生物学异常时怀疑。在研究基因突变之前,端粒长度研究对儿童再生障碍性贫血的诊断可能有帮助。到目前为止,已在先天性角化不良中鉴定出6个基因(DKC1、TERT、TERC、NOLA2、NOLA3、TINF2)。该疾病的遗传方式可以是常染色体隐性遗传、常染色体显性遗传或X连锁遗传。在一半的病例中,遗传异常尚不清楚。先天性角化不良的治疗必须根据每个患者的情况进行调整,从对症治疗或雄激素治疗到造血干细胞移植。