Dyskeratosis congenita (DKC) is a rare congenital disorder that results from defects in telomere maintenance due to mutations in genes coding for proteins that participate in telomere maintenance. It is a progressive disease with a highly variable phenotype, making diagnosis difficult. The disease is characterized by the classic triad of abnormal skin pigmentation, nail dystrophy, and oral leukoplakia (white patches in the mouth) (Figure 1) but these symptoms might not always manifest in patients (Dokal, 2000; Fernández García and Teruya-Feldstein, 2014; Kirwan and Dokal, 2009). Other symptoms include thrombocytopenia, anemia and testicular atrophy(Fernández García and Teruya-Feldstein, 2014). Patients with DKC often age prematurely and have
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Treatment typically focuses on treating the symptoms that have manifested in each individual patient. Patients are advised to avoid activities that could put them at even higher risks for cancer such as avoiding smoking, alcohol and excessive sun exposure. Some patients with bone marrow failure respond well to androgens and hematopoietic growth hormones. Androgens such as oxymetholone can increase red blood cell counts(Dokal et al., 2011; Khincha et al., 2014). Granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) can also be used to help increase the production of certain white blood cells (neutrophils)(Dokal et al., 2011). These treatments are only temporary, however(Dokal et al., 2011; Khincha et al., 2014). Hematopoietic stem cell transplantation can cure or ameliorate some of the blood abnormalities caused by DKC, especially in patients with bone marrow failure. However, this treatment will not affect the tissue damage caused by DKC(Sakaguchi et al., 2013). Additionally, fatal pulmonary complications as a result of this transplantation are common. Patients with DKC have a higher sensitivity towards radiation and chemotherapy drugs so treatment of cancer is difficult. For this reason, alternative treatments for cancer must be used (such as surgical resection of cancers)(Marsh et al., 1992). Recent research on induced pluripotent stem cells has found that DKC cells can be “reprogrammed” to restore telomerase function. This could have applications to stem cell therapy in DKC patients(Agarwal et al., 2010). Additionally, researchers at Penn State have found a link between the Wnt molecular signaling cascade and telomere maintenance. A positive feedback loop exicst between Wnt signaling and expression of proteins that cap and protect telomeres. This research could have applications in the development of therapies in DKC patients that stimulate this feedback loop(Woo et al.,
Treatment typically focuses on treating the symptoms that have manifested in each individual patient. Patients are advised to avoid activities that could put them at even higher risks for cancer such as avoiding smoking, alcohol and excessive sun exposure. Some patients with bone marrow failure respond well to androgens and hematopoietic growth hormones. Androgens such as oxymetholone can increase red blood cell counts(Dokal et al., 2011; Khincha et al., 2014). Granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) can also be used to help increase the production of certain white blood cells (neutrophils)(Dokal et al., 2011). These treatments are only temporary, however(Dokal et al., 2011; Khincha et al., 2014). Hematopoietic stem cell transplantation can cure or ameliorate some of the blood abnormalities caused by DKC, especially in patients with bone marrow failure. However, this treatment will not affect the tissue damage caused by DKC(Sakaguchi et al., 2013). Additionally, fatal pulmonary complications as a result of this transplantation are common. Patients with DKC have a higher sensitivity towards radiation and chemotherapy drugs so treatment of cancer is difficult. For this reason, alternative treatments for cancer must be used (such as surgical resection of cancers)(Marsh et al., 1992). Recent research on induced pluripotent stem cells has found that DKC cells can be “reprogrammed” to restore telomerase function. This could have applications to stem cell therapy in DKC patients(Agarwal et al., 2010). Additionally, researchers at Penn State have found a link between the Wnt molecular signaling cascade and telomere maintenance. A positive feedback loop exicst between Wnt signaling and expression of proteins that cap and protect telomeres. This research could have applications in the development of therapies in DKC patients that stimulate this feedback loop(Woo et al.,