Dyskeratosis congenita

Abstract

Dyskeratosis congenita (DC) is a genetic syndrome with progressive multisystem involvement classically characterized by the clinical triad of oral leukoplakia, nail dystrophy, and reticular hyperpigmentation. Frequent complications are bone marrow failure, increased rate of malignancy, lung and liver diseases. DC results from an anomalous progressive shortening of telomeres resulting in DNA replication problems inducing replicative senescence. We report a death due to DC in a 16-year-old male with bone marrow failure and multiple organ dysfunction. At autopsy, nail dystrophy and skin hypopigmentation were observed. Gross and microscopic examinations of the internal organs showed cardiac hypertrophy, multiple lung consolidations and prominent interstitial fibrosis, liver cirrhosis, and fibrosis. Multiple foci of extramedullary hematopoiesis were identified, including on the epidural surface of the dura, that is an infrequent location, mimicking a focal area of epidural hemorrhage. Only a few autopsy studies about DC are reported in the literature. Further research should be done to understand the pathophysiology of the disease and its complications.

Germline Variants and Characteristic Features of Hereditary Hematological Malignancy Syndrome

“…Traditionally, the distinction has been made based on the presence or absence of classical physical manifestations [ 213 ] such as abnormal nails, reticulate pigmentation of the skin, and oral leukoplakia in congenital dyskeratosis. Fanconi anemia (FA) [ 214 , 215 , 216 ], Diamond-Blackfan anemia (DBA) [ 217 , 218 , 219 ], dyskeratosis congenita (DC) [ 220 , 221 , 222 ], telomere biology disorders (TBDs) [ 223 ], and Schwachman-Diamond syndrome (SDS) [ 224 ] are well-known predisposing factors for MDS/AML and exhibit characteristic physical symptoms and signs.…”

“…DC/TBDs encompass genetically heterogeneous disorders associated with impaired telomere maintenance [ 220 , 221 , 222 , 223 ]. They are often associated with hematologic complications such as bone marrow failure, MDS, and AML.…”

Germline Variants and Characteristic Features of Hereditary Hematological Malignancy Syndrome

“…Traditionally, the distinction has been made based on the presence or absence of classical physical manifestations [146] such as abnormal nails, reticulate pigmentation of the skin, and oral leukoplakia in congenital dyskeratosis. Fanconi anemia (FA) [147][148][149], Diamond-Blackfan anemia (DBA) [150][151][152], dyskeratosis congenita (DC) [153][154][155] or telomere biology disorders (TBDs) [156], and Schwachman-Diamond syndrome (SDS) [157] are well-known predisposing factors for MDS/AML and exhibit characteristic physical symptoms and signs.…”

Oral Potentially Malignant Disorders: Etiology, Pathogenesis, and Transformation Into Oral Cancer

“…The inheritance of DC can be X-linked (Zinsser-Cole-Engleman syndrome), autosomal dominant (dyskeratosis congenita, Scoggins type), or autosomal recessive. In some cases, sporadic and mutational changes can also be associated with DC ( Gitto et al, 2020 ). A total of six genes related to the maintenance of telomerase structure and function have been identified to be mutated, and these are DKC1, TERC, TERT, TINF2, NOLA2, and NOLA3 ( Savage et al, 2009 ).…”

“…Oral symptoms include the appearance of white, thicker patches on the mouth’s mucous membranes (oral leukoplakia). These patches appear gradually, usually in the second, third, or fourth decade of life ( Gitto et al, 2020 ). Oral and dental abnormalities such as hypodontia, short blunted roots, hypocalcification, thin enamel, gingival recession, gingival inflammation with edema, gingival bleeding, alveolar bone loss, periodontitis, extensive caries, smooth atrophic tongue mucosa, leukoplakia, and lichen planus have been reported in DC (Elad, Aljitawi, Zadik).…”