Unraveling the pathogenesis of Hoyeraal–Hreidarsson syndrome,a complex telomere biology disorder

Hoyeraal–Hreidarsson (HH) syndrome is a multisystem genetic disorder characterized by very short telomeres and considered a clinically severe variant of dyskeratosis congenita. The main cause of mortality, usually in early childhood, is bone marrow failure. Mutations in several telomere biology genes have been reported to cause HH in about 60% of the HH patients, but the genetic defects in the rest of the patients are still unknown. Understanding the aetiology of HH and its diverse manifestations is challenging because of the complexity of telomere biology and the multiple telomeric and non‐telomeric functions played by telomere‐associated proteins in processes such as telomere replication, telomere protection, DNA damage response and ribosome and spliceosome assembly. Here we review the known clinical complications, molecular defects and germline mutations associated with HH, and elucidate possible mechanistic explanations and remaining questions in our understanding of the disease.     

Dyskeratosis congenita with corneal limbal insufficiency

We describe a newly diagnosed Turkish adolescent female with Dyskeratosis congenita along with the novel ocular finding of corneal limbal insufficiency. Corneal limbal insufficiency was suggested to be a premature aging sign resulting from a deficiency in corneal stem cell activity, a biological process caused by underlying telomeric defect in this disease. Pediatr Blood Cancer 2009;53:95–97. © 2009 Wiley‐Liss, Inc.     

Dyskeratosis Congenita: A Case Report

Dyskeratosis congenita, an uncommon situation in females, is described in a 30-year-old woman. The expression of the disease was partial and was characterized by mottled pigmentation, nail dystrophy, palmoplantar keratoderma, and hyperhidrosis.     

Disseminated papular acantholytic dyskeratosis

We present two cases of elderly women with clinically atypical transient disseminated papular eruption, showing suprabasal epidermal clefts with dyskeratosis and acantholysis. The clinical picture did not correspond to either Darier's disease, Hailey's disease or Graver's acantholysis. In spite of clinical similarity the cases differed in course and outcome. Overlapping dyskeratosis and acantholysis varied in different specimens. The case with transient acantholytic lesions of short duration showed much more pronounced dyskeratosis than the other in which several relapses occurred in a 4-year period. Such cases defying classification belong to the heterogeneous group of papular acantholytic dyskeratosis. (c) 1998 Elsevier Science B.V. All rights reserved     

Dyskeratosis congenita associated with three malignancies

Dyskeratosis congenita is a rare inheritable disorder characterized by abnormalities of the skin, nails and oral mucosa. Aplastic anaemia resulting from bone marrow hypoplasia is a frequent cause of death. Squamous cell carcinoma developing from leukoplakia and visceral malignancies are other complications of the disease. We report here a case of dyskeratosis congenita in a man who developed three neoplasias of different systems over a period of many years. Squamous cell carcinoma and gastric adenocarcinoma manifested 17 years after the man was diagnosed with Hodgkin's disease.     

Genetic regulation of fetal haemoglobin in inherited bone marrow failure syndromes

Patients with inherited bone marrow failure syndromes (IBMFS) have ‘stress erythropoiesis’, with anaemia, macrocytosis, increased fetal haemoglobin (Hb F) and high erythropoietin levels. In haemoglobinopathies, Hb F levels are regulated by 3 quantitative trait loci, HBS1L‐MYB, BCL11A and Xmn1‐HBG2. In our study of 97 patients with an IBMFS, increased Hb F was associated with young age, male gender, anaemia, high erythropoietin levels, and alternative alleles in Xmn1‐HBG2 [adjusted P = 0·04 for the total group, driven by Fanconi anaemia (P = 0·02) and dyskeratosis congenita (P = 0·09)]. Thus Hb F is regulated in IBMFS by Xmn1‐HBG2, as it is in the haemoglobinopathies.