DC was first described by Zinsser in 1906. Later on it was subsequently described by Engman in 1926 and Cole in 1930. DC, which is also designated as Zinsser–Engman–Cole syndrome, is a triad consisting of nail dystrophy, mucosal leukoplakia and abnormal skin pigmentation.4
The precise incidence of DC is as yet unknown, however the prevalence has been estimated to be approximately 1 in 1 000 000.5
As per the English literature review, DC is an established multisystem disorder in which affected patients often present with haematological, ophthalmological, dermatological and neurological features with a marked tendency for spontaneous malignant transformation.6
Clinical features usually become evident by the age of 10 years. A reticular pattern of skin pigmentation develops first, followed by nail dystrophy. Intraorally, leukoplakic patches and progressive periodontal diseases are frequently observed.1
Patients with DC have a recognised increased risk of malignancy from pre-existing mucosal leukoplakia (hyperkeratosis), and the incidence of this transformation is in the order of approximately 35%, as compared to 1% in non-syndromic patients with tobacco-associated leukoplakia.7 8
The main causes of death include bone marrow failure/immunodeficiency (60% to 70% of cases), pulmonary complications (10% to 15%) and malignancies (5% to 10%).9
A brief compilation of the major clinical features is given in .
Clinical findings in dyskeratosis congenita
Clinically there appears to be three patterns of inheritance for DC: autosomal dominant (AD), autosomal recessive (AR) and X-linked recessive (XLR).10
Apart from these causes, sporadic cases of DC have also been reported.2
Among the inheritance causes, XLR is the most common mode of inheritance and thus results in a striking male predeliction.1
The presumed underlying defect in DC is an inability to preserve telomere length secondary to mutations in the genes for RNA or proteins composing this ribonucleoprotein complex. Chromosome ends are capped by telomeres, which are protective DNA–protein complexes. Telomeres shorten progressively with successive cell divisions in most cells, and cell division ceases when telomere length becomes critically short.6
Mutations in genes encoding the RNA template (telomerase RNA component; TERC), telomerase catalytic reverse transcriptase (TERT) and dyskerin, a component of the telomerase complex, have been identified in various DC families.9 11
The DKC1 gene is located on chromosome Xq28, which encodes the nucleolar protein dyskerin and has been reported to be associated with X-linked recessive DC. Mutations in TERC and TERT have been identified in some autosomal dominant DC, but in the majority of cases no mutations have been identified.10
An atypical form of DC, also known as Hoyeraal–Hreidarsson (HH) syndrome is a severe multisystem disorder that can present in neonatal period and infancy. It is characterised by severe growth retardation, immune deficiency, bone marrow failure and neurological abnormalities.9
Treatment of this syndrome revolves around the main causes of premature mortality such as malignancy and bone marrow failure. Early diagnosis of patients with DC will enable harvesting and storage of bone marrow before the onset of marrow failure in susceptible individuals. The current treatment for bone marrow failure is allogenic haemopoietic stem cell transplantation. It is extremely important to regularly screen for malignancies, especially of the gastrointestinal system. The management of oral malignancies is centred on regular review and biopsy of the premalignant hyperkeratotic lesions and surgical laser excision of any suspicious areas. Confirmed malignancies require prompt surgical resection and ipsilateral node clearance, with or without adjuvant radiotherapy. Regular medical and dental follow-up is of utmost importance.6
- Dyskeratosis congenita (DC) is a rare genodermatosis with fatal outcomes and a wide range of clinical manifestations that require appropriate attention and prompt treatment.
- Although onset may occur in early childhood, diagnosis is often delayed until clinical signs are apparent.
- Oral leukoplakic patches in DC have a higher malignant transformation rate, so any leukoplakic patch with or without history of tobacco consumption concomitant with the triad of features of DC should be dealt carefully.
- Early diagnosis can enable the patient to use the available treatment modalities to his or her best and thus reduce the associated morbidity and mortality.