Dyskeratosis congenita: beyond the triad and beyond the cause

Dyskeratosis congenita (DC) is a rare genodermatosis caused by mutations in various genes encoding the proteins responsible for maintaining the telomere length. It is defined by the presence of three clinical features: nail dystrophy, abnormal skin pigmentation, and oral leukoplakia. We herein report a typical case of DC with all three classical features along with pancytopenia, osteopenia, and epiphora but with no identifiable pathogenic mutations of DC-associated genes. Cutaneous examination revealed areas of hypopigmented and hyperpigmented macules forming a reticular pattern all over the body but mainly over the neck and upper chest, with relative sparing of the face. Skin atrophy with hypopigmentation was observed on the knuckles. The nails showed dystrophy in the form of pterygium, anonychia, and brittleness. The palms showed mild wrinkling with hypopigmented macules. Examination of the oral cavity revealed a white non-removable coating over the tongue and bilateral buccal mucosae (oral leukoplakia); the teeth were normal. Syringing of both eyes was performed by an ophthalmologist, and the patient was diagnosed with punctual stenosis (occlusion of the opening of the lacrimal canaliculus). DC is a genodermatosis caused by germline mutations in genes encoding telomerase-associated components, shelterin proteins, and other regulators of telomere length and replication. Depending upon the gene involved, the mode of inheritance can be X-linked autosomal dominant or autosomal recessive. DC is characterized by the clinical triad of abnormal skin pigmentation, dystrophic nails, and oral leukoplakia. Patients with DC are also known to develop other rare clinical features at later stages, including epiphora, early graying of the hair, premature tooth loss, enteropathy with malabsorption, immune deficiency, esophageal stricture, cardiomyopathy, liver cirrhosis, osteoporosis and avascular necrosis of the bone. Patients with DC are predisposed to the development of malignancies, especially hematological malignancies and head/neck cancer. Management of DC involves a multidisciplinary approach and includes genetic counseling of family members at risk, regular surveillance of the patient for bone marrow failure and malignancies, and treatment of the associated features and any complications. Dyskeratosis congenita (DC) is a rare genodermatosis caused by mutations in various genes encoding telomerase complex. We present a typical case of DC with all three classical features but with no pathogenic mutations of existing DC-associated genes thus raising the possibility of new unidentified genes in the pathogenesis of DC.