Dyskeratosis Congenita: A Case Report

Dyskeratosis congenita (DC) is a rare genetic disease of telomere biology and is characterized by the classic triad of reticular skin pigmentation, dysplastic nails, and oral leukoplakia (4, 6,16). Autosomal dominant, autosomal recessive and X-linked recessive forms of the disease have been defined, and it is associated with the genes encoding telomerase and components of telomere-related proteins (12,15,17). The risk for progressive bone marrow failure, myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), solid tumors (especially squamous cell carcinomas of the head/neck or anogenital cancers) and pulmonary fibrosis is increased (1,3). To date, mutations in the DKC1 (X-linked), TERT (autosomal dominant or autosomal recessive), TERC and TINF2 (autosomal dominant), NHP2, CTC1, NOP 10 and WRAP53 (autosomal recessive) genes have been identified as causing DC (14). The most widely known genetic model is the X-linked recessive form, and it is associated with a missense mutation of the DKC1 gene. This gene encodes a nucleolar protein (dyskerin) that is essential for ribosome biogenesis and telomere maintenance (18). We present here the molecular and cl inical findings of a case of DC. In our case, a hemizygotic mutation in the DKC1 gene (c.227C>T, p.Ser76Leu) was detected.The 20-year-old male presented herein was born weighing 2100 gr as the second live birth of the second pregnancy of a 22-year-old mother. The boy did not have any hallmarks reported in his prenatal history. He had frequent infections. The boy, whose nails did not grow for approximately 10 years, had pigmentation anomalies in the skin for about the same period of time. The patient was diagnosed with splenomegaly 2 years ago. He had complaints of anemia, imperception and failure to gain weight for a long time. In his physical examination, he had blepharitis, tooth decay, microcephaly, sparse hair, moustache and beard, cachectic appearance and pes planus, in addition to a classical triad of symptoms: reticular, hyperpigmented skin lesions in the neck and shoulders, leukoplakia of the tongue, and dystrophy in the nails of the hands and feet (Fig. la-c). All of his hand fingerprints were absent. In the gastroscopic examination, he exhibited esophageal stenosis (web) at the cervical level and grade 3 esophageal varices in the distal esophagus. He exhibited pancytopenia in the complete blood count analysis and osteoporosis and osteopenia in the DEXA scan. Portal hypertension was observed in the portal vein Doppler US as well as periportal fibrosis in the liver, massive splenomegaly and ascites in the abdomen. His echocardiogram revealed normal cardiac function. His 42-year-old mother had prematurely gray hair and dystrophic toe nails. The case was assessed as DC due to these findings. The patient exhibited short telomeres and a hemizygotic mutation in the DKC1 gene (c.227C>T, p.Ser76Leu), and his mother had the same heterozygous mutation. No mutations were found in the father.Abnormal skin pigmentation, nail dystrophy, bone marrow failure and leukoplakia are among the major clinical characteristics of dyskeratosis congenita. Other well-defined somatic features include epiphora, learning disability/growth retardation/mental retardation, pulmonary disease, short stature, excessive tooth decay/tooth loss, esophageal stenosis, premature hair loss/prematurely gray hair/sparse eyebrow, malignancy, intrauterine growth retardation, liver disease/peptic ulcer/ enteropathy, ataxia/cerebellar hypoplasia, hypogonadism/undescended testes, microcephaly, urethral stenosis/phimosis, osteoporosis/aseptic necrosis/scoliosis and deafness. For a diagnosis of DC, the patient must have 2 or more of the 4 major features and 2 or more of the somatic features (7). Our case satisfied the diagnostic criteria of DC.The most commonly reported form of DC is the X-linked form. Mutations in the DKC1 gene result in DC cases of varying severity. While the children appear normal at birth, the classical triad of mucocutaneous lesions are observed in the first decade of life, bone marrow failure develops in the second decade of life, and death occurs due to bone marrow failure and complications of bleeding and infections in the third decade (2, 6). …