Mucosal and skin pigmentation with abnormal nails

A 6-year-old boy presented with reticulated hyperpigmentation on the eyelids and upper helix since birth (Figures 1 and 2). Nail dystrophy of the fingernails and toenails had developed over the past 3 years, consisting of deformity, atrophy, distal destruction, and onychoschizia (Figure 3). Hyperpigmented patches on the tongue and mild leukokeratosis had been present for 1 year, (Figure 4). Dermoscopy of the hyperpigmented lesions on the eyelids and ears revealed pigmented lines consisting of brown dots and globules arranged in a reticulated pattern. No abnormal pigmentation was observed on the neck, trunk, or extremities. Blood cell counts and routine serum chemistries examinations were within normal limits. Dyskeratosis congenita. Whole-exome sequencing (WES) was carried out in the proband, which revealed a genetic variant in the DKC1 gene (NM_001363.5: c.1174A>G; p.M392V) on the X chromosome. Sanger sequencing confirmed the presence of this variant in the patient, as well as in his asymptomatic mother and younger sister in heterozygosis. According to the interpretation standards and guidelines of the American College of Medical Genetics and Genomics (ACMG), the identified variant was classified as a variant of uncertain clinical significance, supported by the PM2 and PM3 criteria. The patient's father did not carry the variant. A patient's maternal uncle displayed mental retardation and experienced a gradual development of hyperpigmentation on his facial at the age of 4. He was diagnosed with leukaemia at the age of 14 and died of liver ascites at the age of 16. Dyskeratosis congenita (DKC, Zinsser-Engman-Cole syndrome) is a rare inherited multisystemic disease characterized by reticular pigmentation, nail dystrophy, and oral leukoplakia.1 Several genes have been identified as responsible for DKC, including DKC1, TINF2, TERC, TERT, C16orf57, NOLA2, NOLA3, WRAP53/TCAB1, and RTEL1.2 DKC1 is the most common pathogenic gene of DKC, and causes recessive X-linked DKC.3 Dyskerin, the protein encoded by the DKC1 gene, is directly involved in maintaining the telomere length.4 Telomeres are specialized nucleoprotein structures at the ends of chromosomes that are essential for chromosomes structure and stability.5 The clinical presentation of DKC may involve multiple organ systems, including the skin, eyes, lungs, liver, and bone marrow. The classic diagnostic triad of DKC is reticular skin pigmentation, nail dystrophy, and mucosal leukoplakia.6 The morbidity rates of skin pigmentation, nail dystrophy, and mucosal leukoplakia are 90%, 88%, and 80%, respectively.2 Reticular skin pigmentation usually occurs in the first decade of life on sun-exposedareas, including the neck, trunk, and both extremities.7 Major nail changes include longitudinal ridges, onychoschizia, pterygium, and anonychia, which may occur from the first few months of life through adolescence.2 Mucosal leukoplakia may manifest as white or black patches at birth or within the first few months of life8 and has a high risk of malignant transformation. In our patient, the reticulated hyperpigmentation of the face, nail dystrophy, and black patches on the tongue were suspicious of DKC. Other disorders with nail dysplasia and reticulated hyperpigmentation should be considered in the differential diagnosis. These include Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis; however, these diseases are mainly caused by autosomal dominant variants in the keratin 14 gene. On the other hand, Fanconi anaemia usually presents with diffuse pigmentary abnormalities, and pancytopenia appears earlier. Dermoscopic changes in hyperpigmented DKC lesions9, 10 consist of pigmented lines arranged in a reticulated pattern. Granular grey‒brown pigmented structures are diffusely distributed in a pepper-like pattern within the pigmented lines. DKC features important multisystemic manifestations. Patients with DKC are vulnerable to several life-threatening conditions, including aplastic anaemia, leukaemia, pulmonary fibrosis, and cancers (especially cancers of the head, neck, or genitals). DKC affected individuals are also prone to abnormalities of internal organs, such as narrow tear ducts, dental problems, osteoporosis, and avascular necrosis of the hip and shoulder joints, among others. Fengming Chen wrote the manuscript and performed the practical work. Ling Liu collected and analysed patients' data. Pingshen Fan edited the manuscript. All authors contributed to the article and approved the submitted version. The authors declare no funding was received for this study. The authors declare no conflict of interest. This study was approved by the Xijing Hospital medical ethics committees and conducted according to the Declaration of Helsinki. Written informed consent was obtained from the minor(s)' legal guardian for the publication of any potentially identifiable images or data included in this article. The data that support the findings of this study are available from the corresponding author upon reasonable request.