Dyskeratosis Congenita Clinical Presentation

Updated: Jan 27, 2020
  • Author: David T Robles, MD, PhD, FAAD; Chief Editor: William D James, MD  more...
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The mucocutaneous features of dyskeratosis congenita (DKC) typically develop between ages 5 and 15 years. The median age of onset of the peripheral cytopenia is 10 years.


Physical Examination

The triad of reticulated hyperpigmentation of the skin, nail dystrophy, and leukoplakia characterizes dyskeratosis congenita (DKC). The syndrome is clinically heterogeneous; in addition to the diagnostic mucocutaneous features and bone marrow failure, affected individuals can have a variety of other clinical features.

The minimum requirement to diagnose DKC is the presence of 2 of 4 major features of the mucocutaneous triad and bone marrow failure 2 or more of the other somatic symptoms. Late diagnosis leads to inappropriate treatment and increased mortality/morbidity. [3]

Cutaneous findings

The primary finding is abnormal skin pigmentation, with tan-to-gray hyperpigmented or hypopigmented macules and patches in a mottled or reticulated pattern. Reticulated pigmentation occurs in approximately 90% of patients. Poikilodermatous changes with atrophy and telangiectasia are common. The cutaneous presentation may clinically and histologically resemble graft versus host disease. The typical distribution involves the sun-exposed areas, including the upper trunk, neck, and face.

Other cutaneous findings may include alopecia of the scalp, eyebrows, and eyelashes; premature graying of the hair; hyperhidrosis; hyperkeratosis of the palms and soles; and adermatoglyphia (loss of dermal ridges on fingers and toes).

Nail findings

Nail dystrophy is seen in approximately 90% of patients, with fingernail involvement often preceding toenail involvement. Progressive nail dystrophy begins with ridging and longitudinal splitting. Progressive atrophy, thinning, pterygium, and distortion eventuate in small, rudimentary, or absent nails.

Mucosal findings

Mucosal leukoplakia occurs in approximately 80% of patients and typically involves the buccal mucosa, tongue, and oropharynx. The leukoplakia may become verrucous, and ulceration may occur. Patients also may have an increased prevalence and severity of periodontal disease.

Other mucosal sites may be involved (eg, esophagus, urethral meatus, glans penis, lacrimal duct, conjunctiva, vagina, anus). Constriction and stenosis can occur at these sites, with subsequent development of dysphagia, dysuria, phimosis, and epiphora.

Hematological findings (bone marrow failure)

Approximately 90% of patients have peripheral cytopenia of one or more lineages, with a median age of onset of 10 years. This is the initial presentation in some cases, especially in cryptic variants of DKC, where (pan-)cytopenia is also the most frequent clinical manifestation. [43] Bone marrow failure is a major cause of death, with approximately 70% of deaths related to bleeding and opportunistic infections as a result of bone marrow failure.

Pulmonary complications

Approximately 20% of individuals with DKC develop pulmonary complications, including pulmonary fibrosis and abnormalities of pulmonary vasculature. [44] The recommendation is that DKC patients avoid taking drugs with pulmonary toxicity (eg, busulfan) and that they have their lungs shielded from radiation during BMT.

Increased risk of malignancy

Patients have an increased prevalence of malignant mucosal neoplasms, particularly squamous cell carcinoma of the mouth, nasopharynx, [45] esophagus, rectum, vagina, or cervix. These often occur within sites of leukoplakia. The prevalence of squamous cell carcinoma of the skin is also increased. Other malignancies reported include Hodgkin lymphoma, adenocarcinoma of the gastrointestinal tract, and bronchial and laryngeal carcinoma. Malignancy tends to develop in the third decade of life.

Neurologic system findings

Patients may have learning difficulties and mental retardation.

Ophthalmic system findings

DKC reportedly is associated with retinal vasculopathy, [25, 46] conjunctivitis, blepharitides, pterygium, proliferative retinopathy, frosted branch angiitis, [47] sparse eyelashes, ectropion, entropion, and trichiasis. [4] Lacrimal duct stenosis resulting in epiphora (ie, excessive tearing) occurs in approximately 80% of patients. Exudative retinopathy is a common presentation of Coats disease or familial exudative vitreoretinopathy, but DKC should also be considered in such cases. [48] Retinitis caused by CMV, an opportunistic pathogen commonly found among immunocompromised patients, is also a possible clinical feature of DKC. [49]

Dental findings

DKC may also present with multiple dental changes, including caries, periodontal disease, and taurodontism. [4]

Skeletal system findings

Patients may have mandibular hypoplasia, osteoporosis, avascular necrosis, and scoliosis.

Gastrointestinal system findings

These may include esophageal webs, posterior pharyngeal wall squamous cell carcinoma, hepatic angiosarcoma, [50] hepatosplenomegaly, cirrhosis, [51]  and diffuse mesangial sclerosis (and subsequent end-stage renal disease) in one pediatric case. [52]

Genitourinary system findings

Hypospastic testes, hypospadias, and ureteral stenosis are reported.

Female carriers

Female carries of DKC may have subtle clinical features. One study showed that 3 of 20 female carriers had clinical features that included a single dystrophic nail, a patch of hypopigmentation, or mild leukoplakia.

Immunological defects

Decreased B cells, decreased natural killer (NK) cells, and dysgammaglobulinemia result in frequent infections. Immune defects are commonly found in conjunction with other DKC symptoms, but they have also been found to precede these symptoms. [14]  There has also been an association with hypothyroidism and hypogonadism. [53]