Dyskeratosis congenita
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]
Synonyms and keywords: Zinsser-Cole-Engman syndrome; X-linked dyskeratosis congenita; Cole-Rauschkolb-Toomey syndrome; DKCX
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Dyskeratosis Congenita from other Diseases
Epidemiology and Demographics
Age: The mucocutaneous features of DKC typically develop between ages 5 and 15 years. The median age of onset of the peripheral cytopenia is 10 years.
Gender: The male-to-female ratio is approximately 3:1.
Natural history, Complications and Prognosis
Complications include:
- Conjunctivitis, blepharitides, lacrimal duct stenosis, and pterygium
- Mandibular hypoplasia, osteoporosis, avascular necrosis, and scoliosis.
- Cirrhosis
- Bone marrow failure - infections, bleeding
- Pulmonary fibrosis
- Dysphagia, dysuria, phimosis, and epiphora - due to constriction and stenosis can occur at the sites of leukoplakia
- Increased risk of malignancy - increased prevalence of malignant mucosal neoplasms, particularly squamous cell carcinoma of the mouth, nasopharynx, esophagus, rectum, vagina, or cervix. These often occur within sites of leukoplakia. The prevalence of squamous cell carcinoma of the skin is also increased.
- Death - due to infections, bleeding
Prognosis of the disease is poor with a mean survival of 30 years. Prognosis is worse for X-linked and autosomal recessive forms compared to autosomal dominant form.
Diagnosis
Symptoms
Patients with DKC complain of
- Cutaneous pigmentation - hyper or hypo-pigmentation
- Premature graying of hair
- Dystrophy of the nails - ridging and longitudinal splitting
- Leukoplakia of the oral mucosa (patches on the tongue and inside the mouth)
- Continuous/excess lacrimation (due to atresia of the lacrimal ducts)
- Decreased libido (due to testicular atrophy in the male carriers).
Physical Examination
The triad of reticulated hyperpigmentation of the skin, nail dystrophy, and leukoplakia characterizes 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.
Skin:
- Abnormal skin pigmentation - 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.
- Alopecia of the scalp, eyebrows, and eyelashes
- Premature graying of the hair
- Hyperhidrosis
- Hyperkeratosis of the palms and soles
- Adermatoglyphia (loss of dermal ridges on fingers and toes).
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.
Extremities:
- Nail dystrophy (ridging and longitudinal splitting) - seen in approximately 90% of patients, with fingernail involvement often preceding toenail involvement.
- Absent nails - in advanced disease.
Mucosal findings:
- Mucosal leukoplakia - occurs in approximately 80% of patients and typically involves the buccal mucosa, tongue, and oropharynx.
Patients also may have an increased prevalence and severity of periodontal disease. Other mucosal sites may be involved (e.g., esophagus, urethral meatus, glans penis, lacrimal duct, conjunctiva, vagina, anus).
Respiratory:
- Rales are heard in those having pulmonary fibrosis.
Neurologic:
- Low IQ
- Patients may have learning difficulties and mental retardation.
Eye:
Abdomen:
Genitourinary system findings::
- Hypospastic testes (small testis),
- Hypospadias
- Ureteral stenosis
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.
Lab tests
- Complete blood counts and differential counts
- Stool tests for occult blood
- Pulmonary function tests
X-ray
- X-ray head shows calcification of basal ganglia
- Chest x-ray for pulmonary fibrosis
Treatment
Recent research has used induced pluripotent stem cells to study the disease mechanisms in humans, and discovered that the repgrogramming of somatic cells restores telomere elongation in dyskeratosis congenita cells despite the genetic lesions that affect telomerase. The reprogrammed DC cells were able to overcome a critical limitation in TERC (Telomerase RNA component) levels and restored function (telomere maintenance and self-renewal). Therapeutically, methods aimed at increasing TERC expression could prove beneficial in DC patients. [1]
References
- ↑ Agarwal; et al. (2010). ": Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients". Nature. 464: 292–296. doi:10.1038/nature08792. PMID 20164838.
External links
- GeneReviews/NCBI/NIH/UW entry on Dyskeratosis Congenita
- Dyskeratosis Congenita research study of Inherited Bone Marrow Failure Syndromes (IBMFS)
Template:Congenital malformations and deformations of integument Template:X-linked disorders