Changes in skin pigmentation (reticulated
hypopigmentation and hyperpigmentation) often in combination with
telangiectases are more pronounced on the flexures of the big joints, neck,
and axillae, and along the inner thigh. Nail dystrophy is progressive and
initially may result in longitudinal ridges and finally in complete loss of
nails. The hair may be affected, leading to baldness. Leukoplakia most often
occurs in the mouth but also may affect other mucosal sites (e.g.,
esophagus, vagina, anus, urethral meatus, and lacrimal duct resulting in
strictures with dysphagia, dyspareunia, dysuria, and epiphora) and is
associated with an increased risk for malignancies (most often squamous cell
carcinoma). In male patients, testes often are undescended and hypoplastic.
Dental abnormalities (extensive cavities, premature loss) and increased
fragility of the bones caused by abnormal metaphyseal trabeculation and
osteoporosis have been reported. Lacrimal duct stenosis or atresia is
present in up to 80% of patients and leads to continuous epiphora. Up to
90% of patients suffer from bone marrow failure; rarely the diagnosis of
aplastic anemia precedes the diagnosis of dyskeratosis congenita. Some
patients develop myelodysplasia and acute myeloid leukemia. Pancytopenia
or complications related to bone marrow transplant (high rate of pulmonary
complications) are responsible for approximately 70% of the premature
deaths in this population. Approximately 20% of these patients show
pulmonary changes with progressive pulmonary fibrosis and restrictive lung
disease, arteriovenous shunting with microvascular changes, and reduced
diffusion capacity. It has been hypothesized that these underlying changes
are, at least in part, responsible for the high rate of pulmonary
complications in association with bone marrow transplant. Liver cirrhosis
with a nutmeg aspect may be present, and mucosal ulcerations may cause
gastrointestinal hemorrhage. Elevated immunoglobulin levels and increased
risk of opportunistic infections have been reported. Additional findings
(each in approximately 15-20% of patients) include prenatal and
postnatal growth retardation and mild-to-moderate mental retardation
(intracerebral calcifications) associated with mainly deafness-related
learning difficulties. In general, female patients tend to have a milder
course of the disease; nevertheless, bone marrow failure with death has been
reported.