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Chapter 29 Inherited Bone Marrow Failure Syndromes 367

Fig. 29.4 DYSTROPHIC NAILS IN DYSKERATOSIS CONGENITA.

multiple separate primaries in different sites involving the tongue and
nasopharynx. Thus the sites of most of the cancers involve areas
known to be abnormal in DC, such as mucous membranes and the
gastrointestinal tract.

Differential Diagnosis

Several physical findings can be used to distinguish FA from DC. The
following abnormalities are seen only in DC and not FA: nail dys-
trophy, leukoplakia, abnormalities of the teeth, hyperhidrosis of the
palms and soles, and hair loss. Specific presentations of DC may have
prominent overlap with other syndromes. The Hoyeraal-Hreidarsson
syndrome variant of DC and the Revesz syndrome variant of DC
are two examples. The ataxia–pancytopenia syndrome at least in
some families is a variant of DC with mutations in TINF2. The
spectrum of manifestations in Coats plus syndrome may lead to
investigative workup towards inherited eye disorders and degenerative
brain disease, but screening for DC by telomere length should be
considered.

Natural History and Prognosis

In classical DC, nail dystrophy and skin pigmentation present first,
Fig. 29.5 LEUKOPLAKIA OF THE TONGUE IN DYSKERATOSIS often in the first 10 years of life. BM failure usually follows in the
CONGENITA. teenage years and twenties. The primary causes of death are hemor-
rhage secondary to thrombocytopenia or intestinal vascular anomalies,
pulmonary fibrosis, sepsis from severe neutropenia, and complica-
tions after HSCT. In the patients who develop cancer or MDS/AML,
of MDS/AML in DC is much lower than in FA. At the age of 50 the disease or its treatment can prove fatal. Pulmonary fibrosis can
years, the cumulative risk of solid cancers and MDS/AML is estimated develop in 20% of cases and is typically progressive and culminates
as 40% and 3%, respectively. Most of the cancers are squamous cell in death caused by respiratory failure. Considerable clinical hetero-
carcinomas or adenocarcinomas, and the oropharynx and gastro- geneity exists even within the same family, and some patients live into
intestinal tract are involved most frequently. Some patients have their forties with only moderate nail changes and mild cytopenias.