Fanconi's anemia/pancytopenia (& TAR, Schwachman-Diamond,
Diamond-Blackfan, Poland
Syndrome, Bloom Syndrome, Dyskeratosis Congenita)
- (as oppsed to Fanconi Syndrome)
- Autosomal recessive; various chromosomal abnormalities present; chromosome
breaks due to abnormal DNA repair
- Anemia and skeletal/other congenital anomalies;
no thumb
- 80% of patients who have Fanconi anemia
exhibit congenital anomalies.
- Recognizing these anomalies is important
because the aplastic anemia usually is
not evident until 4 to 14 years of age (mean onset is 8 years). Pancytopenia at
birth is unusual. Tendency to leukemia.
- Among the anomalies are
-
hyperpigmentation (60%)
-
short stature (57%)
-
upper limb anomalies (48%) that
include
- absent, hypoplastic, supernumerary, or
bifid thumb (Fanconi can't
hitchhike - look like seal hand)
- aplasia of the first metacarpal or the
radius
-
hypogonadism (40%),
renal
abnormalities (complete absence of one kidney, hypoplasia, horsehoe kidney,
double ureters.
-
microcephaly (27%), mental
retardation, BL mild hearing loss
- Almost 20% of affected patients manifest
a variety of other skeletal anomalies.
- The only
potential cure is bone marrow transplantation
- early diagnosis allows for better donor
identification and patient preparation
- It is also important to make the diagnosis
to enable parents to use prenatal diagnosis for future children.
- Several complementation groups have been
identified with Fanconi anemia, with type A accounting for almost 66% of
cases.
- If the specific complementation groups can
be identified in the index case, DNA analysis can be used for prenatal
diagnosis.
- If a specific DNA defect is not
identified, increased chromosomal breakage in peripheral blood lymphocytes in
the presence of cross-linking agents can be used.
Several other disorders are associated with
skeletal anomalies and hematologic disease.
- Fanconi's Anemia (no thumb or
radius)
-
Schwachman-Diamond Syndrome
(pancreas)
- Dyskeratosis Congenita
(skin and nail changes)
- TAR syndrome (thrombocytopenia, absent
radius, thumbs present)
-
Diamond-Blackfan Anemia
(RBC hypoplasia)
- Bloom syndrome (predisp to leukemia, malignancies)
- Other rare disorders associated with both
skeletal anomalies and hematologic disorders include
- familial aplastic anemia syndromes
- cartilage-hair hypoplasia
- Dubowitz syndrome
- Seckel syndrome
-
Poland anomaly
- Acquired disorders also may be associated
with both hematologic and
skeletal abnormalities. Children who have newly diagnosed acute lymphoblastic
leukemia often present with bone pain and generalized radiologic signs, but
they do not have congenital abnormalities.
References:
Alter BP, Young NS. The bone marrow failure syndromes. In: Nathan DG,
Orkin SH, Oski FA, Ginsburg D, eds. Nathan and Oski's Hematology of
Infancy and Childhood. 5th ed. Philadelphia, Pa: WB Saunders Co; 1998:
286-301
Freedman MH. Inherited forms of bone marrow failure. In: Hoffman R,
Benz EJ Jr, Shattil SJ, et al, eds. Hematology: Basic Principles and
Practice. 3rd ed. New York, NY: Churchill Livingstone; 2000:260-297