Disease characterized by the combination of congenital
neurologic anomalies and late-onset bone marrow hypoplasia.
Only two cases have been
described. Inheritance could be autosomal recessive. Chromosome studies were
normal and did not show increased fragility.
Diagnosis is clinical based on the presence of
neurologic anomalies combined with easy bruising. Diagnosis is confirmed by
CT or MRI scans of the brain, complete blood count (nonmegaloblastic
macrocytosis), and bone marrow biopsy that reveals hypocellular bone marrow
with erythroid hyperplasia, reduced granulopoiesis, and quasi-absence of
The main feature of this syndrome is the late
appearance (around age 4 years) of easy bruising with purpuric lesions and
scattered petechiae as a result of a low platelet count. In addition,
patients may present with acute bleeding as a consequence of minor trauma,
which, in turn, leads to anemia. The other characteristic of this syndrome
is the presence of neurologic anomalies, which seem to be quite variable
(hemiparesis with dilated left ventricle and asymmetry of the peduncles,
partial agenesis of the corpus callosum, hydrocephalus, Dandy-Walker
syndrome, developmental delay, and seizures). Congenital ocular anomalies
include strabismus, optic nerve hypoplasia, and rotary nystagmus. No
skeletal anomalies have been described in association with this syndrome.
The disorder usually is not responsive to steroid therapy. Bone marrow
transplant seems to be the only therapeutic solution.
Obtain a complete blood count and
consult a hematologist if necessary. Ensure that blood products are readily
available before going to the operating room.
In the presence of bone marrow aplasia,
it may be wise to avoid neuraxial anesthesia and the placement of central
lines via the subclavian route. Good padding for positioning is advised. To
decrease the formation of petechiae or bruises, less-frequent cycling of the
blood pressure cuff is recommended if the patient is stable or when an
arterial line is in place. Use sterile technique for catheter insertion
because these patients may also be neutropenic.
In order to not further compromise
hemostasis, drugs that inhibit thromboxane A2 synthesis (e.g.,
acetylsalicylate, nonsteroidal antiinflammatory drugs) or otherwise
interfere with hemostasis should be avoided or used with caution only.
Acetaminophen, although less potent, should be preferred instead.
Blackfan-Diamond Syndrome: Congenital hypoplastic anemia that
manifests in the first year of life and has an increased risk for leukemia.
Fanconi Anemia: Inherited anemia leading to bone marrow failure,
myelogenous leukemia, and, in older patients, many cancers (head and neck,
esophageal, gastrointestinal, vulvar, and anal).
Drachtman R, Weinblatt M, Sitarz A, et al: Marrow hypoplasia associated
with congenital neurologic anomalies in two siblings. Acta Paediatr Scand