Blood, 1 May 2002, Vol. 99, No. 9, pp. 3081-3082
Moyamoya and stroke in sickle cell anemia: bad news
and good news
If having unannounced painful crises that present with the
quality of giant toothaches was not enough, some sickle cell anemia patients are also affected by devastating strokes. Dobson et al (page
3144) have examined a subgroup among the sickle stroke victims: those
with moyamoya. Moyamoya in Japanese means a cloud or puff of
smoke, an apt name since the diagnostic images in the brain are an
ethereal lace of small vessels. Dobson et al's paper brings bad news:
this condition in sickle cell anemia patients doubles the chances for
recurrent cerebral vascular events. The other side of the coin is that
this condition has high frequency in Japan, where familial
moyamoya disease has been described and the gene responsible has been
traced by Yamauchi et al (Stroke 2000;31:930-935) to chromosome
17q25, and multipoint linkage analysis also has indicated that
the disease gene is contained within the 9-cM region of D17S785 to
D17S836. Hence the cloning of this gene might occur in the near future.
Is this good news for some sickle cell anemia patients? No doubt.
Because only a small percentage of sickle cell anemia patients have
this complication, it is another example of the
multigenic origin of the phenotype, while the
basic genetic abnormality, the capacity of deoxyHbS to polymerize, is
the monogenic event: the sickle globin mutation. So for a
sickle cell anemia patient to express moyamoya the patient
needs to carry, in addition to the 
S gene, a
further genetic predisposition (traditionally called epistatasis,
epistatic genes, or more recently, modifier genes). It is conceivable
that the same gene (or a related gene) found in the Japanese familial
form of moyamoya is involved. Nevertheless, it is bound to be a
different mutational event interacting with the pleiotropic effects
found in sickle cell patients. The cloning of the Japanese gene will
allow the search of polymorphisms of this relevant gene (or genes) that
might, if we are lucky, suggest therapeutic interventions or, at a
minimum, permit for an early diagnosis of the risk and, hence,
potential approaches for stopping its progression We are living in
interesting times, a mixed blessing no doubt.
Ronald L. Nagel
Albert Einstein College of Medicine
