PEDIATRICS Vol. 105 No. 3 March 2000, p. e39

ELECTRONIC ARTICLE:
A Syndrome Involving Intrauterine Growth Retardation, Microcephaly, Cerebellar Hypoplasia, B Lymphocyte Deficiency, and Progressive Pancytopenia

Received Jun 29, 1999; accepted Nov 5, 1999.

Patrick Revy^*, Meinrad Busslinger, Kei Tashiro^§, Fernando Arenzana, Pascal Pillet^¶, Alain Fischer^*, and Anne Durandy^*

From the ^* INSERM U429, Hôpital Necker-Enfants-Malades, Paris;  Research Institute of Molecular Biology, Vienna, Austria; ^§ Center for Molecular Biology and Genetics, Kyoto University, Sakyo-Ku, Kyoto, Japan;  Institut Pasteur, Paris, France; and ^¶ CHU de Bordeaux, France.

We report a new complex syndrome involving profound failure to thrive with severe intrauterine growth retardation, cerebellar abnormalities, microcephaly, a complete lack of B lymphocyte development, and secondary, progressive marrow aplasia. B cell differentiation was found to be blocked at the pro-B cell stage. Although not strictly proven, a genetic origin is likely, according to similar cases reported in the literature.

Three candidate genes, PAX5, encoding B cell-specific activator protein, a factor involved in B cell lineage commitment, stromal cell-derived factor 1, and CXCR4, encoding a chemokine and its receptor, respectively, were thought to be responsible for this disease, given the similarity between the phenotype of the corresponding knock-out mice and the clinical features of the patient. However, the genomic DNA sequences of these 3 genes were normal, and normal amounts of stromal cell-derived factor 1 and CXCR4 were present.

These data strongly suggest that another molecule is involved in early B cell differentiation, hematopoiesis, and cerebellar development in humans.

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