NEW RECESSIVE SYNDROME CHARACTERIZED BY INCREASED CHROMOSOMAL BREAKAGE AND SEVERAL FINDINGS WHICH OVERLAP WITH FANCONI-ANEMIA

We describe four cases with several findings of Fanconi anemia (FA), b ut without hypersensitivity to DNA cross-linking that is the distingui shing characteristic of FA. Two of the cases are male and female sibs of Hispanic origin, age 6 years and 11 months, respectively. Both have short stature, failure to thrive, absent thumbs, short palpebral fiss ures, and skin pigmentation abnormalities. The girl also has developme ntal ''dysplasia'' of her hips. Presently, both siblings are hematolos cally normal. Elevated baseline chromosome breakage was observed in th e boy, but not in the girl. Neither sib showed elevated diepoxybutane (DEB)-induced chromosomal breakage. In a subsequent pregnancy, prenata l studies showed slightly elevated baseline and DEB induced chromosome breakage (greater than normal, but lower than the established range f or FA). The fetus had intrauterine growth retardation and an absent ri ght thumb. A review of cases referred to the International Fanconi Ane mia Registry for DEB testing showed one additional case with similar f indings. That patient, a girl, of Caucasian English ancestry, age 14 y ears, had short stature, a history of failure to thrive, skin pigmenta tion abnormalities, absent right thumb, hypoplastic left thumb, and hy drocephalus that resolved spontaneously. Elevated baseline chromosome breakage was observed in skin fibroblasts but not in lymphocytes. We p ostulate that these cases represent a previously undescribed autosomal recessive syndrome. These and other previously reported cases provide evidence for alternative genetic mechanisms that may result in develo pmental anomalies similar to those seen in FA. (C) 1998 Wiley-Liss, In c.