We describe four cases with several findings of
Fanconi anemia (FA), but without
hypersensitivity to
DNA cross-linking that is the distinguishing 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 fissures, and skin pigmentation abnormalities. The girl also has developmental "dysplasia" of her hips. Presently, both siblings are hematologically normal. Elevated baseline
chromosome breakage was observed in the boy, but not in the girl. Neither sib showed elevated
diepoxybutane (DEB)-induced
chromosomal breakage. In a subsequent pregnancy, prenatal studies showed slightly elevated baseline and DEB induced
chromosome breakage (greater than normal, but lower than the established range for FA). The fetus had
intrauterine growth retardation and an absent right thumb. A review of cases referred to the International
Fanconi Anemia Registry for DEB testing showed one additional case with similar findings. That patient, a girl, of Caucasian English ancestry, age 14 years, had short stature, a history of
failure to thrive, skin pigmentation abnormalities, absent right
thumb, hypoplastic left thumb, and
hydrocephalus that resolved spontaneously. Elevated baseline
chromosome breakage was observed in skin fibroblasts but not in lymphocytes. We postulate 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 developmental anomalies similar to those seen in FA.