Pf. Giampietro et al., NEW RECESSIVE SYNDROME CHARACTERIZED BY INCREASED CHROMOSOMAL BREAKAGE AND SEVERAL FINDINGS WHICH OVERLAP WITH FANCONI-ANEMIA, American journal of medical genetics, 78(1), 1998, pp. 70-75
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.