Cancer-prone syndrome of mosaic variegated aneuploidy and total premature chromatid separation: Report of five infants

Five infants (two girls and three boys) from four families all had severe p re- and postnatal growth retardation, profound developmental delay, microce phaly, hypoplasia of the brain with Dandy-Walker complex or other posterior fossa malformations, and developed uncontrollable clonic seizures. Four in fants developed Wilms tumors, and one showed cystic lesions in bilateral ki dneys. All five infants showed variegated mosaic aneuploidy in cultured lym phocytes. In two infants whose chromosomes were prepared by us, 48.5%-83.2% lymphocytes showed total premature chromatid separation (PCS). Their paren ts had 3.5%-41.7% of their lymphocytes in total PCS. The remaining three in fants and their parents, whose chromosomes were prepared at outside laborat ories, tended to show lower frequencies of total PCS. Another five infants reported with the disorder were reviewed together with the five infants we described. Together, their clinical and cytogenetic manifestations were sim ilar enough to suggest a syndrome. Seven of the 10 infants developed proven or probable Wilms tumors. The age at diagnosis of the tumors was younger t han usual at 2-16 months. The tumors were bilateral in four infants and uni lateral in three infants, and cystic changes were present in six infants. T wo infants developed botryoid rhabdomyosarcoma. The carriers of the syndrom e are thus liable to tumorigenesis. The possible role of mitotic checkpoint defects, proven in two infants with the syndrome (Matsuura et al. [2000: A m J Hum Genet 69:483-486]), was discussed in connection with tumor developm ent and progression. (C) 2001 Wiley-Liss Inc.