STUDIES OF MALFORMATION SYNDROMES OF MAN .29. WIEDEMANN-BECKWITH SYNDROME - CLINICAL, GENETIC AND PATHOGENETIC STUDIES OF 12 CASES

Twelve patients with the Wiedemann-Beckwith syndrome (WBS), including 6 familial cases from 2 families were described. The clinical manifestations do not allow for a differentiation between familial and sporadic cases. Consistent morphologic features include organomegaly, cytomegaly and nucleomegaly. The pathogenetic process may involve few or many organs and tissues and may represent a nuclear/mitotic dysfunction. Clinically, the manifestations are hyperplasia, hypoplasia, dysplasia, neoplasia and defects in differentiation. Secondary functional disturbances are sometimes prominent. The differential diagnosis of the WBS includes the Wilms'' tumor (WT)-aniridia syndrome; tumor-hypertrophy syndrome which includes WT, adrenocortical tumors or hepatoblastoma; the WT-pseudohermaphroditism syndrome and tumor-nevus syndrome, with or without malformations (particularly duplications) of the urinary tract. The latter 2 conditions are not associated with hemihypertrophy. Familial occurrence suggests that some cases of the WBS may be due to delayed mutation. Carriers of the premutated allele appear to belong to 2 classes: those with a high risk of producing affected offspring and those who transmit the premutated allele but have no affected offspring.