The Wiedemann‐Beckwith syndrome: Pedigree studies on five families with evidence for autosomal dominant inheritance with variable expressivity

Abstract

We describe 18 individuals from five unrelated families with various manifestations of the Wiedemann-Beckwith syndrome. Pedigree analysis was performed on the 5 families and on another 19 families in the literature, each of which included more than one affected person. The following findings were obtained: 1) the clinical manifestations among the affected individuals were highly variable--those obvious in infancy tended to become less distinct with increasing age; 2) the syndrome was transmitted directly and vertically through three generations in four families, and through two generations in seven families; 3) male-to-male transmission was noted once; 4) the sex ratio in the affected individuals was not significantly different from 1; 5) the segregation ratio of the trait among the sibs of the probands was 0.571 +/- 0.066; 6) the affected + carrier/normal ratio was one among the offspring of the affected individuals and obligate carriers; 7) phenotrance (the expected presence of the trait in a generation) of the syndrome in the sibship of probands was complete, whereas that in earlier generations appeared low. The discrepancy is attributable to the lessening of the clinical features with increasing age as well as to a possibly less aggressive search for abnormalities in older generations. These findings indicate that the syndrome is an autosomal dominant trait with variable expressivity. High-resolution chromosome banding analysis in seven affected individuals and their respective parents showed no abnormalities.

Mouse mutant embryos overexpressing IGF-II exhibit phenotypic features of the Beckwith–Wiedemann and Simpson–Golabi–Behmel syndromes

“…Statistical and regression analyses of growth curve Data were compiled from original reports or reviews of nonoverlapping cases of BWS (Filipi and McKusick 1970;Sotelo-Avila and Singer 1970;Thorburn et al 1970;Kosseff et al 1976;Greenwood et al 1977;Shapiro et al 1982;McManamny and Barnett 1985;Niikawa et al 1986;Pettenati et al 1986;Takayama et al 1986;Takato et al 1989;Weng et al 1995b;Martínez y Martínez 1996) and SGBS (Simpson et al 1975;Behmel et al 1984Behmel et al , 1988Golabi and Rosen 1984;Opitz 1984;Tsukahara et al 1984;Neri et al 1988;Opitz et al 1988;Kö nig et al 1991;Garganta and Bodurtha 1992;Gurrieri et al 1992;Hughes-Benzie et al 1992a, 1996Chen et al 1993;Yamashita et al 1995). The frequency of occurrence of each manifestation (number of patients exhibiting a clinical feature as a fraction of total examined) is only indicative because of incomplete records.…”

Beckwith-Wiedemann Syndrome: Growth Pattern and Tumor Risk according to Molecular Mechanism, and Guidelines for Tumor Surveillance

“…However, data for adult height are inconclusive because of lack of information due to the discontinuation of follow-up after the usual period of surveillance for the occurrence of tumors. Several studies have reported patients in small cohorts to have a final height in the normal range [8,9,10,11], whereas others have reported adult heights exceeding +2 SDS [12,13,14,15,16,17,18] (table 1). …”

Beckwith-Wiedemann Syndrome: Difficulties with Prenatal Diagnosis

“…As children with BWS have a high risk for intra abdominal malignancies, especially Wilms' tu mor, hepatoblastoma, and neuroblastoma, fre quent sonogiaphical controls are necessary [5], Thegenetical background of BWS appears to be a mutation located on 11 p 15.5 [6]. In most familial cases, autosomal dominant in heritance with incomplete penetrance and variable expressivity was suggested [3,7], Some patients had structural anomalies of 1 lp [8], partly due to parental balanced trans locations [9]. The first prenatal diagnosis of BWS by ultrasound was performed in 1980 [10].…”