A new overgrowth syndrome with accelerated skeletal maturation, unusual facies, and camptodactyly

Weaver, David D.; Graham, C. Benjamin; Thomas, I. T.; Smith, David W.

doi:10.1016/s0022-3476(74)80675-x

Cited by 163 publications

(92 citation statements)

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“…11,41 In Childhood overgrowth in NF1 microdeletions M Spiegel et al their facial appearance, the patients COS, PFA (Figure 2), and ERS closely resemble this overlapping NF1-Weaver-like phenotype. As determined by FISH analysis, all three patients have the common 1.4 Mb spanning deletion type I.…”

Section: Discussionmentioning

confidence: 81%

“…10 Weaver syndrome, first reported in 1974, is characterized by overgrowth in childhood (both height and occipitofrontal head circumference (OFC) above the 97th centile), markedly advanced carpal bone age, developmental delay, and distinctive facial appearance. 11 The genetic basis of this mostly sporadic syndrome has not been completely elucidated. Although Douglas et al (2003) and Rio et al (2003) found NSD1 mutations in a group of patients with a diagnosis of Weaver syndrome, NSD1 mutations could not be detected in other Weaver syndrome patients.…”

Section: Introductionmentioning

confidence: 99%

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Childhood overgrowth in patients with common NF1 microdeletions

et al. 2005

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While growth retardation and short stature are well-known features of patients with classical neurofibromatosis type 1 (NF1), we found advanced height growth and accelerated carpal bone age in patients with an NF1 microdeletion. Our analysis is based on growth data of 21 patients with common 1.4/1.2 Mb microdeletions, including three patients with a Weaver-like appearance. Overgrowth was most evident in preschool children (2-6 years, n ¼ 10, P ¼ 0.02). We conclude that childhood overgrowth is part of the phenotypic spectrum in patients with the common 1.4/1.2 Mb NF1 microdeletions and assume that the chromosomal region comprised by the microdeletions contains a gene whose haploinsufficiency causes overgrowth.

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Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Childhood overgrowth in patients with common NF1 microdeletions

et al. 2005

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“…3B), and humerus (Fig. 3C) (Weaver et al, 1974). In the literature, two Japanese patients with Weaver like syndrome were reported (Shimura et al, 1979;Tsukahara et al, 1984).…”

Section: Kondo Et Almentioning

confidence: 92%

“…Since Weaver et al (1974) first described two patients with overgrowth and unusual facies, 28 patients with the Weaver syndrome have been reported (Weaver, 1990;Moreno and Kirkland, 1974;Bosch-Banyeras et al, 1978;Shimura et al, 1979;Gemme et al, 1980;Majewski et al, 1981;Weisswichert et al, 1981;Meinecke et al, 1983;Jalaguier, 1983;Roussounis and Crawford, 1983;Amir et al, 1984;Farrell and Hughes, 1985;Ardinger et aI., 1986;Greenberg et al, 1989). However, clinical manifestations of some patients including a Japanese were similar to those of other overgrowth syndromes such as Marshall-Smith and Beckwith-Wiedemann syndromes (Shimura et al, 1979;Menguy et al, 1986;Pattenati et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

A Japanese male infant with the weaver syndrome

1990

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“…Alterations in the expression of enhancer of zeste homolog 2 (EZH2) and matrix metalloproteinase-2 (MMP2) were detected in ACHN-BO5 cells. EZH2 is involved in maintaining the transcriptional repressive state in cells and mutation of EZH2 causes Weaver syndrome (10), a congenital disorder associated with rapid growth beginning in the prenatal period, resulting in a characteristic facial appearance and certain skeletal features (11). In addition, studies have demonstrated that altered EZH2 expression promotes human cancer development (12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Alterations in enhancer of zeste homolog 2, matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 expression are associated with ex vivo and in vitro bone metastasis in renal cell carcinoma

Wang

Ren

Guo

et al. 2015

Molecular Medicine Reports

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Abstract. Renal cell carcinoma (RCC) has a high potential for bone metastasis; however, the molecular mechanisms underlying this metastasis have remained to be elucidated. The present study aimed to explore the expression levels of enhancer of zeste homolog 2 (EZH2), matrix metalloproteinase-2 (MMP2) and tissue inhibitor of metalloproteinase-2 (TIMP2) as determinants of RCC-associated bone metastasis. Their expression was evaluated in a newly generated RCC cell subline that has a high potential for bone metastasis, in tissue specimens from metastasized bone tissues from patients with RCC and in RCC tissues without metastasis. A total of 25 RCC tissue specimens without metastasis and 13 RCC tissue specimens with bone metastasis were acquired for immunohistochemical analysis of EZH2, MMP2 and TIMP2 protein expression. The expression levels of EZH2, MMP2 and TIMP2 mRNA and protein were analyzed in the ACHN and ACHN-BO5 cell lines using western blot and reverse transcription polymerase chain reaction (PCR) analyses. Methylation-specific PCR was also used to analyze TIMP2 promoter methylation. EZH2 and MMP2 proteins were found to be expressed at higher levels in tissues from patients where RCC had metastasized to the bone as compared with those in RCC patients without metastasis, whereas there was no significant difference in the expression of TIMP2 protein between the two tissues. Furthermore, the expression of EZH2 protein was correlated with MMP2 expression, but there was no significant correlation between the expression of EZH2 and TIMP2 proteins. The in vitro results using cell lines confirmed the ex vivo findings, indicating that the expression levels of EZH2 and MMP2 protein and mRNA were higher in ACHN-BO5 cells than those in ACHN cells. By contrast, TIMP2 protein and mRNA expression levels were lower in ACHN-BO5 cells than those in the parental ACHN cells. The TIMP2 promoter was highly methylated in ACHN-BO5 cells compared with that in ACHN cells. Upregulation of EZH2, MMP2 and TIMP2 expression was correlated with metastasis of RCC to bone tissues ex vivo and in vitro. Further studies are required in order to elucidate the mechanism underlying the altered expression of these genes. IntroductionRenal cell carcinoma (RCC), which has been suggested to originate from the renal tubules and collecting tube epithelial cells, accounts for 85% of malignant kidney neoplasms and ~2% of all human malignancies (1,2). RCC is a pathologically heterogeneous disease, which can be classified into clear, papillary, granular, spindle and mixed cell subtypes based on certain cytoplasmic features (3). RCC morbidity increases by 2% annually and mortality has reached ~100,000 cases/year worldwide (4). Approximately 30% of patients with RCC develop metastatic disease, most frequently in the lungs, bones or brain (5). A clinical study confirmed that osteolysis represented 30% of the total metastatic disease cases associated with RCC (6). The incidence rate of bone tissue metastasis was higher in autopsy data from patients with RCC (5...

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A new overgrowth syndrome with accelerated skeletal maturation, unusual facies, and camptodactyly

Cited by 163 publications

References 10 publications

Childhood overgrowth in patients with common NF1 microdeletions

Childhood overgrowth in patients with common NF1 microdeletions

A Japanese male infant with the weaver syndrome

Alterations in enhancer of zeste homolog 2, matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 expression are associated with ex vivo and in vitro bone metastasis in renal cell carcinoma

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