Beckwith‐Wiedemann Syndrome and Hemihyperplasia

Abstract

Beckwith-Wiedemann syndrome, characterized by the triad of omphalocele, macroglossia, and gigantism, has a population incidence estimated at 1/13,700. This is likely an underestimate, because individuals with milder phenotypes may not be diagnosed. Some cases of isolated hemihyperplasia may, in fact, represent Beckwith-Wiedemann syndrome with reduced expressivity. Additional clinical features of Beckwith-Wiedemann syndrome include hemihyperplasia, umbilical hernia, diastasis recti, embryonal tumors, cytomegaly of the fetal adrenal cortex, ear anomalies, visceromegaly, renal abnormalities, and neonatal hypoglycemia. Supportivefindings may include polyhydramnios and prematurity, enlarged placenta, cardiomegaly, and characteristic facies. The latter feature is much more recognizable in early life and becomes less obvious over time. Beckwith-Wiedemann syndrome is a complex multigenic disorder caused by a variety of genomic and epigenomic alterations affecting the expression of growth regulatory genes on chromosome 1 l p l 5 .

Tumour surveillance in Beckwith–Wiedemann syndrome and hemihyperplasia: A critical review of the evidence and suggested guidelines for local practice

“…Additional clinical risk factors include the presence of hemihyperplasia, nephromegaly, nephrogenic rests or nephroblastomatosis 4,11 , 21 . More recently several studies have provided evidence that tumour risk also varies according to the specific molecular cause of BWS 7,20 , 22–24 . A meta‐analysis of these studies indicates that there is a strong association between loss of imprinting of the H19 gene and the development of cancer, in particular Wilms tumour (13 tumours in 35 patients; 37%) 20 .…”

“…Various surveillance protocols for Wilms tumour and hepatoblastoma have been proposed previously 4–7 . It is our practice to screen children with BWS and IHH using abdominal ultrasound focusing on the liver, kidneys and adrenals every 3 months until the age of 8 years, and a serum AFP measurement every 3 months until the age of 4 years (Table 2).…”

“…Various surveillance protocols have been proposed with the aim of reducing the morbidity and mortality from cancer in children with BWS and IHH, 4–7 although there is currently limited evidence to support their efficacy. In order to assess the utility of surveillance it is necessary to understand the magnitude of the tumour risk and the utility of surveillance modalities.…”

Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings

“…[2][3][4][5][6][7][8][9][10][11][12], PEG1/MEST (7q32), KCNQ1OT1 and H19 (both 11p15.5), DLK1 (14q32), SNRPN (15q11-12), PEG3 (19q13), and NESPAS (20q13) by methylation-specific PCR (MS-PCR) following bisulphite treatment, as previously described. 1,3,5 Primer sequences for NESPAS were derived from Williamson et al 6 Aberrant results were confirmed by either pyrosequencing 7 or MS-PCR with another primer set.…”

Transgenerational Epigenetics and Brain Disorders

“…Because of these epigenetically mediated allele-specific gene expressions, imprinted genes are believed to be especially susceptible to epigenetic dysregulation by environmental factors, such as nutrition, stress, and toxic agents. Furthermore, it is suggested that certain inherited brain disorders such as Beckwith-Wiedemann syndrome, Rett syndrome, fragile X syndrome, and Angelman's syndrome arise from abnormal-specific imprinted genes (Kaminsky, Wang, & Petronis, 2006;Kantor, Shemer, & Razin, 2006;Weksberg, Shuman, & Smith, 2005). When these imprinting aberrations occur during early fetal development, they are often manifested as developmental and neurological disorders.…”