Beckwith-Wiedemann syndrome. Clinical and etiopathogenic aspects of a model genomic imprinting entity

Abstract

The Beckwith-Wiedemann syndrome is the most common genetic entity in overgrowth, with an approximate incidence of 1 in 10 00013 700births. Its broad clinical spectrum includes pre- and postnatal macrosomia, macroglossia, pinna abnormalities, abdominal wall defects, visceromegaly, and hyperinsulinemic hypoglycemia. This syndrome predisposes to childhood cancer and is caused by diverse genetic and/or epigenetic disorders that usually affect the regulation of genes imprinted on chromosome 11p15.5. The knowledge of (epi) genotype-phenotype correlations has prompted recommendations to propose different health care strategies, including tumor surveillance protocols based on molecular classification, aimed at standardizing clinical practice. The objective of this article is to describe the current status of the Beckwith-Wiedemann syndrome, a model of genomic imprinting.

Fibroepithelial Breast Tumors in a Teenager with Beckwith-Wiedemann Syndrome: A Case Report and Review of Literature

“…The diagnosis is based on molecular tests or clinical signs. However, in children with features of BWS who do not fulfill clinical diagnostic criteria, the molecular tests may play an important role in diagnosis (2,5). Our patient had BWS with a positive family history and characteristic right hemihypertrophy.…”

“…The condition was named after American pediatric pathologist John Bruce Beckwith in 1963, and German pediatrician Hans-Rudolf Wiedemann in 1964, reported the syndrome independently (4). This syndrome is caused by diverse genetic and epigenetic disorders that usually affect the regulation of genes imprinted on chromosome 11p15.5 (2). It presents with a wide and varied clinical spectrum, including hemihyperplasia, macroglossia, prominent eyes with infraorbital creases, facial nevus flammeus, and midfacial hypoplasia, but the BWS facies often normalizes across childhood.…”

“…Such incidence may be underestimated in mild phenotypes and most likely increases due to a positive correlation with assisted reproductive techniques. This syndrome is caused by diverse genetic and epigenetic disorders that usually affect the regulation of genes imprinted on chromosome 11p15.5 (2). The relevant imprinted chromosomal region in 11p15.5 and uniparental disomy (UPD) of chromosome 11p15 is a risk factor for BWS-associated tumorigenicity.…”

Hypoglycaemia in endocrine, diabetic, and internal diseases [Hipoglikemia w schorzeniach endokrynologicznych, diabetologicznych i internistycznych]

“…Among the genetically conditioned syndromes in which hyperinsulinaemic hypoglycaemia is a symptom is Beckwith-Wiedemann syndrome. It is a rare group of congenital disorders characterised by pre-and post-natal macrosomia, macroglossia, irregularities in the construction of the earlobes, abdominal wall defects, and an increased predisposition to embryonic cancers [44].…”

“…Spośród genetycznie uwarunkowanych zespołów, w których objawem jest hipoglikemia hiperinsulinemiczna, jest zespół Beckwitha-Wiedemanna. Jest to rzadki zespół wad wrodzonych, charakteryzujący się przed-i pourodzeniową makrosomią, makroglosią, nieprawidłowościami w budowie małżowin usznych, wadami powłok brzucha oraz zwiększoną predyspozycją do nowotworów embrionalnych [44].…”