Beckwith-Wiedemann syndrome

Beckwith–Wiedemann syndrome (abbreviated BWS, EMG syndrome, in English Beckwith–Wiedemann syndrome), also referred to as EMG syndrome (based on the key features: Exomphalos, Macroglossia, Gigantism), is a genetic disorder characterized by an increased risk of tumor development, excessive growth, and congenital malformations. The cause of the disorder is abnormal gene regulation (dysregulation) involving the IGF2 growth factor gene, which is inherited from the father, and the H19 gene, which is inherited from the mother. This unregulated growth factor leads to increased growth (gigantism) and increases the risk of tumor formation. The disorder occurs sporadically in approximately 85% of cases, while 15% show familial transmission.

The syndrome is named after Dr. Hans‑Rudolf Wiedemann, who first described the association between omphalocele (a congenital defect of the abdominal wall characterized by herniation of the intestine), macroglossia (enlarged tongue), and gigantism (increased size of distal body parts such as the legs, arms, nose, etc.). Later, additional features were described by Professor John Beckwith, who identified enlargement of the adrenal glands in individuals with the condition described by Wiedemann.

The incidence of the disorder is approximately 1 in 13,700 births and is more frequently associated with in vitro fertilization (IVF). No difference in prevalence has been observed between males and females, and the condition is not race‑dependent.

Symptoms

Patients tend to exhibit excessive growth, particularly during the second half of pregnancy and in the first years of life. Adult height is usually within the normal range. Abnormal growth may also manifest as hemihyperplasia and/or macroglossia, which often leads to feeding difficulties, speech impairment, and occasionally sleep apnea. Hypoglycemia is reported in 30–50% of newborns.

Additional features include omphalocele, diastasis of the abdominal muscles, embryonal tumors, anterior ear creases, visceromegaly of abdominal organs, fetal adrenocortical cytomegaly (pathognomonic), renal abnormalities, a positive family history, and rarely cleft palate. Congenital heart defects occur in 9–34% of cases; in approximately half of these, cardiomegaly resolves spontaneously. Cardiomyopathy is rare.

Patients are highly susceptible to embryonal tumors, particularly during the first 8 years of life, with an estimated risk of approximately 7.5%.

Diagnosis

In general, the diagnosis is supported by the presence of at least three characteristic clinical features; however, embryonal tumors may also occur in individuals with milder manifestations. Positive molecular testing can confirm the diagnosis, but negative results do not exclude BWS.

Prenatal testing, including chorionic villus sampling or amniocentesis, may be offered, particularly in cases with detected cytogenetic or genomic abnormalities. Methylation defects can currently be reliably detected via amniocentesis. Amniocentesis may also be indicated when BWS‑associated findings are detected on prenatal ultrasound (e.g., fetal omphalocele). In the absence of a known molecular defect, screening may include measurement of maternal serum alpha‑fetoprotein levels and targeted fetal ultrasound examinations.

Genetic counseling is recommended. Recurrence risk assessment and cascade genetic testing should consider family history and the molecular subtype identified in the affected family member.

Treatment

Patient management typically involves standard supportive medical and surgical care. Increased surveillance for tumor development should begin when BWS is suspected or diagnosed, and also in a clinically unaffected monozygotic twin of an affected patient. Surveillance should not currently be based on genotype–phenotype correlation.

Screening for hypoglycemia should be performed in the neonatal period if prenatal findings or risk factors are present, including in clinically unaffected newborns with increased risk based on family history.

The clinical course is variable. At the severe end of the spectrum, patients are at risk of early mortality due to complications related to hypoglycemia, prematurity, cardiomyopathy, macroglossia, or tumor development. In patients who survive childhood, the overall prognosis is generally good.

• makroglosia (veľký jazyk)
• makrosómia (veľká pôrodná hmotnosť a dĺžka, ale v dospelosti normálny vzrast)
• defekty brušnej steny (omfalokéla, pupočná prietrž)
• hemihypertrofia (polovica tela je väčšia ako druhá)
• defekty ušných lalôčikov
• neonatálna hypoglykémia (nízka hladina cukru v krvi po pôrode)
• visceromegália - zväčšenie vnútrorných orgánov
• hepatomegália (zväčšenie pečene)
• nefromegália (zväčšenie obličiek)
• ďalej môže byť zväčšená slezina, pankreas, nadobličky
• polyhydramnion (zvýšené množstvo plodovej vody)
• veľká placenta
• anomália obličiek
• Wilmsov tumor (u 5-7% detí s BWS) - tumor obličky vyskytujúca sa u detí
• hepatoblastóm - zhubný nádor postihujúce pečeň u detí
• neuroblastóm - malígny nádor raného detského veku, vychádzajúci z buniek nervového tkaniva
• rhabdomyosarkóm - malígny nádor vychádzajúci z priečne pruhovaného svalu