Beckwith-Wiedemann syndrome (BWS) is a genetic overgrowth condition that affects roughly 1 in every 11,000 births. Babies born with BWS tend to be larger than average, with distinctive features that can include an enlarged tongue, abdominal wall defects, and low blood sugar in the newborn period. The good news: most children and adults with BWS live normal, healthy lives, and the accelerated growth typically slows down by around age 8.
How BWS Affects the Body
The hallmark features of BWS are present at birth or become apparent in early infancy. Not every child has all of them, and severity varies widely.
An enlarged tongue (macroglossia) is one of the most recognizable signs. In mild cases, the tongue may stick out slightly but cause no functional problems. In more significant cases, it can interfere with feeding, speech development, and dental alignment, and may contribute to drooling. About 70% of children who need surgical tongue reduction have a combination of these issues rather than just one. When surgery is performed, outcomes for speech, feeding, and oral function are generally positive, with preservation of both motor and sensory function.
Abdominal wall defects are another common feature. These range from a small umbilical hernia to an omphalocele, a more serious condition where abdominal organs protrude through the belly button into a thin membrane. An omphalocele typically requires surgical repair shortly after birth.
Many children with BWS also experience asymmetric growth, where one side of the body grows noticeably larger than the other. This is called hemihyperplasia, and it can affect a single limb, one side of the face, or even internal organs. The asymmetry usually becomes less noticeable over time.
Low Blood Sugar in Newborns
About half of babies with BWS develop low blood sugar (hypoglycemia) shortly after birth. This happens because the pancreas produces too much insulin, which pulls sugar out of the bloodstream faster than normal. For most infants, this resolves on its own within the first days or weeks of life. In a small number of cases, the low blood sugar persists and requires more intensive treatment, occasionally including partial removal of the pancreas. Early detection and monitoring in the newborn period is important because prolonged low blood sugar can affect brain development.
What Causes BWS
BWS isn’t caused by a single broken gene in the traditional sense. Instead, it results from disruptions to a process called genomic imprinting on chromosome 11. Normally, certain genes are active only from the copy you inherited from your mother, while others are active only from your father’s copy. This selective silencing is controlled by chemical tags (methyl groups) attached to DNA.
In BWS, these tags end up in the wrong place, causing genes that promote growth to become overactive or genes that restrain growth to be silenced. The most common pattern, accounting for about 50% of cases, involves loss of a methyl tag on the maternal copy of a region called IC2. This leads to reduced activity of a growth-suppressing gene called CDKN1C. Another pattern involves gaining an extra methyl tag at a different region (IC1), which causes overproduction of a powerful growth factor called IGF2. A third mechanism is paternal uniparental disomy, where a child inherits two copies of this chromosome region from their father and none from their mother. Together, DNA methylation defects at these two regions account for roughly 60% of all BWS cases.
Most cases of BWS occur sporadically, meaning neither parent has the condition. In a smaller percentage of families, a specific gene variant can be inherited from the mother.
How BWS Is Diagnosed
Diagnosis relies on a combination of clinical features and molecular testing. An international consensus established a scoring system in which certain features (like an omphalocele, macroglossia, or hemihyperplasia) earn points. A score of 4 or higher supports a clinical diagnosis of classic BWS even without molecular confirmation, though genetic testing of the 11p15 region is recommended to identify the specific subtype. The subtype matters because it directly influences cancer risk and the intensity of monitoring a child will need.
Childhood Cancer Risk
Children with BWS face an elevated risk of certain embryonal tumors, particularly Wilms tumor (a kidney cancer) and hepatoblastoma (a liver cancer). Overall, tumors develop in about 10% of children with BWS. A large German study of 321 children with molecularly confirmed BWS found a 33-fold increased cancer risk compared to the general childhood population, with hepatoblastoma and Wilms tumor being the most frequent. Neuroblastoma and adrenal tumors can also occur, though less commonly.
The level of risk depends heavily on the molecular subtype. Children with loss of methylation at IC2, the most common subtype, have a cumulative childhood cancer risk below 3%. Children with other subtypes, particularly those with paternal uniparental disomy or gain of methylation at IC1, face higher risk and require closer surveillance.
Screening and Monitoring
Because most BWS-associated tumors appear in early childhood, screening protocols are concentrated in the first several years of life. Current expert recommendations call for abdominal ultrasound every three months starting at birth (or whenever the diagnosis is made), continuing until the child’s seventh birthday for Wilms tumor surveillance. For hepatoblastoma, screening includes both abdominal ultrasound and a blood test measuring alpha-fetoprotein (AFP, a protein that rises when liver tumors are present) every three months until the third birthday.
These frequent scans may sound intense, but they serve a clear purpose: tumors caught early through screening tend to be at an earlier stage and are more treatable. If AFP levels spike significantly, doctors typically repeat the measurement after about six weeks and re-examine imaging before taking further steps.
Growth and Long-Term Outlook
Children with BWS grow faster than their peers in early childhood, but this accelerated pace slows around age 8. Adults with BWS are not unusually tall. The asymmetric growth from hemihyperplasia also tends to become less pronounced with age, though some difference between sides may remain.
Life expectancy for people with BWS is normal. Most adults with the condition do not have serious ongoing medical problems related to it. The main period of active medical concern is childhood, when cancer screening, management of low blood sugar, and any needed surgical interventions (for tongue size or abdominal wall repair) take place. Once a child ages out of the high-risk window for tumors, the condition largely becomes part of their medical history rather than an ongoing clinical challenge.