Why Test Tissue for BWS After a Normal Blood Test?

When a child has signs of Beckwith-Wiedemann syndrome (BWS) but their blood test comes back normal, a geneticist may ask to test another type of tissue, such as skin, cheek cells, or tissue removed during a surgery. This happens because of a phenomenon called epigenetic mosaicism, where the genetic changes that cause BWS are only present in some of the body’s cells and might be completely missing from the blood ^[1]. Testing the exact tissues that are overgrown or affected by BWS gives doctors a much better chance of finding the hidden genetic change, which is crucial for guiding your child’s medical care and tumor screenings ^[2][3].

Understanding Epigenetic Mosaicism

To understand why this happens, it helps to know how BWS develops. BWS is an “imprinting disorder,” meaning it involves changes in how certain genes (specifically a cluster on chromosome 11) are turned on or off ^[4]. In many children with BWS, these changes happen shortly after conception as the embryo is growing.

Because the change occurs after the first few cells have already formed, not every cell in the baby’s body will carry the BWS gene changes. This mixture of affected and unaffected cells in one person is called somatic mosaicism or epigenetic mosaicism ^[5].

Think of it like a marble cake: if you take a crumb from one part of the cake, you might get chocolate (affected cells), but if you take a crumb from another part, you might only get vanilla (unaffected cells). If the blood cells develop from the “vanilla” part of the embryo, a standard blood test will come back perfectly normal, even though the child clearly has BWS in other parts of their body ^[6].

Secondary Tissues Used for Testing

Because BWS changes might be limited to specific organs or tissues (known as organ-specific mosaicism) ^[3], testing a different sample can uncover the diagnosis that the blood test missed. Testing multiple tissues prevents false-negative results ^[5]. Doctors will usually choose the testing method based on what is least invasive and most practical for your child at the time. Common secondary tissues used for testing include:

• Buccal (Cheek) Swabs: Often the first secondary step because it is non-invasive. It is a simple, painless swab of the inside of the cheek to collect cells.
• Surgical Waste Tissue: If your child is already scheduled for a necessary surgery—such as a tongue reduction for an enlarged tongue (macroglossia) or a repair for an abdominal wall defect (omphalocele)—the surgical team can safely save a small piece of the removed tissue for genetic testing. This is highly effective because doctors are directly testing the tissue visibly affected by the syndrome ^[3]. Important: Collecting this sample does not change the safety, length, or outcome of your child’s surgery in any way.
• Skin Fibroblasts: Cells taken from a small skin biopsy, often from an area of the body showing overgrowth (hemihypertrophy). Unlike a cheek swab, a biopsy is a minor invasive procedure that involves taking a tiny sample of skin. It is usually performed with local numbing medicine to minimize discomfort. Doctors may opt for this if a cheek swab is negative and no surgeries are planned.

A Critical Note on Surgical Tissue: If your child is having surgery, you must explicitly confirm with both your geneticist and the surgeon beforehand that they have communicated about saving the tissue. The lab needs to be prepared to receive the sample so that it is not accidentally thrown away.

Keep in mind that testing these tissues, especially skin or surgical samples, can sometimes take several weeks to yield results because the cells may need to be grown (cultured) in the laboratory.

Why Confirming the Exact Change Matters

You might wonder if you even need this secondary test if your child’s doctor already suspects BWS based on physical symptoms. Finding the specific genetic or epigenetic change (the “molecular subtype”) is incredibly important for your child’s future ^[2].

BWS is not exactly the same in every child. There are several different molecular causes, and each carries its own specific health risks. Most importantly, your child’s tumor risk—the likelihood of developing childhood cancers like Wilms tumor or hepatoblastoma—depends heavily on which specific molecular change they have ^[1][7]. Identifying the exact cause through tissue testing allows doctors to create a customized, evidence-based tumor surveillance plan ^[8]. This ensures your child gets the right ultrasounds and bloodwork at the right times to keep them safe and healthy ^[9].