Diagnosis

I've been reading a bit, but I've been so, so busy and haven't yet been able to comment.. I haven't forgotten all of you! And I will be blogging away about lots of stuff pretty soon. But, for now, I just wanted to post this- now that Aeson has indeed been diagnosed with it. He has the difference in the chromosome and will now undergo blood/urine tests and sonograms regularly for all of his childhood.. starting this Friday. I can't write all my thoughts/feelings right now.. but just, as you read this, imagine it was your child.

What is Beckwith-Wiedemann syndrome?

Beckwith-Wiedemann syndrome (BWS) is a growth regulation disorder. The most common features of BWS include macrosomia (large body size), macroglossia (large tongue), abdominal wall defects, an increased risk for childhood tumors, kidney abnormalities, hypoglycemia (low blood sugar) in the newborn period, and unusual ear creases or pits. Children with BWS may also have hemihyperplasia, in which some parts of the body are larger on one side than on the other.

The major features of BWS, macrosomia and macroglossia, are often present at birth. Abdominal wall defects such as omphalocele, which causes the inside of the abdomen to protrude through the navel, are also present at birth and may require surgery before an infant leaves the hospital. Mothers of children with BWS may have pregnancy complications, including premature delivery and polyhydramnios (excess amniotic fluid). An unusually large placenta and long umbilical cord may also be present.

The increased growth rate generally slows during childhood. Intellectual development is usually normal, and adults with BWS typically do not experience any medical problems related to their condition.

What causes BWS?

BWS is a genetic condition related to changes in the genes (in an area called the short arm) of chromosome 11 (11p15.5). In most cases (about 85%), the genetic changes that cause BWS happen sporadically (occurs by chance) in families where there is no history of the condition. In about 10% to 15 % of cases, the genetic changes may be inherited. This means that the risk for BWS can be passed from generation to generation in a family. The genetic mechanisms that cause gene mutations (alterations) resulting in BWS are complex.

How is BWS inherited?

The 10% to 15% of BWS that is inherited follows an autosomal dominant inheritance pattern. Normally, every cell has two copies of each gene: one inherited from the mother and one inherited from the father. In autosomal dominant inheritance, a mutation happens in only one copy of the gene. This means that a parent with a gene mutation may pass along a copy of their normal gene or a copy of the gene with the mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has a 50% chance of having the same mutation.

How common is BWS?

BWS has been found across different population groups. Approximately one in 13,700 people have BWS. Some researchers believe this number could be an underestimate.

How is BWS diagnosed?

The diagnosis of BWS is clinical, meaning that it is based primarily on physical features. BWS is suspected in children who are larger than expected for their age, especially if growth is not symmetrical (the same on both sides). An enlarged tongue and abdominal wall defect, primarily omphalocele, are also considered to be common features. There are many other features that may be seen in some children with BWS. However, not every child with BWS will have every feature. Features are listed as major (common) or minor (less common). It is generally agreed that at least one major feature and two minor features are required to consider a diagnosis of BWS:

Major Features

* Macrosomia (large body size)

* Macroglossia (large tongue)

* Omphalocele (abdomen protrudes through navel)

* Hemihyperplasia (some parts of the body are larger on one side)

* Ear creases or pits

* Visceromegaly (enlargement of one or more abdominal organ)

* Embryonal tumor (Wilms tumor, hepatoblastoma, neuroblastoma, rhabdomyosarcoma)

* Adrenocortical tumor

* Kidney abnormalities

* Cleft palate (gap in the roof of the mouth)

* Family history of BWS

Minor Features

* Polyhydramnios (excessive amniotic fluid)

* Prematurity (low birth weight)

* Hypoglycemia (low blood sugar)

* Advanced bone age

* Heart problems

* Diastatsis recti (separation of the right and left sides of the main abdominal muscle)

* Hemangioma (noncancerous tumor made up of blood vessels)

* Facial nevus flammeus (hemangioma of the skin, also called a “port-wine stain”)

* Characteristic facial features

* Identical twins

Genetic testing for gene mutations associated with BWS is available, but is complex. It is recommended that families considering genetic testing for BWS meet with a clinical geneticist and genetic counselor that can explain the tests and coordinate testing. Currently available genetic testing methods may be able to identify up to 80% of genetic mutations causing BWS.

What are the estimated cancer risks associated with BWS?

The estimated risk for tumors in children with BWS is about 7.5%. Tumors are very rare after age 10, and the risk for an individual tumor decreases over time until the risk is similar to that of the general population. Several different tumor types, both cancerous and benign (noncancerous), have been reported in children with BWS. The most common tumor types are:

* Wilms tumor (kidney tumor)

* Hepatoblastoma (liver tumor)

* Adrenocortical carcinoma

* Neuroblastoma

* Rhabdomyosarcoma

What are the screening options for BWS?

Current suggested screenings for people who are known or suspected to have BWS include:

* Baseline magnetic resonance imaging (MRI) or computed tomography (CT or CAT) scan of the abdomen, at the time of diagnosis

* Abdominal ultrasound to view kidneys, liver and adrenal gland every three months, until age 8

* Serum alpha-fetoprotein every three months, until age 4

* Regular physical examination, including abdominal exam; schedule determined by your doctor


Most children (>80%) with BWS do not develop cancer; however, children with BWS are much more likely (~600 times more) than other children to develop certain childhood cancers, particularly Wilms' tumor (nephroblastoma) and hepatoblastoma.[1] Individuals with BWS appear to only be at increased risk for cancer during childhood (especially before age four) and do not have an increased risk of developing cancer in adulthood.[1] If 100 children with BWS were followed from birth until age ten, about 10 cases of cancer would be expected in the group before age four, and about 1 case of cancer in the group would be expected between age four and ten.

In addition to Wilms tumor and hepatoblastoma, children with BWS are also at increased risk of developing adrenal cortical carcinoma, neuroblastoma, and rhabdomyosarcoma.

Both Wilms tumor and hepatoblastoma can usually be cured if diagnosed early. Early diagnosis allows physicians to treat the cancer when it is low stage. In addition, there is less toxic treatment.[9] Given the importance of early diagnosis, all children with BWS should receive cancer screening.

In general, the prognosis is very good. Children with BWS usually do very well and grow up to become the heights expected based on their parents heights. While children with BWS are at increased risk of childhood cancer, most children with BWS do not develop cancer and the vast majority of children who do develop cancer can be treated successfully.

Children with BWS for the most part had no significant delays when compared to their siblings. However, some children with BWS do have speech problems that could be related to macroglossia or hearing loss.

Advances in treating neonatal complications and premature infants in the last twenty years have significantly improved the true infant mortality rate associated with BWS. In a review of pregnancies that resulted in 304 children with BWS, not a single neonatal death was reported.[11] This is compared to a previously reported mortality rate of 20%.[12] The data from the former study was derived from a BWS registry, a database that may be slightly biased towards involving living children; however, death was not an exclusion criterion to join the registry. This suggests that while infants with BWS are likely to have a higher than normal infant mortality risk, it may not be as high as 20%.