Information about:
Beckwith-Wiedemann syndrome
What is Beckwith-Wiedemann Syndrome?
Beckwith-Wiedemann Syndrome (BWS) is a congenital overgrowth syndrome, which can affect all systems of the body. It was first recognised in 1963-64 by Dr J. Bruce Beckwith, a paediatric pathologist in America and, independently, by Dr H.E. Wiedemann, a German geneticist. Each had found a similar set of congenital abnormalities in children, which could not be found in any other disorders – in other words, a new syndrome.
BWS occurs once in approximately every 15,000 births. This figure may be an under-estimate as mild cases may not being be diagnosed. In most cases it appears to be an isolated event with no known family history, but the condition can be inherited in about 15%.
Like many such disorders, Beckwith-Wiedemann Syndrome can vary in its effects from child to child: some children are relatively mildly affected while others have a wider range of physical problems. There are, however, some characteristics that are common to most BWS children. Most problems can be helped or even solved provided that accurate diagnosis is made and appropriate treatment started. Those children who survive infancy, the great majority, are usually healthy with their growth and appearance gradually becoming normal.
What are the main characteristics of BWS? ↓
There are many characteristics that are associated with BWS, but most children who are affected have only a few of them. The most commonly found are described below:
BWS children are usually born prematurely but are larger and heavier than one would expect, given the shorter length of gestation.
MACROSOMIA (LARGE HEIGHT AND WEIGHT)
Height and weight over the 95% centile
An enlarged tongue which may cause breathing, feeding and speaking difficulties as well as excessive dribbling. It may also result in the protrusion of the lower jaw.
Reddened skin on the forehead and eyelids. This usually fades in the first few years.
These are sometimes found in conjunction with indentations behind the upper rim of the ear.
These vary in severity. The most severe is an exomphalos (omphalocele) which allows intestines and possibly other organs to protrude externally into a covering membrane. Less serious is an umbilical hernia and the least severe is diastasis recti or undue weakness and separation of the abdominal muscles.
VISCEROMEGALY
Enlarged abdominal organs, usually the kidneys, liver, spleen, adrenals and pancreas.
Low blood sugar. This occurs in approximately 40% of BWS children shortly after birth. Complications can result if it is not diagnosed and treated.
Overgrowth of one half of the body or of one limb while the rest of the body grows at a normal rate.
- WILMS TUMOUR AND HEPATOBLASTOMA
Wilms tumour occurs in the kidney and up to 5% of BWS children will develop Wilms Tumour. It is generally suggested that, in those with children with forms of BWS that put them at highr risk of BWS, an abdominal ultrasound scans should be performed every three months up to the age of 7 or 8 years. Hepatoblastoma is a rare liver tumour that may occur in children with BWS. It is less common than Wilms tumour and the risk of these diminishes after the age of 3 years. They can also be detected by abdominal ultrasound but, as not all the liver can be viewed, afp (alpha-feta-protein) levels in the blood may also be monitored 3 monthly.
CARDIOMEGALY or STRUCTURAL CARDIAC ABNORMALITIES
Enlarged heart or heart defects. These are uncommon.
Diagnosis of BWS ↓
Generally the diagnosis of BWS is made by clinical evaluation and, in most cases, is then confirmed by genetic testing. The criteria for diagnosis vary, but a firm diagnosis may be made if a child has macroglossia, anterior abdominal wall defect (e.g. exomphalos or umbilical hernia) and overgrowth. A diagnosis of BWS can also be made if only two of these major features are present but additional minor features are also present.
What is the treatment? ↓
Usually responds well to treatment with intravenous glucose and/or diet within 1 to 4 months.
If an exomphalos is present, surgery will be required soon after birth and an umbilical hernia may also sometimes need correction.
MACROGLOSSIA
Surgery may be necessary to reduce the tongue size. In some cases the tongue is accommodated successfully in the mouth as the child grows but often the lower jaw is pushed forward. Speech therapy may be necessary in some cases. Children with BWS should be considered for referral to a craniofacial team (surgeon, orthodontist and speech therapist) familiar with BWS.
TUMOUR
This will require surgery to remove the affected kidney and possibly chemotherapy and radiotherapy.
May require orthopaedic surgery.
What causes BWS? ↓
Many different types of alterations in the genetic material (DNA) may cause BWS. The different alterations (uniparental disomy, altered methylation at imprinting control centres, chromosome 11 abnormalities, gene mutations etc.) cause BWS by increasing the levels of the IGF2 growth factor and/or reducing the levels or action of the CDKN1C growth suppressor protein. The risk of one type of alteration may be increased by assisted reproductive technologies. The alteration in most cases occurs only in the affected child and in these cases there is a low risk of parents having other BWS children. In a few cases the altered gene is inherited from one parent who may or may not be mildly affected themselves. In these cases there is a 50% chance of another child being affected. The specific type of alteration detected can inform not only the familial risk bt also the risk of tumours and so families should be referred for clinical genetics assessment and testing.
