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 because of mild cases not being diagnosed. Cases have been reported in most developed countries. In the great majority of cases it appears to be an isolated event with no known relatives, but there is some evidence that the condition can be inherited.

Like many such disorders, Beckwith-Wiedemann Syndrome can vary in its effects from child to child i.e. 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:

PREMATURITY

BWS children are usually born prematurely but are larger and heavier than one would expect, given the shorter length of gestation.

MACROSOMIA

Height and weight over the 95% centile

MACROGLOSSIA

An enlarged tongue, which may cause breathing, feeding and speaking difficulties, as well as excessive dribbling. It may increase susceptibility to respiratory problems such as bronchitis or excess mucus. It may also result in the protrusion of the lower jaw.

NEVUS FLAMMEUS

Reddened skin on the forehead and eyelids. This usually fades in the first few years.

EAR LOBE CREASES

These are sometimes found in conjunction with indentations behind the upper rim of the ear.

WILMS TUMOURS

Tumours of the kidney. Around 7.5% of BWS children will develop Wilms Tumour. Because of the aggressiveness of these tumours, abdominal ultrasound scans should take place every three months up to the age of 7 or 8 years.  A baseline MRI scan may also be performed. The susceptibility to these tumours diminishes and is not usually a problem after the age of 8.

Please note that not all children with BWS are at risk of Wilms tumour and therefore do not require ultrasound scans. See the GOSH information sheet referred to below.

ABDOMINAL WALL DEFECTS

These vary in severity. The worst problem is an omphalocele which allows intestines and possibly other organs to protrude externally into a covering membrane. Less serious is an umbilical hernia and the least worse case is undue weakness and separation of the abdominal muscles, which leads to a pot-bellied appearance. Lax abdominal musculature can cause problems with constipation.

VISCEROMEGALY

Enlarged abdominal organs, usually the kidneys, liver, spleen, adrenals and pancreas.

HYPOGLYCAEMIA

Low blood sugar. This occurs in approximately 40% of BWS children shortly after birth. Brain damage and other complications can result if it is not diagnosed and treated.

HEMIHYPERTROPHY

Overgrowth of one half of the body or of one limb while the rest of the body grows at a normal rate.

HEPATOBLASTOMA

Liver tumours. 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. As the risk of these tumours is so low, this test is not usually carried out in the UK.

CARDIOMEGALY or STRUCTURAL CARDIAC ABNORMALITIES

Enlarged heart or heart defects. These are relatively uncommon and may resolve without treatment.

Psychomotor development is usually normal except in cases of undiagnosed hypoglycaemia or other complications.

Diagnosis of BWS

Generally the diagnosis of BWS is made by a combination of clinical evaluation and  molecular 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. Polyhydramnoios (excessive water) during pregnancy is also associated with BWS. Genetic testing involves taking a blood sample so it is important that your son or daughter is seen by a Clinical Geneticist. Please note that in around 20% of BWS children there is no detectable molecular cause i.e. the blood test will not confirm BWS.

What is the treatment?

HYPOGLYCAMIA

Usually responds well to treatment with hydrocortisone, intravenous glucose and/or diet within 1 to 4 months.

ABDOMINAL WALL DEFECTS

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 can be pushed forward. Some operations for tongue reduction are done before the child is a year old. Speech therapy may be necessary in some cases. BWS children should be considered for review by a craniofacial team (surgeon, orthodontist and speech therapist) familiar with BWS. The national service for macroglossia for BWS children in the UK is Great Ormond Street Hospital. Please see: www.gosh.nhs/health-professionals/clinical-specialities/speech-and-language-therapy-information-for-health-professionals/services-we-provide/multidisciplinary-macroglossia-service-for-children-with-BWS

WILMS TUMOUR

This will require surgery to remove the affected kidney and possibly chemotherapy and radiotherapy.

HEMIHYPERTROPHY

May require orthopaedic surgery though is often treated with a shoe lift.

What causes BWS?

Recent research has shown that BWS is caused by an alteration in genetic material in particular at chromosome 11p15. The alteration in most cases occurs only in the affected child. 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. For a more detailed explanation of the causes of BWS please see the very useful information sheet on the Great Ormond website. This can be found at http://www.gosh.nhs.uk/medical-information/search-medical-conditions/beckwith-wiedemann-syndrome