127 - beckwith-wiedemann syndrome

(EMG-exomphalos+macroglossia+gigantism)

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. Children with one side of the body bigger than the other or enlarged kidneys appear to be more susceptible to Wilms tumour than other BWS children.

Dr. Beckwith recommends that if a brother or sister has one or two of the characteristics of BWS then that child should also have ultrasound scans every three months.

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 are also monitored 3 monthly.

CARDIOMEGALY or STRUCTURAL CARDIAC ABNORMALITIES

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

Diagnosis of BWS

Currently diagnosis of BWS is made by clinical evaluation and not by genetic testing. Diagnosis is generally based upon the child showing two out of the five major characteristics. These major characteristics are: macroglossia; unexplained hypoglycaemia in the first four months; ear creases or pits; abdominal wall defect (even a mild umbilical hernia); and macrosomia at birth.

What is the treatment?

HYPOGLYCEMIA

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

ABDOMINAL WALL DEFECTS

If an omphalocele is present, surgery will be required soon after birth and an umbilical hernia may also sometimes need correction. Constipation may require medication.

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. Some operations for tongue reduction are done before the child is a year old. Speech therapy may be necessary in some cases. All BWS children should be reviewed by a craniofacial team (surgeon, orthodontist and speech therapist) familiar with BWS.

WILMS TUMOUR

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

HEMIHYPERTROPHY

May require orthopaedic surgery.