Beckwith-Wiedemann syndrome (BWS) (2024)

The most common features of the conditioninclude:

• Increased height and weight at birthor in childhood.
• Asymmetry of growth, for exampleone arm or leg larger than the other(hemihypertrophy).
• Large tongue size (macroglossia).
• Low blood sugar in the first few days orweeks of life (neonatal hypoglycaemia).
• Umbilical hernia or other abdominal walldefect, for example exomphalos where theintestines and sometimes other organs suchas the liver remain inside the umbilical cordbut outside the abdomen at birth.
• Some children with the condition are atrisk of Wilms' tumour of the kidney.

Other features of the condition includesubtle alterations in the shape of the earsand, rarely, cleft palate or a congenital heartdefect. Tumours other than Wilms' tumour,for example hepatoblastoma (childhood livertumour), occasionally occur in childhood butare much less common.Learning difficulties are not part of thecondition other than in the very smallnumber of children with a complexchromosome abnormality.

BWS is caused byabnormalities at chromosome 11p15. There area number of different abnormalities that wesee. The names are quite complicated, but areimportant to the doctors so they can give youthe right advice.Most of these cannot be inherited and havea very low chance of happening again in thefamily. These include:

• KvDMR hypomethylation (this is the causeof 50 per cent of children with BWS).
• Paternal uniparental disomy 11p15, oftenwritten UPD 11p15 (20 per cent).
• H19 hypermethylation (five per cent).

A few can be inherited and can have anincreased chance of happening again in thefamily. These include:Approximately 20 per cent of children withBWS have nodetectable molecular cause using currenttechniques. The cause in these children is notknown.Your clinical geneticist will be able to explainthe genetic test results to you and into whichgroup your child falls.

• CDKN1C mutations (five per cent).
• Paternal 11p15 duplication, often as part ofa chromosome translocation (one per cent).
• H19 microdeletion (less than one per cent).

The treatments and medical follow-uprequired depend on the clinical features of thechild and the molecular results. All childrenshould be seen by a clinical geneticist atinitial diagnosis to advise on follow-up andthe chance or recurrence of the conditionin the family. Where there is a high risk ofrecurrence, the family will have the chance toask about testing in pregnancy.Children will often have regularappointments with a general paediatricianduring early childhood.

When they are first born, all children shouldhave monitoring of their blood sugars beforefeeds for 48 hours. This may need to continue,for example if measurements are low.Children born with a major abdominal walldefect (exomphalos) will usually requiresurgery in the first few days of life. This willusually have been detected during pregnancyand the family aware of the need for surgery.Children with hemihypertrophy affecting thelegs should be referred for assessment by anorthopaedic surgeon. In many cases, all that isrequired is a shoe orthotic such as a heel raise.Some children undergo minor surgery later inchildhood to slow the growth of the longer leg.

Macroglossia may cause difficulties withfeeding, speech, the development of theteeth and jaws, and increased drooling. Aspecialist speech and language therapist canprovide support from infancy. Referral to aspecialist team is often beneficial. There is anational specialised service for children whohave macroglossia associated with BWSat GOSH. The aim of the service is to preventor resolve the problems associated withmacroglossia and to enable the best functionaloutcome. Some children may require tonguereduction surgery.

Some children with BWS are at increased risk of Wilms' tumour of the kidney. Wilms' tumour usuallyoccurs in young children under the age of fiveyears. It is very well treated and is cured inaround 90 per cent of children.Wilms' tumour has never been reported inchildren with BWS caused by KvDMR hypomethylation. This is thecommonest cause of BWS. Thousands of children with KvDMRhypomethylation have now been followed upand it is clear that they do not need Wilms' tumour surveillance.

For all other children with BWS, we recommend kidneyultrasound scans every three to four monthsuntil the age of seven years.Tumours other than Wilms' tumour areuncommon in BWS. As they are uncommon andbecause there are no reliable screening tools,we do not recommend specific surveillanceother than for Wilms' tumour.