Summary of the International Consensus Recommendations for Beckwith-Wiedemann spectrum disorder (BWSp)

Diagnosis

The diagnosis of BWSp depends on the presence various of clinical features and/or genetic testing results

Each of the various clinical features are scored and a score of 2 or more is an indication for genetic testing

A diagnosis of BWSp is made if a genetic alteration is detected or, if genetic testing is negative, there is a clinical score of 4 or more

A diagnosis of BWSp might be made even if increased height and weight are absent

If genetic testing is negative then other diagnoses should be considered but if BWSp is still suspected further clinical evaluation and genetic testing can be performed

Genetic testing

Molecular genetic testing should be performed by a health professional experienced in the field of imprinting disorders.

Genetic testing should be performed in an approved laboratory with suitable expertise and recommended nomenclature should be followed in publications and test reporting

If first line genetic testing (e.g. blood methylation test) result is negative, second line molecular testing should be considered.

As the precise result of genetic testing may influence clinical management such as tumour surveillance, additional testing may be indicated if there is a positive result (e.g. mosaic paternal uniparental diploidy)

BWSp in pregnancy

Genetic testing for BWSp can be performed during pregnancy if potential features of BWSp are detected on an ultrasound scan or or if there is a relevant family history

If diagnosis of BWSp is suspected or confirmed prenatally, potential complications should be anticipated and provided for

Though there appears to be an added risk of BWSp in babies conceived with assisted reproductive technology, the risk is very small (less than 1 in 1000)

BWSp at birth

Capillary blood glucose should be monitored in newborns with a confirmed or clinical suspicion of BWSp for 48 hours

A diagnostic fasting test should be done for newborns with a suspicion of BWSp before discharge from the nursery 48 hours after birth.

If hyperinsulinism is severe and persistent, additional possible causes of hyperinsulinism should be investigated

Treatment of exomphalos should pay attention to the risk of hypoglycaemia and anaesthetic risk from macroglossia.

Macroglossia (large tongue)

Tongue reduction surgery should be considered (usually after the age of 1 year) if macroglossia causes airway obstruction or problems with feeding, marked drooling, speech, sleep, dental malocclusion or psychosocial problems (from altered appearance).

Tongue reduction surgery should be performed by an experienced surgical team following a detailed assessment by a multidisciplinary team

The results of tongue reduction surgery should be carefully audited and follow up should continue until age 16

Growth and Hemihypertrophy (lateralised overgrowth)

Postnatal growth and pubertal development should be monitored at least annually until the end of growth. There is a need for BWSp-specific growth charts

Monitoring of leg length discrepancy should be based on clinical examination and take place at least annually during childhood

Shoe lifts may be indicated for leg length discrepancy less than 2 cms. Epiphysiodesis is usually indicated for discrepancy above 2 cm. Reversible epiphysiodesis may be preferred.

Tumours surveillance

Screening for tumours should be stratified according to the genetic testing results

All children apart from those with isolated IC2 LOM should receive abdominal ultrasound screening every three months until the age of 7 to check for Wilms tumour and hepatoblastoma

Asymptomatic children with isolated IC2 LOM do not require regular ultrasound screening but there should be a low threshold for investigation if tumour related symptoms occur or there are parental concerns

Other aspects of BWSp in children

Heart: Physicians should be aware of the increased frequency of cardiac anomalies in BWSp children and a baseline cardiovascular examination performed. Individuals with clinically detected or suspected cardiovascular abnormalities should be referred for specialist cardiac assessment and echocardiography.

Cognitive development is usually normal in BWSp but should be monitored by the paediatrician.

Kidneys and urinary system: When BWSp is diagnosed, all patients should be screened for nephrourological malformations and physicians should be aware of the possibility of hypocalcuria. Physicians and radiologists should pay attention to the possibility of nephrocalcinosis and/or stones.

Transition from paediatric care to adult medicine and Adults with BWSp

Individuals with BWSp should be reviewed at the age of 16 to 18 to identify any complications needing follow up

When becoming an adult, a patient with BWSp should be given a nephrourological evaluation

Young adults with BWSp should be made aware of genetic counselling before starting a family. Genetic counselling should be performed by a health professional experienced in imprinting disorders.

General

Every patient with BWSp should have a nominated experienced health care provider who will coordinate the patient’s care.

Health professionals should be prepared to offer referrals to specialist counselling, family support services and psychological evaluation and support

Parents should be offered contact details of BWSp support groups

More research is required into long term effects of BWSp

Further details on the International Consensus Recommendations are freely available at https://www.nature.com/articles/nrendo.2017.166.pdf