What is Weaver syndrome?

Weaver syndrome is a disease caused by mutations – or genetic changes – in the EZH2 gene. It is characterized by macrosomia, a distinctive shape of the face, and variable intellectual impairment.

How is Weaver syndrome diagnosed?

Suspected Diagnosis

Weaver syndrome is suspected with presentation of the following:

Clinical:

  • Macrosomia (≥ 97th percentile)

  • Large head circumference (≥ 97th percentile)

  • Intellectual impairment

  • Distinctive shape of the face

    • Rearward displacement of the jaw (especially in children < 3 years of age)
    • Large, low-lying ears (especially in children < 3 years of age)
    • Horizontal chin fold, sometimes with a central dimple (especially in children < 3 years of age)
    • Round face (especially in children)
    • Broad forehead
    • Wide distance between the eyes
    • Almond-shaped eyes

  • Lack of coordination

  • Soft and doughy skin

  • Immovable, curved fingers and/or toes

  • Umbilical hernia

  • Changes in muscle tension (reduced muscle tension in the torso and/or increased muscle tension in the arms and legs)

  • Rough and deep crying in infants

Radiological:

  • Advanced bone age

  • Changes in the MRI of the head

Genetic Diagnostics

The diagnosis of “Weaver syndrome” is confirmed by detection of a mutation – or genetic change – in the EZH2 gene.

What is the risk of cancer?

To date, tumors associated with Weaver syndrome have only been described in individual cases: one patient with lymphoma, one patient with neuroblastoma (a tumor of the nerve cells of the involuntary nervous system) and acute lymphatic leukemia (ALL), and one other patient with neuroblastoma. There may be an increased risk of developing neuroblastomas.

In addition, the following manifestations may occur as part of Weaver syndrome:

  • Macrosomia (≥ 97th percentile): in nearly all patients

  • Large head circumference (≥ 97th percentile): in around 50% of patients

  • Intellectual impairment: There is usually mild to moderate developmental delays, which may present themselves in speech and as a learning disability. There is considerable overall variability, ranging from normal intellectual development to severe mental retardation.

  • Distinctive shape of the face (see suspected diagnosis)

  • Manifestations of the bones: advanced bone age, curvature of the spine, immovable, curved fingers and/or toes, boutonniere (buttonhole) deformity of the fingers, clubfoot

  • Connective tissue manifestations: soft and doughy skin, hypermobile joints, flat feet, umbilical hernia

  • Change in muscle tension: reduction in central muscle tension and/or increase in peripheral muscle tension

  • Feeding problems in newborns

  • Rough and deep crying in infants

  • Anomalies in the MRI of the head

What causes Weaver syndrome?

Weaver syndrome is caused by mutations – or genetic changes – in the EZH2 gene. This gene encodes for the EZH2 protein, which is necessary for reading and amplifying DNA – or genetic material – in our body,

Now if the EZH2 gene is altered, the EZH2 protein will not be produced properly and will no longer be able to perform its normal function. This can result in the defective development of various structures in our body.

Weaver syndrome can be passed on by parents to their children. In these cases, it is inherited as an autosomal dominant disease. However, it is also possible for a spontaneous or new mutation – called a de novo mutation – to occur.

Is there a treatment?

In light of the large number of potential manifestations, treatment should always be symptom-orientated and involve different specialist disciplines working together.

Patients with developmental delays and/or a learning disability can receive learning, behavioral, and/or speech therapy.

Long-term physical therapy can also help to delay operations and reduce pain.

Surveillance Recommendations for the Early Detection of Cancer

Surveillance Recommendations

There are no standard surveillance recommendations to date. Patients with Weaver syndrome should undergo regular examinations (e.g. once a year), particularly with regard to cognitive and speech development, changes in the fingers or feet, and reduced muscle tension. If no complications are clinically evident, the examination interval can be lengthened starting in adolescence.

If there is curvature of the spine (scoliosis), care should be provided in line with orthopedic recommendations.

If any other anomalies are found, other examinations should be conducted as needed and the patient referred to specialists.

Patients should be informed about their potentially increased risk of neuroblastoma. Specific cancer surveillance is not recommended.

Self-Care and Support

What should I pay special attention to?

You should see a doctor as soon as changes in the spine or joints occur. In addition, restricted movement in the fingers or toes and weakening muscles should be noted and reported to a doctor as well. You should likewise go to a doctor if new anomalies or complaints develop.

Support Groups and Additional Information

Unfortunately, we are as yet unaware of any existing support groups for patients with Weaver syndrome. We will add new information as it becomes available.