Weaver syndrome




Weaver syndrome is a rare congenital disorder associated with rapid growth beginning in the prenatal period and continuing through the toddler and youth years. It is characterized by advanced osseous maturation, and distinctive craniofacial, skeletal, and neurological abnormalities. It was first described by Dr. David Weaver in 1974.


Children with Weaver syndrome tend to look similar and have distinctive physical and craniofacial characteristics, which may include several, but not all of the following features:

  • Macrocephaly
  • Large bifrontal diameter
  • Flattened occiput
  • Long philtrum
  • Retrognathia
  • Round face in infancy
  • Prominent chin crease
  • Large ears
  • Strabismus
  • Hypertelorism
  • Epicanthal folds
  • Downslanting palpebral fissures

Other features may include loose skin, thin deep-set nails, thin hair, short ribs, limited elbow and knee extension, camptodactyly, and a coarse, low-pitched voice. Delayed development of motor skills such as sitting, standing, and walking are commonly exhibited in early childhood. Patients with Weaver syndrome typically have mild intellectual disability with poor coordination and balance. They also have some neurological abnormalities such as speech delay, seizures, mental retardation, hypotonia or hypertonia, and behavioral problems.


A common cause for Weaver syndrome is mutations in the EZH2 gene on chromosome 7q36. EZH2 (Enhancer of Zeste, Drosophila, homolog 2), is the second histone methyltransferase associated with human overgrowth. It encodes the catalytic component of the PRC2 protein complex (Polycomb Repressive Complex 2), which regulates chromatin structure and gene expression, and has been found to repress transcription. EZH2 also has critical roles in stem cell maintenance and cell lineage determination, such as osteogenesis, myogenesis, lymphopoiesis and hematopoiesis.

It can also be associated with mutations in the histone methyltransferase NSD1 gene on chromosome 5q35. The functions of NSD1 are not clearly known, but it is thought to act as a factor in influencing transcription, which contains domains involved in chromatin-mediated regulation during development.

Most cases are found to be sporadic, with no family history of the syndrome, although there have been a few cases in families where autosomal dominant inheritance has been reported.


The phrase "signs of Weaver Syndrome" should, strictly speaking, refer only to those signs and symptoms of Weaver Syndrome that are not readily apparent to the patient. The word "symptoms of Weaver Syndrome" is the more general meaning; see symptoms of Weaver Syndrome. The signs and symptom information on this page attempts to provide a list of some possible signs and symptoms of Weaver Syndrome. This medical information about signs and symptoms for Weaver Syndrome has been gathered from various sources, may not be fully accurate, and may not be the full list of Weaver Syndrome signs or Weaver Syndrome symptoms. Furthermore, signs and symptoms of Weaver Syndrome may vary on an individual basis for each patient. Only your doctor can provide adequate diagnosis of any signs or symptoms and whether they are indeed Weaver Syndrome symptoms.


With appropriate treatment and management, patients with Weaver syndrome appear to do well, both physically and intellectually, throughout their life and have a normal lifespan. Their adult height is normal as well.


There is no cure available for Weaver syndrome. However, with multidisciplinary management such as neurological, pediatric, orthopedic, and psychomotor care and genetic counseling, symptoms can be managed. Surgery may be used to correct any skeletal issues. Physical and occupational therapy are considered an option to help with muscle tone. Also, speech therapy is often recommended for speech related problems.