Weaver syndrome is a condition that involves tall stature with or without a large head size (macrocephaly), a variable degree of intellectual disability (usually mild), and characteristic facial features. These features can include a broad forehead; widely spaced eyes (hypertelorism); large, low-set ears; a dimpled chin, and a small lower jaw (micrognathia).
People with Weaver syndrome can also have joint deformities called contractures that restrict the movement of affected joints. The contractures may particularly affect the fingers and toes, resulting in permanently bent digits (camptodactyly). Other features of this disorder can include abnormal curvature of the spine (kyphoscoliosis); muscle tone that is either reduced (hypotonia) or increased (hypertonia); loose, saggy skin; and a soft-outpouching around the belly-button (umbilical hernia). Some affected individuals have abnormalities in the folds (gyri) of the brain, which can be seen by medical imaging; the relationship between these brain abnormalities and the intellectual disability associated with Weaver syndrome is unclear.
Researchers suggest that people with Weaver syndrome may have an increased risk of developing cancer, in particular a slightly increased risk of developing a tumor called neuroblastoma in early childhood, but the small number of affected individuals makes it difficult to determine the exact risk.
The prevalence of Weaver syndrome is unknown. About 50 affected individuals have been described in the medical literature.
Weaver syndrome is usually caused by mutations in the EZH2 gene. The EZH2 gene provides instructions for making a type of enzyme called a histone methyltransferase. Histone methyltransferases modify proteins called histones, which are structural proteins that attach (bind) to DNA and give chromosomes their shape. By adding a molecule called a methyl group to histones (methylation), histone methyltransferases can turn off the activity of certain genes, which is an essential process in normal development. It is unclear how mutations in the EZH2 gene result in the abnormalities characteristic of Weaver syndrome.
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. In a small number of cases, an affected person inherits the mutation from one affected parent.
Other Names for This Condition
- Camptodactyly-overgrowth-unusual facies
- Weaver-Smith syndrome
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
- Al-Salem A, Alshammari MJ, Hassan H, Alazami AM, Alkuraya FS. Weaver syndrome and defective cortical development: a rare association. Am J Med Genet A. 2013 Jan;161A(1):225-7. doi: 10.1002/ajmg.a.35660. Epub 2012 Dec 13. Citation on PubMed
- Coulter D, Powell CM, Gold S. Weaver syndrome and neuroblastoma. J Pediatr Hematol Oncol. 2008 Oct;30(10):758-60. doi: 10.1097/MPH.0b013e3181758974. Citation on PubMed
- Crea F. Histone code, human growth and cancer. Oncotarget. 2012 Jan;3(1):1-2. Citation on PubMed or Free article on PubMed Central
- Cross NC. Histone modification defects in developmental disorders and cancer. Oncotarget. 2012 Jan;3(1):3-4. Citation on PubMed or Free article on PubMed Central
- Gibson WT, Hood RL, Zhan SH, Bulman DE, Fejes AP, Moore R, Mungall AJ, Eydoux P, Babul-Hirji R, An J, Marra MA; FORGE Canada Consortium, Chitayat D, Boycott KM, Weaver DD, Jones SJ. Mutations in EZH2 cause Weaver syndrome. Am J Hum Genet. 2012 Jan 13;90(1):110-8. doi: 10.1016/j.ajhg.2011.11.018. Epub 2011 Dec 15. Citation on PubMed or Free article on PubMed Central
- Neylon OM, Werther GA, Sabin MA. Overgrowth syndromes. Curr Opin Pediatr. 2012 Aug;24(4):505-11. doi: 10.1097/MOP.0b013e3283558995. Review. Citation on PubMed
- Tatton-Brown K, Hanks S, Ruark E, Zachariou A, Duarte Sdel V, Ramsay E, Snape K, Murray A, Perdeaux ER, Seal S, Loveday C, Banka S, Clericuzio C, Flinter F, Magee A, McConnell V, Patton M, Raith W, Rankin J, Splitt M, Strenger V, Taylor C, Wheeler P, Temple KI, Cole T; Childhood Overgrowth Collaboration, Douglas J, Rahman N. Germline mutations in the oncogene EZH2 cause Weaver syndrome and increased human height. Oncotarget. 2011 Dec;2(12):1127-33. Erratum in: Oncotarget. 2018 Nov 30;9(94):36719. Citation on PubMed or Free article on PubMed Central
- Tatton-Brown K, Murray A, Hanks S, Douglas J, Armstrong R, Banka S, Bird LM, Clericuzio CL, Cormier-Daire V, Cushing T, Flinter F, Jacquemont ML, Joss S, Kinning E, Lynch SA, Magee A, McConnell V, Medeira A, Ozono K, Patton M, Rankin J, Shears D, Simon M, Splitt M, Strenger V, Stuurman K, Taylor C, Titheradge H, Van Maldergem L, Temple IK, Cole T, Seal S; Childhood Overgrowth Consortium, Rahman N. Weaver syndrome and EZH2 mutations: Clarifying the clinical phenotype. Am J Med Genet A. 2013 Dec;161A(12):2972-80. doi: 10.1002/ajmg.a.36229. Epub 2013 Nov 8. Citation on PubMed
- Tatton-Brown K, Rahman N. The NSD1 and EZH2 overgrowth genes, similarities and differences. Am J Med Genet C Semin Med Genet. 2013 May;163C(2):86-91. doi: 10.1002/ajmg.c.31359. Epub 2013 Apr 16. Citation on PubMed or Free article on PubMed Central