About Weaver Syndrome And What Is Known About Its Genetics

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What Is Weaver Syndrome?

Weaver Syndrome (WS) is a medical condition that causes many growth and developmental defects individuals who are inflicted with it. Specifically, a person who has WS is likely to display a few or more of the following defects and symptoms:

  • Accelerated physical growth of the body (which usually begins at or even before birth)
  • Mental retardation
  • Seizure
  • Behavioral problems
  • Thin hair (on head)
  • Large forehead
  • Widely-spaced eyes
  • Smallish jaw
  • Cleft lip
  • Overgrown ears
  • Large hands and fingers
  • Fingers that are cannot be straightened
  • Thin finger nails
  • Various foot abnormalities, such as abnormally shaped feet and feet having high-arches, for example
  • Increased muscle tone
  • Sagging, droopy skin
  • Abnormally developed genitalia
  • Hoarse voice and slurred speech
  • Difficulty swallowing
  • Difficulty breathing

There is no cure for WS and treating it can be challenging. Usually WS symptoms are treated by a multi-disciplanary team of medical professionals, which often includes a pediatrician, orthopedist, plastic reconstructive surgeon, physical therapist and speech therapist, among others. Absent any overly severe symptoms, WS sufferers usually live a normal lifespan.

There have only been roughly 30 cases of WS ever reported, meaning that WS is one of the rarest genetic disorders ever seen. Despite the limited number of known WS cases, human molecular geneticists have studied this condition to such an extent that they have uncovered an underlying genetic cause of the condition.

What Is Known About The Genetics Of Weaver Syndrome?

The genetics of WS is not fully clear. It has been shown that mutations in a gene that is referred to as NSD1 can be causative of WS and, more specifically, that even a mutation to one copy of a person’s two NSD1 genes is sufficient to cause WS. It also has been demonstrated that some WS sufferers do not have any mutations in either one of their two NSD1 genes. The specific cause of WS in this latter group of individuals, whether genetic or otherwise, remains to be determined.

In healthy individuals, the NSD1 gene encodes a protein, formally known as “nuclear receptor binding protein 1”, that is comprised of 2596 amino acid molecules and that plays a yet-to-be-determined function in the nuclei of cells. However, it is known that this protein is highly active in cells of a large number of organs, including the brain, spleen, thymus, kidney, muscle, and lungs, for example. It is speculated that the protein encoded by NSD1 regulates the activity of one or more genes that are required for normal growth and development of these organs. Work is underway to definitively determine whether this is true.

More About The NSD1 Gene

It turns out that the NSD1 gene is a very interesting gene. Not only do some NSD1 gene mutations cause WS, but it is also known that certain mutations in NSD1 cause Sotos Syndrome, which is a growth and developmental disorder that leads to similar symptoms to those that are seen in WS, but which is a disorder that is distinct from WS. Further, some NSD1 mutations have been shown to cause some cases of childhood acute myeloid leukemia, which is a cancer of the blood. It is possible that future study of the NSD1 gene will reveal other conditions that can be caused by NSD1 gene mutations, and perhaps even a cure for WS, Sotos Syndrome, and those instances of childhood acute myeloid leukemia that are caused by mutations in NSD1.


Genetics Home Reference, National Institutes of Health, NSD1: https://ghr.nlm.nih.gov/gene/NSD1

J. Douglas et al., NSD1 Mutations Are The Major Cause Of Sotos Syndrome And Occur In Some Cases Of Weaver Syndrome But Are Rare In Other Overgrowth Phenotypes, American Journal of Human Genetics 72:132-143 (2002). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC378618/?tool=pubmed

T. R. P. Cole et al. Weaver syndrome, Journal of Medical Genetics: 29:332-337 (1992). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1015954/pdf/jmedgene00019-0046.pdf