Robinow Syndrome: What Is It And What Is Known About Its Underlying Genetics Causes?

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What Is Robinow Syndrome?

Robinow Syndrome (RS) is a genetic disorder that causes malformation of bone structure, among other defects, throughout the body in affected individuals. RS is divided into two categories: autosomal recessive RS and autosomal dominant RS. The autosomal recessive form of RS is generally characterized by the following defects:

  • Malformed bones of the spine (hemivertebrae)
  • Abnormal curvature of the backbone (kyphoscoliosis)
  • Diminutive fingers and toes (brachydactyly)
  • Diminutive arms and legs
  • Abnormal rib number (greater or less than 24, which is the number present in a healthy individual)
  • Two or more fused ribs
  • Shortness (in height)
  • Kidney defects
  • Heart abnormalities
  • Underdevloped genitals
  • Cranial and facial defects, such as widely spaced eyes, large forehead, and wide nose, for example
  • Tooth and gum problems

Few individuals who have the autosomal recessive form of RS have all of these defects, as most such individuals only have a subset of them. Further, the autosomal recessive form of RS is extremely rare, and is actually one of the rarest genetic disorders known to man. In fact, it is thought that perhaps only 200 or so people worldwide have the autosomal recessive form.

The commonly seen defects of the autosomal form of RS are mostly similar in substance to those of the autosomal recessive form. However, the typical defects of the autosomal dominant form are generally milder in severity than are the defects that are typical of the autosomal recessive form. Further, few people who have the dominant form have an abnormal number of ribs or any spine-associated defects.

What Is Known About The Underlying Genetic Causes Of The Two Forms Of Robinow Syndrome?

The autosomal recessive form of RS is characterized by one or more mutations in both copies of a single gene on human chromosome 9, which is designated ROR2 and is otherwise known as the receptor tyrokinase-like orphan receptor 2 gene. In individuals who do not have any mutations in ROR2, the ROR2 gene encodes a fully functional protein that is involved in complex chemical signaling events in cells. Molecular geneticists have postulated that normally functioning ROR2 protein has one or more critical roles in the body that take place sometime before birth (i.e., at the fetal stage of development). According to this theory, these critical roles are necessary for normal formation of the skeleton, kidneys, heart, and genital organs to occur. Mutations to the ROR2 gene therefore cause no or abnormal ROR2 to be synthesized. When ROR2 is not made or is defective, such as in the case in individuals having the autosomal recessive form of RS, proper formation of these body parts cannot occur and therefore defects arise.

Unfortunately, the underlying cause of the autosomal dominant form of RS remains unknown. Molecular geneticists have ruled out mutations in ROR2 as being the culprit. Instead, they believe that a yet-to-be-identified gene on human chromosome 1, when mutated, is responsible for causing the defects that are characteristics of the autosomal dominant form. Work towards positively identifying this gene are on-going.

There are no effective methods or drugs for treating either form of RS. It is hoped, however, that effective treatment methods will emerge as more becomes known about the normal activities of the ROR2 gene and the yet-to-be-identified other gene in the body.


Genetics Home Reference, National Institutes of Health, Robinow Syndrome:

Genetics Home Reference, National Institutes of Health, ROR2:

Robinow Syndrome Foundation, General Information: