All About Aarskog-Scott Syndrome And Its Genetic Cause

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What Is Aarskog-Scott Syndrome?

Aarskog-Scott Syndrome is a genetically-caused disorder in which any given affected individual suffers from one or more of a wide range of defects. These defects include:

  • Facial development defects, such as a small nose, an abnormally wide space between the nose and upper lip and very widely spaced eyes
  • Cleft lip and cleft palate
  • Short height relative to peers in childhood (but usually not adulthood)
  • Hand defects, such as short fingers, curved pinky fingers and the prescence of webbing between fingers
  • Heart defects
  • Genital abnormalities, such as undescended testes and an abnormal scrotum
  • Reduced learning capacity
  • Behavioral problems

Most individuals who have Aarskog-Scott Syndrome are inflicted with only a few of these defects, which can range in severity. Indeed, many of these individuals have defects that are hardly noticeable. Only in the worst cases, which are rare, is severe incapacity or death observed.

What is Known About The Genetics Of Aarskog-Scott Syndrome?

Molecular biologists have determined that the genetic cause of Aarskog-Scott Syndrome is mutation of a gene that has been designated FGD1. In normal individuals, the FDG1 gene encodes a protein known as guanine nucleotide exchange factor. Guanine nucleotide exchange factor normally functions to regulate a second gene, designated CDC42, whose protein product is responsible for providing certain cellular signals that are needed during an individual’s embryonic development. In individuals who do not have a normal copy of the FGD1 gene, proper regulation of the CDC42 gene does not occur, which of course means that certain key cellular signals are not made during embryonic development. Absent these signals, developmental mistakes that lead to the aforementioned defects result.

Because the FGD1 gene is located on the X-chromosome (of which males have only one copy and women two), males are much more likely to be inflicted with Aarskog-Scott Syndrome than females.

How Is Aarskog-Scott Syndrome Diagnosed?

There are several laboratories worldwide that offer a genetic analysis service that is specific for Aarskog-Scott Syndrome. Typically, the person to be analyzed is either:

(1) an already-born individual or a fetus who is suspected of having Aarskog-Scott Syndrome; or

(2) a woman who, based on family history, is at risk of carrying a copy of a mutated version of the FGD1 gene (and therefore may be at risk of having a child affected by the disorder).

In such analysis, these laboratories obtain a body sample (such as saliva or blood) from the person who is to be tested and then, through a series of chemical events, determine on a nucleotide-by-nucleotide basis the sequence of the only, or each, copy of the individual’s FGD1 gene.

Once this analysis is complete, the results are sent to the individual’s health care provider. The provider then discusses the significance of the findings with the individual and/or individual’s kin. Oftentimes, the health care provider will work in conjunction with a genetic counselor in conveying this important diagnostic information and what it means to the individual.


A. Orrico et al., Aarskog-Scott Syndrome: Clinical Update and Report of Nine Novel Mutations of the FGD1 Gene, American Journal of Medical Genetics, 2010.

Genetics Home Reference, National Institutes of Health, Aarskog-Scott Syndrome:

Genetics Home Reference, National Institutes of Health, FGD1:

J.K. Bedoyan et al., First case of deletion of the faciogenital dysplasia 1 (FGD1) gene in a patient with Aarskog-Scott syndrome, European Journal of Medical Genetics, 2009.