Aarskog syndrome
Inheritance
How is Aarskog syndrome inherited?
Aarskog syndrome is typically inherited in an X-linked pattern. The 'X' chromosome is a sex chromosome. The 'Y' chromosome is the other sex chromosome. Males usually have one X chromosome and one Y chromosome. Females usually have two X chromosomes. The FGD1 gene for Aarskog syndrome is located on the X chromosome. Because males only have one X chromosome and therefore one FGD1 gene, if this gene has a mutation, the male is affected with Aarskog syndrome. Because females have two X chromosomes, if one of their FGD1 genes has a mutation, they are known as heteozygotes and may not have symptoms of Aarskog. However, some female heterozygotes of Aarskog syndrome have mild features of the condition.
Even though most cases of Aarskog syndrome are X-linked, in rare cases it can run in the family in a different ways, both autosomal dominant and recessive patterns of inheritance, but the genetic cause in these cases currently remains unknown.
It is important to take into account family history when discussing inheritance patterns. A genetic counselor or medical geneticist can help determine the way the condition is being passed down in a particular family. A medical geneticists can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website. Genetic counselors can be found on the National Society of Genetic Counselors website.
References
- Xu, M., Qi, M., Zhou, H., Qui, H., et al. (2010). Familial syndrome resembling Aarskog syndrome. American Journal of Medical Genetics. Part A, 152A, 2017?2022. PMID: 20607856
More Inheritance Content
What does it mean to have inherited a variant in the gene for Aarskog syndrome?
Can my child still have Aarskog syndrome without having a FGD1 gene mutation?
If a male is affected with Aarskog syndrome, what is the chance that his children will be affected?
If a female is a carrier of Aarskog syndrome, what is the chance that her children will be affected?
What does it mean to have inherited a variant in the gene for Aarskog syndrome?
When a person inherits a change or variant of uncertain significance (VUS or VOUS) in the FGD1 gene for Aarskog syndrome, it means they have a change in the gene but it is currently not known if this change actually causes Aarskog syndrome. Sometimes the interpretation of variants change as more people are tested and more data is received by the laboratory.
References
- http://ghr.nlm.nih.gov/glossary=allelicvariantofunknownsignificance
- Orrico A, Galli L, Faivre L, Clayton-Smith J, Azzarello-Burri SM, Hertz JM, Jacquemont S, Taurisano R, Arroyo Carrera I, Tarantino E, Devriendt K, Melis D, Thelle T, Meinhardt U, Sorrentino V. 2010. Aarskog-Scott syndrome: Clinical update and report of nine novel mutations of the FGD1 gene. American Journal of Medical Genetics Part A 152A: 313?318. PubMed ID: 20082460
- Schwartz CE, Gillessen-Kaesbach G, May M, Cappa M, Gorski J, Steindl K, Neri G. 2000. Two novel mutations confirm FGD1 is responsible for the Aarskog syndrome. Eur. J. Hum. Genet. 8: 869?874. PubMed ID: 11093277
Can my child still have Aarskog syndrome without having a FGD1 gene mutation?
Your child can still have Aarskog syndrome without having a FGD1 gene mutation. Only about 20% of people with Aarskog syndrome have a FGD1 gene mutation. Many people receive a clinical diagnosis if they have many of the clinical features of Aarskog syndrome but genetic testing was negative.
If a male child is found to have a FGD1 gene mutation for Aarskog syndrome, is his mother then always found to be a carrier?
There is always the chance for a new gene change or mutation in a boy with Aarskog syndrome, although it is rare. There has also been one reported case of two fraternal twin brothers with the same FGD1 gene mutation and a genetic diagnosis of Aarskog syndrome. The mother had genetic testing on her blood and was not found to have the FGD1 gene mutation. This finding suggests that some of the mother's sex cells (eggs) have the mutation, but not all. Because of this, it was unable to be detected through a blood draw. The term for this is called "germline mosaicism." The recurrence risk for future pregnancies is therefore not as high, but higher than the general population.
References
- Pilozzi-Edmonds L, et al. Fraternal twins with Aarskog-Scott syndrome due to maternal germline mosaicism. Am J Med Genet A. 2011 Aug;155A(8):1987-90. doi: 10.1002/ajmg.a.34094. Epub 2011 Jul 7.
If a male is affected with Aarskog syndrome, what is the chance that his children will be affected?
If a male is affected with X-linked Aarskog syndrome, there is a 0% chance that his male children will be affected (because males pass on their Y sex chromosome to their male children), and a 100% chance that his female children will get the gene change (because males pass on their X chromosome to their female children).
If a male has Aarksog syndrome caused by an unknown gene change, he may have up to a 50% chance to pass on Aarskog syndrome to each of his children (boys or girls). A genetic counselor or medical geneticist can help determine the likelihood that a person with Aarskog pass on the condition. A medical geneticists can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website. Genetic counselors can be found on the National Society of Genetic Counselors website.
If a female is a carrier of Aarskog syndrome, what is the chance that her children will be affected?
If a female is an unaffected carrier or has the X-linked form of Aarskog syndrome, there is 50% chance that each male child will be affected with Aarskog syndrome, and there is a 50% chance that each female child will be a carrier of Aarskog syndrome. Overall, in each pregnancy,there is a 25% chance to have an affected male, 25% chance to not have an affected male, 25% chance to have a female who is a carrier, 25% chance to have a female who is not a carrier.
If a female has Aarksog syndrome caused by an unknown gene change, she may have up to a 50% chance to pass on Aarskog syndrome to each of her children (boys or girls). A genetic counselor or medical geneticist can help determine the likelihood that a person with Aarskog pass on the condition. A medical geneticists can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website. Genetic counselors can be found on the National Society of Genetic Counselors website.
