Is Rett Syndrome Autosomal? - The Genetics of RS

What is Rett Syndrome?

Before understanding genetic questions such as is Rett syndrome autosomal or X-linked, you must first understand what Rett syndrome is and what it is not. The disorder most often appears in female children, although there are documented cases of male children with conditions that meet the diagnostic criteria. Unfortunately, few male embryos with this genetic disorder survive, so the vast majority of patients are female.

Rett syndrome (RS) mimics many of the same symptoms and developmental delays of autism spectrum disorders, although it is not a type of autism. Like regressive autism, female children later diagnosed with RS begin their development normally. Between the ages of 6-18 months, they start to lose skills such as language, coordination, and motor control of their hands. Growth, especially concerning head size, begins to slow, breathing abnormalities appear, and other symptoms present. This is due to mutations in the MECP2 or CDKL5 genes, which produce protein needed for healthy brain function and neurological development. Variations of RS, considered atypical Rett syndrome, do not have any periods of normal development or there are seizures in conjunction with classic symptoms.

The Genetics of Rett Syndrome

Two gene mutations are believed to cause Rett syndrome. The first, and most common, is a mutation of the MECP2 gene. Further research has demonstrated that a mutation of the CDKL5 gene is also present in many RS patients. Both of these genes reside in the X chromosome. Both genes are responsible for the production of certain types of proteins the brain needs for normal development. Mutations in these genes stop the production of these proteins, while causing other genes to function abnormally, resulting in atypical brain development and loss of abilities.

Since RS is tied to genes on the X chromosome, one of two chromosomes responsible for determining sex, it is classified as an X-linked genetic disorder. Autosomal genetic disorders, in contrast, have genetic abnormalities or mutations on non-sex related chromosomes. Therefore, the simple answer to the question is Rett Syndrome autosomal is no, since RS is directly linked to the mutation of genes on the X chromosome.

X-Linked Dominant Genetic Disorders & Heredity

Rett syndrome can be further described and classified as an X-linked dominant disorder. Dominant genetic disorders require only one copy of the affected gene, whereas recessive disorders require a copy from both parents. With regards to girls with Retts a mutated gene on only one X chromosome is all that is needed for the disorder to be present.

Research reveals that more than 99% of RS cases are the result of a new mutation and studies continue to determine exactly what causes these sporadic genetic errors. Less than 1% of RS patients have a parent with mutations in the MECP2 or CDKL5 gene.

In terms of heredity, it is estimated that parents with one daughter diagnosed with Rett syndrome have a less than 1% chance of a second daughter developing RS. Furthermore, statistics indicate that few girls of reproductive age with an RS diagnosis actually reproduce, further reducing the risk of genetically inheriting the required mutated genes.

References

Genetics Home Reference from National Institutes of Health https://ghr.nlm.nih.gov/handbook/inheritance/inheritancepatterns

International Rett Syndrome Foundation, What is Rett Syndrome? https://www.rettsyndrome.org/about-rett-syndrome/what-is-rett-syndrome-2.html