Is Costello Syndrome hereditary?

Costello syndrome is a rare genetic condition that is almost exclusively caused by a de novo (spontaneous) mutation, meaning it is typically not inherited from the parents. While it is a genetic disorder, it is rarely hereditary, as most individuals with Costello syndrome are the first in their family to have the condition.

Is Costello syndrome an inherited condition?

Although Costello syndrome is a genetic disorder, it is rarely hereditary. It is caused by a germline mutation in the HRAS gene. In the vast majority of cases, this mutation occurs spontaneously in the egg or sperm cell at the time of conception, rather than being passed down from a parent. Because of this, the risk of parents who have one child with Costello syndrome having another child with the same condition is typically less than 1%.

How is Costello syndrome diagnosed genetically?

Diagnosis of Costello syndrome is confirmed through molecular genetic testing that analyzes the HRAS gene. Because the clinical features can overlap with other RASopathies, genetic testing is the gold standard for confirmation. If a child is suspected of having Costello syndrome, a clinical geneticist will typically order a targeted HRAS mutation analysis or a broader multigene panel.

What are the implications for family planning?

Genetic counseling is highly recommended for families affected by Costello syndrome to understand the recurrence risks and available options. Because most cases are de novo, the likelihood of a parent passing the condition to future offspring is very low; however, reproductive options include:

• Prenatal diagnosis: Amniocentesis or chorionic villus sampling (CVS) can be performed if a specific HRAS mutation has been identified in the child.


• Preimplantation Genetic Testing (PGT): For families who have previously had a child with Costello syndrome, PGT can be used in conjunction with IVF to screen embryos.


• Parental testing: Testing parents for mosaicism—a condition where a small percentage of body cells carry the mutation—can provide a more accurate assessment of recurrence risk.

Next steps

• Consult with a board-certified clinical geneticist to discuss testing and recurrence risks.


• Connect with the 13 members of the Costello syndrome community on DiseaseMaps.org to share experiences and resources.


• Review updated clinical guidelines provided by the Costello Syndrome Family Network.

Medical disclaimer: This information is for educational purposes only and should not replace professional medical advice, diagnosis, or treatment.

References

• NIH Genetic and Rare Diseases Information Center (GARD): Costello Syndrome


• Orphanet: Costello Syndrome (ORPHA:209)


• OMIM (Online Mendelian Inheritance in Man): HRAS gene and Costello syndrome (#218040)


• Costello Syndrome Family Network (CSFN)