Short answer · Medically reviewed summary · Last updated: 2026-05-08
Costello Syndrome is primarily diagnosed through clinical evaluation by a medical geneticist followed by molecular genetic testing to identify a pathogenic variant in the HRAS gene. Because Costello Syndrome is a rare multi-system disorder, confirmation often requires a multidisciplinary approach to distinguish it from other RASopathies. How is Costello Syndrome diagnosed clinically? The diagnostic process for Costello Syndrome usually begins when a pediatrician or specialist notices a specific pattern of physical features, such as macrocephaly, coarse facial features, and failure to thrive in infancy.
How is Costello Syndrome diagnosed?
How Costello Syndrome is diagnosed: tests, specialists and the diagnostic journey, told by patients and reviewed against medical sources.
Costello Syndrome is primarily diagnosed through clinical evaluation by a medical geneticist followed by molecular genetic testing to identify a pathogenic variant in the HRAS gene. Because Costello Syndrome is a rare multi-system disorder, confirmation often requires a multidisciplinary approach to distinguish it from other RASopathies.
How is Costello Syndrome diagnosed clinically?
The diagnostic process for Costello Syndrome usually begins when a pediatrician or specialist notices a specific pattern of physical features, such as macrocephaly, coarse facial features, and failure to thrive in infancy. Because Costello Syndrome presents with complex symptoms, clinicians often start with a physical examination and a detailed developmental history. Diagnosis is confirmed by identifying a germline mutation in the HRAS gene, which is present in approximately 80-90% of individuals with the clinical features of Costello Syndrome.
Which specialists are involved in the diagnostic process?
Due to the complexity of Costello Syndrome, the diagnosis is typically made by a clinical geneticist. However, the diagnostic journey often involves a "diagnostic odyssey" where families see multiple specialists before reaching a conclusion. You may be referred to the following experts:
- Clinical Geneticists: To oversee genetic testing and confirm the diagnosis.
- Pediatric Cardiologists: To screen for hypertrophic cardiomyopathy, a common feature.
- Endocrinologists: To assess growth hormone deficiency.
- Dermatologists: To evaluate characteristic skin findings like papillomata.
What conditions are in the differential diagnosis?
Costello Syndrome is often confused with other RASopathies due to overlapping clinical features. Key conditions to rule out include:
- Noonan Syndrome
- Cardiofaciocutaneous (CFC) Syndrome
- Beckwith-Wiedemann Syndrome
We understand the immense frustration that comes with a long diagnostic journey; please know that your observations as a caregiver are valid and vital to the clinical assessment.
Next steps
- Consult a board-certified clinical geneticist to discuss HRAS mutation testing.
- Request a referral to a center specializing in RASopathies or rare genetic disorders.
- Connect with the 13 members currently sharing their experiences with Costello Syndrome on DiseaseMaps.org to find support.
- Keep a detailed medical journal of your child’s developmental milestones and physical symptoms to share with your care team.
Medical disclaimer: This information is for educational purposes only and does 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): #218040
- Costello Syndrome Family Network
