Costello syndrome is a rare genetic condition caused by a pathogenic variant in the HRAS gene. It belongs to a group of conditions called RASopathies, which also includes Noonan syndrome, all caused by mutations affecting the same cell-signaling pathway. People with Costello syndrome typically have distinctive facial features, slow growth after birth despite high birth weight, heart differences, loose and stretchable skin, and an increased risk of certain tumors that requires lifelong cancer surveillance. For decades, Costello syndrome was broadly described as causing mild to moderate intellectual disability alongside an unusually warm, sociable personality. A 2026 case series using detailed neuropsychological testing found a far wider range of cognitive functioning than this description suggests, from extremely low to superior, underscoring the need for individualized assessment rather than assumptions based on the diagnosis alone.
What Causes Costello Syndrome
Costello syndrome is caused by a pathogenic variant in HRAS, a gene that codes for a protein central to the RAS/MAPK pathway, a chain of signals inside cells that controls how they grow, divide, mature, and survive. Almost all cases arise from a new, non-inherited variant in this single gene, most often affecting the same small region of the protein. Because the RAS/MAPK pathway also underlies Noonan syndrome, caused by variants in related genes such as PTPN11, SOS1, and RAF1, the two conditions share overlapping features, including short stature, heart differences, and distinctive facial characteristics, and are grouped together with several other conditions as RASopathies. However, HRAS variants in Costello syndrome tend to produce stronger overactivation of the pathway than most Noonan-causing variants, which helps explain why Costello syndrome carries a more pronounced risk of certain solid tumors and more severe cardiac involvement, including a higher likelihood of hypertrophic cardiomyopathy, a thickening of the heart muscle that remains a leading contributor to illness and, in some infants, death.
Living With Costello Syndrome: What Helps
- Get a thorough, individualized cognitive and behavioral assessment. Recent testing of people with Costello syndrome found functioning ranging from extremely low to superior; relying on general descriptions of the condition rather than direct assessment can lead to mismatched expectations and support.
- Watch for anxiety as a common thread across RASopathies. Caregivers and young adults with RASopathies, including Costello syndrome, consistently describe anxiety as one of the most frequent mental health concerns, often appearing alongside attention, executive functioning, and social difficulties.
- Expect mental health symptoms to interact with physical health. Families report that mood and behavior often shift alongside physical symptoms such as pain, fatigue, or cardiac concerns, so addressing physical health can be an important part of supporting emotional wellbeing.
- Seek providers with rare disease experience, and advocate when needed. A lack of provider knowledge about RASopathies and poor access to appropriate mental health services are commonly reported barriers; families often need to take an active advocacy role to get appropriate care.
- Stay attached to routine cancer and cardiac surveillance. Because Costello syndrome carries increased risks of certain tumors and heart differences, consistent medical monitoring supports both physical health and the peace of mind that comes with catching concerns early.
A Closer Look: A Wider Neurobehavioral Range Than Once Assumed
A 2026 case series examined three unrelated individuals with Costello syndrome, each with a different pathogenic HRAS variant, using detailed neuropsychological testing. Rather than finding the uniform mild to moderate cognitive impairment often described in older literature, the researchers documented a wide range of functioning across the three individuals, spanning from extremely low to superior. The study also reported the first cognitive testing results for a person with a specific HRAS variant known as c.179G>A, p.Gly60Asp, adding new data to a still-small body of evidence. Alongside cognitive testing, the researchers gathered patient-reported outcomes covering social functioning, emotional wellbeing, and quality of life. The authors concluded that flexible, individualized neurobehavioral assessment methods are essential for Costello syndrome. They noted that above-average cognitive functioning is possible and should not be overlooked. Quality of life and mental health, the authors added, deserve attention as core outcomes rather than secondary concerns.
Mental Health Care Access Across RASopathies
A 2026 qualitative study explored the mental health care experiences of families affected by RASopathies, the group of conditions that includes Costello syndrome and Noonan syndrome. Researchers analyzed four virtual focus groups involving 21 caregivers of youth with RASopathies, alongside individual interviews with 11 young adults who have a RASopathy themselves. Across these conversations, anxiety stood out as a particularly frequent concern, appearing alongside attention and executive functioning difficulties, mood changes, and social challenges. Participants described mental health symptoms that often interfaced with physical health symptoms, making the two difficult to address separately. Families also identified consistent barriers to care, including services that were hard to access, medications with adverse effects, and providers who lacked experience or knowledge of RASopathies. Many caregivers and patients reported that getting appropriate support required significant personal advocacy. The study's authors concluded that improving care will require targeted provider training on rare diseases. They also called for trauma-informed approaches and greater community awareness of RASopathies as a group.
Practical Tips for Families and Caregivers
- Don't assume a cognitive ceiling based on the diagnosis alone. Because documented functioning in Costello syndrome ranges so widely, request assessments that can detect above-average as well as below-average ability, and set expectations accordingly.
- Bring up anxiety proactively, even if it isn't the presenting concern. Anxiety is one of the most consistently reported mental health issues across RASopathies; mentioning it directly can help ensure it gets addressed rather than overlooked alongside more visible medical needs.
- Track connections between physical symptoms and mood or behavior. Pain, fatigue, cardiac symptoms, and other physical changes may show up as shifts in behavior; keeping notes on timing can help your care team see patterns that are easy to miss in short appointments.
- Seek out providers or centers with RASopathy-specific experience. Because general providers often lack familiarity with these rare conditions, specialized clinics or condition-specific organizations can offer more informed guidance and reduce the burden of advocacy on families.
- Keep cancer and cardiac surveillance on schedule. Routine monitoring for tumors and heart differences is a core part of care in Costello syndrome; staying current with this surveillance protects physical health and can ease anxiety tied to uncertainty.