Costello syndrome: Causes, symptoms, and treatment

Costello syndrome is rare, complex, and (for families) often exhaustingnot because people with Costello syndrome lack strength, but because the condition can
ask for attention from nearly every body system. If genetics had a “group chat,” Costello syndrome would be the one that keeps lighting up your phone:
heart check-ins, feeding support, therapy appointments, and the occasional “wait, is that normal?” question.

The good news: while there’s no single cure, there is a lot that can be done. With coordinated care and the right surveillance, many children and
adults with Costello syndrome make meaningful developmental progress, participate in school and community life, and build routines that feel less like a
medical marathon and more like… life.

What is Costello syndrome?

Costello syndrome is a genetic condition that affects growth and development and can involve the heart, skin, bones and joints, the nervous system, and
other organs. It’s part of a family of conditions called RASopathies, which are caused by changes in genes that influence the RAS/MAPK
signaling pathwaya pathway that helps regulate how cells grow, divide, and specialize.

Because that pathway is involved in cell growth, Costello syndrome is also associated with a higher risk of certain benign growths (like papillomas) and
specific cancers, particularly in childhood and adolescence. That can sound scaryunderstandablybut it’s also why doctors take a proactive, “screen early
and sensibly” approach.

Causes and genetics: when the body’s “growth switch” runs a little too hot

Costello syndrome is most commonly caused by a change (pathogenic variant) in the HRAS gene. HRAS provides instructions for making a
protein that acts like a molecular on/off switch in the RAS/MAPK pathway. In Costello syndrome, that switch is more “on” than it should be, nudging cells
to grow and divide more than usual. Think of it like a dimmer knob that got bumped brighter and won’t quite return to the original setting.

Is it inherited?

Costello syndrome follows an autosomal dominant inheritance pattern (one changed copy of the gene can cause the condition). However, most
cases happen de novomeaning the gene change occurs for the first time in the child, and there’s no prior family history.

Genetic counseling is still valuable. Even when neither parent has the variant detected in blood testing, a small recurrence risk can remain because of the
possibility of germline mosaicism (a situation where some reproductive cells carry the variant).

Symptoms: how Costello syndrome can show up (and change) over time

Costello syndrome doesn’t present as one single “look” or one predictable timeline. Two children can share the same diagnosis and still have very different
day-to-day needs. That said, there are common patterns doctors watch forespecially in infancy and early childhood.

Before birth and in newborns

• Prenatal ultrasound findings can include increased nuchal thickness and polyhydramnios (extra amniotic fluid).
• Fetal or newborn fast heart rhythms may occur in some cases.
• Feeding difficulties may begin early and can be severe enough to affect weight gain.
• Low blood sugar (neonatal hypoglycemia) may require monitoring in the newborn period.

Growth, feeding, and GI issues

Feeding difficulties are among the most common and challenging early issues. Low muscle tone (hypotonia), reflux, and coordination differences can make
eating hard work. Some infants require temporary or long-term tube feeding (nasogastric tube or gastrostomy tube). Reflux can be significant, and in some
situations doctors consider procedures like fundoplication based on severity and safety.

Growth patterns can be distinctive: some babies are larger than average at birth, but then gain weight more slowly afterward. Short stature is common, and
some individuals may have reduced growth hormone levels. Decisions about growth-related therapies are individualized and typically coordinated with
endocrinology and genetics.

Facial features, skin, and hair

Many people with Costello syndrome have recognizable facial features that can evolve with age (for example: fuller lips, full cheeks, and a prominent
forehead). Skin may feel soft and loose, especially on the hands and feet, and deep creases on palms and soles are common. Hair may be fine, sparse, or
curly.

Papillomassmall wart-like growthsoften appear around the nose and mouth or in the perianal region, typically later in childhood rather
than in infancy. They’re usually benign but can be bothersome and sometimes need removal.

Heart and blood vessel concerns

Cardiac issues are common, so heart monitoring isn’t optionalit’s a core part of care. The main concerns include:

• Hypertrophic cardiomyopathy (HCM): thickening of the heart muscle that can affect function and rhythm.
• Congenital heart defects, especially pulmonic valve stenosis.
• Arrhythmias, including supraventricular tachycardia and distinctive atrial rhythm issues in some individuals.

A practical takeaway: families often learn to recognize symptoms that deserve quick attentionunusual fatigue, fainting, chest pain, breathing trouble,
persistent palpitations, or “something is just off” episodesbecause arrhythmias can be intermittent.

Brain, nerves, and development

Developmental delay is common, but it’s also an area where early support can make a real difference. Many children benefit from physical therapy,
occupational therapy, speech therapy, and developmental interventions starting in infancy or toddlerhood.

Neurologic findings may include hypotonia, seizures in some individuals, and structural differences such as Chiari I malformation, which
can develop over time and may require neurosurgical evaluation depending on symptoms.

Bones, joints, and movement

Joint laxity, low muscle mass, and orthopedic differences can affect posture, gait, and fine motor skills. Common issues include ulnar deviation of wrists
and fingers, tight Achilles tendons (sometimes requiring bracing or surgical lengthening), kyphoscoliosis, hip dysplasia, and chest wall shape differences
(pectus carinatum or excavatum).

Vision, hearing, and dental considerations

Vision differences (like myopia, hyperopia, or strabismus) and hearing loss can occur. Dental crowding and other dental issues may also be present. Routine
screening helps avoid “hidden obstacles” that can look like learning or behavior challenges when the real issue is hearing, vision, or oral discomfort.

Tumors and cancer risk

Costello syndrome is associated with both benign tumors (such as papillomas) and an increased risk of certain malignancies. The cancers most often
discussed in this condition include rhabdomyosarcoma and neuroblastoma in young children, and bladder cancer
(transitional cell carcinoma) reported in adolescents and young adults.

It’s important to keep this in perspective: increased risk does not mean “inevitable.” It means surveillance is planned so that if something develops, it’s
caught earlywhen treatment is typically most effective.

How doctors diagnose Costello syndrome

Diagnosis usually begins with clinical suspicion based on features like feeding difficulties with failure to thrive, characteristic facial and skin findings,
hypotonia, and especially cardiac findings. The diagnosis is confirmed with molecular genetic testing showing a pathogenic variant in
HRAS.

Because features overlap with other RASopathies (particularly Noonan syndrome and cardiofaciocutaneous syndrome), many clinicians use a multigene panel for
RASopathy-related genes, or broader testing when needed. Getting the correct genetic diagnosis matters because it guides surveillance and helps families
anticipate likely needs.

Treatment and management: no cure, but a very real game plan

There’s currently no single cure for Costello syndrome, so treatment focuses on managing symptoms, preventing complications, and supporting development.
Most people do best with a multidisciplinary teamoften including genetics, cardiology, gastroenterology, nutrition, neurology, orthopedics, dermatology,
endocrinology, ophthalmology, audiology, speech therapy, OT/PT, and educational specialists.

Feeding and growth support

• Feeding therapy to improve coordination, safety, and tolerance.
• Reflux management (positioning strategies, medications, and in some cases surgery).
• Tube feeding (NG or G-tube) when oral intake isn’t enough for safe growth.
• Nutrition planning to balance calories, protein, hydration, and micronutrients.

A small but important detail: feeding challenges often affect the whole household’s rhythm. Practical supportslike a consistent plan, clear targets, and a
“what counts as a win today?” mindsetcan reduce stress while still keeping care effective.

Cardiac care

Cardiac evaluation typically includes an echocardiogram and ECG at diagnosis, with follow-up determined by findings and age. Holter monitoring may be used
to detect intermittent arrhythmias. Treatment depends on the specific issuestandard cardiology protocols are used for HCM, valve disease, and rhythm
disturbances.

In select situations, targeted therapies are being explored or used under specialist guidance. For example, a MEK inhibitor (trametinib) has been reported
as a treatment option for hypertrophic cardiomyopathy with heart failure that does not respond to standard therapy. This is specialized care and not a
routine approach, but it’s part of why experienced centers matter.

Another practical point: general anesthesia can carry added risk in some individuals with Costello syndromeespecially with significant cardiomyopathy or
certain atrial arrhythmiasso anesthesiology teams typically plan carefully and coordinate with cardiology.

Development, communication, and school supports

• Early intervention services (often starting in infancy).
• Speech and language therapy, including support for expressive language and clarity.
• Occupational therapy for fine motor skills, feeding, sensory needs, and daily living tasks.
• Physical therapy for strength, coordination, gait, endurance, and joint stability.
• School supports such as an IEP or 504 plan, tailored to learning style and attention needs.

“Treatment” here isn’t about changing who a child isit’s about giving them tools. Many children with Costello syndrome are described as social and
engaging, and strong communication support helps that personality shine without frustration stealing the spotlight.

Orthopedic and mobility care

Management may include bracing for ulnar deviation, supportive footwear or orthotics, and monitoring for scoliosis or hip issues. Tight Achilles tendons can
improve with stretching, bracing, and therapy; some individuals require surgical lengthening. The goal is comfort, function, and injury preventionnot
forcing a “perfect” posture.

Skin care and papillomas

Dry or thickened skin may benefit from routine moisturizing and keratolytic products as advised by dermatology. Papillomas can be treated if painful,
infected, bleeding, or socially distressing. Removal methods are chosen based on location and recurrence risk.

Tumor surveillance: proactive, not panicked

Surveillance plans vary by clinician and individual history, but commonly discussed approaches include:

• Abdominal and pelvic ultrasound every 3 to 6 months in early childhood (often until about age 8 to 10)
  to screen for rhabdomyosarcoma and neuroblastoma.
• Annual urinalysis starting around age 10 to look for blood in the urine as a screening step related to bladder cancer risk.
• Regular physical exams with attention to new lumps, persistent pain, or unexplained symptoms.

If you’re thinking, “That’s a lot,” you’re not wrong. But many families find surveillance becomes routinelike oil changes for a car you love and plan to
keep for a long time. You do it because it helps you stay ahead of problems, not because you expect disaster every week.

Other routine check-ins

• Vision and hearing screening at recommended intervals.
• Neurologic monitoring for symptoms suggesting Chiari malformation, seizures, or sleep-related breathing issues.
• Endocrine evaluation when growth patterns suggest hormone concerns.
• GI follow-up for reflux, constipation, feeding tolerance, and nutrition.

What’s the outlook?

Prognosis varies widely and often depends on cardiac involvement and the severity of early feeding and respiratory issues. Some individuals have complex
medical needs throughout life; others stabilize over time with supportive care. Developmental outcomes also vary, but many children continue to gain skills,
especially when therapies are started early and adjusted as needs evolve.

A realistic and hopeful framing is this: Costello syndrome usually means a longer care “to-do list,” but it doesn’t erase joy, personality, relationships,
or learning. It changes the routenot the fact that a meaningful journey is still possible.

When to call your clinician urgently

Always follow your care team’s guidance, but urgent evaluation is typically warranted if any of the following occur:

• Fainting, chest pain, new shortness of breath, or persistent palpitations
• Signs of heart failure (worsening breathing, swelling, severe fatigue, poor feeding)
• Repeated vomiting, dehydration, or inability to keep down feeds
• A new or rapidly growing lump, unexplained bruising, or persistent bone/muscle pain
• Blood in the urine or urinary symptoms that are unusual or persistent
• Neurologic changes (new severe headaches, weakness, seizures, or loss of coordination)

Real-life experiences: the parts you don’t see on the lab report (added 500+ words)

Medical summaries tend to read like a checklistheart, skin, bones, developmentwhile real life feels more like a series of tiny decisions made on busy
weekdays. Families often describe the early months as a “diagnostic odyssey,” where they can sense something is different but don’t yet have a name for it.
Feeding struggles are frequently the first big challenge: you’re not just feeding a baby, you’re negotiating with reflux, low tone, fatigue, and a schedule
that sometimes makes every ounce feel like a victory. Many parents say they had to redefine success. A “good day” might be a comfortable feed, a stable
weight check, or simply fewer tearsbaby’s and theirs.

Once the diagnosis is confirmed, the emotional tone often shifts. There’s grief (because no one dreams of medical complexity), but there’s also relief.
Relief has a practical side: having a diagnosis can unlock specialists who actually recognize the pattern, therapists who know what to prioritize, and a
surveillance plan that transforms vague worry into a clear next step. Families frequently mention that learning the “why” behind the screenings helps.
Instead of feeling like you’re constantly hunting for problems, you begin to see monitoring as a way to protect your child’s future options.

Therapies become part of the rhythm of home life. PT might look like play on the living room floor with purposeful stretches mixed into giggles. OT can
involve creative hacksgrips, supports, adaptive utensilsthat turn frustration into independence. Speech therapy is often a long game, and many caregivers
learn to celebrate communication in all forms: gestures, signs, devices, approximations, and eventually words. Teachers and therapists who “get it” can make
school feel less like a performance and more like a place where a child is genuinely understood.

Families also talk about the social side: kids with Costello syndrome are often described as friendly and engaged, but fatigue or motor challenges can make
typical activities harder. Parents become expert event plannerschoosing playdates that won’t drain energy reserves, advocating for inclusion without pushing
a child past their limits, and teaching others that accommodations aren’t “special treatment,” they’re access. Over time, siblings often develop a quiet
competency that shows up in surprising ways: empathy, patience, and a strong sense of teamwork.

The most repeated lesson families share is that support networks matter. Connecting with a rare disease community can turn isolation into practical wisdom:
which questions to ask cardiology, how to prepare for anesthesia, how to track symptoms without spiraling, and how to explain the condition to relatives in
one calm paragraph. Many caregivers also emphasize taking care of themselvesbecause the most sustainable care plan includes the caregiver’s health too.
Respite, mental health support, and small routines that are not medical (a walk, a hobby, a normal dinner) can keep the whole system functioning.

Finally, as children grow, families often shift from “survive the appointments” to “build the life.” That may include focusing on strengths, supporting
friendships, and planning transitions to adolescent and adult care. Costello syndrome can be a demanding companion, but many families describe their child
not as a diagnosis, but as a person with a distinctive sparkone who teaches everyone around them how to measure progress in meaningful, human ways.

Conclusion

Costello syndrome is caused most often by a pathogenic variant in the HRAS gene and can affect multiple body systems, especially growth, development, skin,
and the heart. Symptoms often begin earlyfeeding difficulties, hypotonia, and cardiac findings are commonwhile other features (like papillomas and certain
tumor risks) may appear later. Treatment focuses on proactive, team-based management: supporting nutrition and growth, monitoring and treating cardiac
issues, providing early developmental therapies, addressing orthopedic concerns, and following recommended tumor surveillance. With coordinated care and
informed support, many individuals and families build stable routines and meaningful quality of life.

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