Costello syndrome is a rare genetic condition that affects growth, development, and several body systems. Features often include loose skin on hands and feet, feeding problems in infancy, slow growth, and delayed motor and speech milestones. Many people with Costello syndrome also have heart problems and distinctive facial features, and some develop tumors, so regular monitoring is important. It is lifelong and usually recognized in infancy or early childhood, and not everyone will have the same experience. Care focuses on supportive therapies, heart care, nutrition support, and cancer screening, and many living with Costello syndrome benefit from early intervention and coordinated specialist care.
Overview
Costello syndromeSymptoms
Early signs of Costello syndrome often appear at birth or in infancy: poor feeding, slow growth, loose skin, flexible joints, and distinctive facial features. Many children have developmental delays and low muscle tone. Heart problems and rhythm issues are common.
Outlook and prognosis
Many people with Costello syndrome grow and learn at their own pace, often needing ongoing therapies and check-ins with specialists. Heart care, feeding support, and help with movement can make daily life safer and more comfortable. With coordinated care, many reach school, jobs, and adulthood.
Causes and risk factors
Costello syndrome is caused by a change (mutation) in the HRAS gene, usually new (de novo) and autosomal dominant. Risk rises with an affected parent and is higher with older paternal age. It isn’t caused by pregnancy behaviors or environment.
Genetic influences
Genetics is central in Costello syndrome. Nearly all cases result from new (de novo) changes in the HRAS gene, which acts like a growth “dimmer switch” stuck too high. Inherited cases are rare, so recurrence risk is usually low but not zero.
Diagnosis
Doctors suspect Costello syndrome from clinical features—slow growth, loose skin, distinctive facial traits, and heart findings—then confirm with genetic tests for HRAS changes. The genetic diagnosis of Costello syndrome may be supported by imaging and heart evaluations.
Treatment and drugs
Treatment for Costello syndrome focuses on each person’s needs, often combining heart care, feeding and growth support, physical/occupational therapy, and learning services. Doctors monitor for tumors and adjust plans as children grow. Genetic and cardiology follow-up guide medications, surgeries, and supports.
Symptoms
Feeding challenges, slow growth, and developmental delays can be part of daily life for people with Costello syndrome. Parents often notice early features of Costello syndrome in the first months, such as trouble feeding and slow weight gain. Features vary from person to person and can change over time. Regular checkups help spot and manage heart, skin, and movement issues early.
Babies may have weak sucking, reflux, or frequent vomiting that make feeds long and tiring. In Costello syndrome, some need thickened feeds, high-calorie formulas, or a temporary feeding tube to support growth.
Height and weight often track below peers even with good nutrition. Many with Costello syndrome are shorter than expected in childhood and adulthood.
Full lips, a wide mouth, and a broad nasal bridge are common. These traits are harmless but can help doctors recognize the condition.
Skin may feel loose or soft with deep creases on the palms and soles, and hair can be sparse or curly. Small wart-like bumps near the nose or mouth (papillomas) can appear and sometimes get irritated.
How people usually first notice Costello syndrome?
Many families first notice signs of Costello syndrome in infancy when a baby has trouble feeding, gains weight slowly despite a good appetite, or seems unusually floppy due to low muscle tone. Doctors may spot features such as loose, soft skin with deep creases on the hands and feet, distinctive facial traits that become clearer over time, and delays in sitting, crawling, or walking; some babies also show heart findings like an enlarged heart or abnormal rhythm during early check-ups. Prenatal clues can include too much amniotic fluid (polyhydramnios) or poor growth on ultrasound, so when parents search for the first signs of Costello syndrome or ask how Costello syndrome is first noticed, these early growth, skin, facial, developmental, and cardiac patterns often prompt genetic evaluation.
Types of Costello syndrome
Costello syndrome has recognized clinical variants based on the specific HRAS gene change, which can shape how early symptoms appear and how strongly certain features show up. People may notice different sets of symptoms depending on their situation. Some variants lean toward more feeding, heart, and growth concerns in infancy, while others have milder courses or different timing of milestones. When people search for types of Costello syndrome, they’re usually asking about HRAS mutation–based variants, which can influence severity and risks over time.
G12S variant
Often linked with a comparatively milder course among HRAS changes. Many children still have feeding issues, loose skin, and delayed motor milestones. Heart thickening can occur but may be less severe than in other variants.
G12A variant
Tends to show classic Costello features with moderate severity. Early feeding problems and poor growth are common, along with joint laxity and soft skin. Heart involvement such as hypertrophic cardiomyopathy may appear in childhood.
G12V variant
Often associated with a more severe presentation. Babies may have significant feeding challenges, slower growth, and earlier heart thickening. Developmental delays can be more pronounced.
G12D variant
Generally linked to a moderate-to-severe course. Infants may show low muscle tone, reflux, and difficulty gaining weight. Heart changes and breathing issues can emerge earlier than average.
G12C variant
Reported with features that overlap the classic picture but vary in intensity. Feeding problems and delayed milestones are common, while heart findings range from mild to significant. Monitoring across childhood helps track evolving needs.
G13C variant
Often associated with a somewhat milder phenotype. Children may have fewer or later heart complications and make steadier developmental gains. Growth and feeding issues still need attention.
G13D variant
Can present with classic Costello features and variable heart involvement. Some children have better growth and muscle tone over time. Regular cardiac and developmental follow-up remains important.
p.T58I variant
Reported in a smaller number of people with features overlapping the classic form. Feeding and growth concerns are common, with variable heart thickening. Long-term outlook depends on individual monitoring and support.
What genetics can tell you about symptoms
Certain HRAS gene changes in Costello syndrome can lead to looser skin, deep palm and sole creases, and distinctive facial features, because HRAS signals cells to grow and mature. More activating HRAS variants often bring faster growth early on but greater feeding, heart, and tumor risks.
Causes and risk factors
Costello syndrome usually happens because of a new change in the HRAS gene. This change is typically not inherited, but it can rarely come from a parent who carries the change in only some cells. Older paternal age may slightly raise the chance of a new HRAS change, and everyday exposures do not cause this condition. Some risks are modifiable (things you can change), others are non-modifiable (things you can’t), and most here are not changeable. Family history or a known HRAS gene change can increase the chance of it happening again, so genetic counseling can help explain risk factors for Costello syndrome.
Environmental and biological risk factors
Costello syndrome is present from birth, so any risks start before or around conception. While early symptoms of Costello syndrome often appear in infancy, the likelihood of it occurring is shaped mostly by biology rather than day-to-day choices. Doctors often group risks into internal (biological) and external (environmental). Here’s what is known so far.
As men get older, age-related changes in sperm become more common and can slightly raise the chance of Costello syndrome. The increase appears gradual and is more noticeable at higher paternal ages.
A higher mother’s age has not shown a consistent link with Costello syndrome. Most pregnancies affected occur across a wide range of maternal ages.
No specific environmental exposure has been confirmed to increase the chance of Costello syndrome. Studies have not tied common pollutants or workplace exposures to higher risk so far.
No particular maternal medical condition has been shown to raise the likelihood of Costello syndrome. Usual pregnancy illnesses have not been linked to a higher chance.
Genetic risk factors
Changes in a gene called HRAS keep a growth signal switched on when it should be off in Costello syndrome. Most cases happen as a brand-new change in the child rather than being inherited from a parent. Risk is not destiny—it varies widely between individuals, and even the same HRAS change can look different from one person to another. This quick guide outlines the genetic causes of Costello syndrome and what they may mean for family risk.
HRAS gene changes: An activating change in the HRAS gene drives Costello syndrome by overstimulating cell growth signals. This single change is enough to cause the condition.
Dominant inheritance: Costello syndrome follows a dominant pattern, meaning one altered copy can cause symptoms. However, it is almost always not inherited because the change usually arises for the first time in the child.
De novo origin: In most families, the HRAS change is new in the child and not found in either parent. Many of these new changes start in the father’s sperm and become more likely with increasing paternal age.
Parental mosaicism: A parent can carry the HRAS change in a small fraction of egg or sperm cells while having no signs. This germline mosaicism makes the chance of another child with Costello syndrome low but not zero.
Hotspot positions: Most people with Costello syndrome have a change at the same hotspot in HRAS. Different hotspots can change how strongly the signal is turned on, which may shape features and severity.
Individual mosaicism: Sometimes the HRAS change happens after conception, so only some of the child’s cells carry it. This mosaic form can lead to milder or patchy features compared with a change present in all cells.
Family history: Having a parent with Costello syndrome gives a 50% chance for each pregnancy to inherit the HRAS change. If neither parent is affected, the chance of recurrence is usually much lower due to the de novo nature.
Genetic testing: DNA testing that reads the HRAS gene can confirm the diagnosis and pinpoint the exact change. Testing parents can check for mosaicism and help refine recurrence risk.
Lifestyle risk factors
Lifestyle habits do not cause Costello syndrome, but they can meaningfully shape symptoms, daily function, and complication risks. Understanding how lifestyle affects Costello syndrome helps families focus on changes that support growth, mobility, breathing, heart safety, and comfort. Practical choices in nutrition, activity, sleep, and daily care can complement medical treatment throughout life.
Insufficient energy intake can worsen poor growth and low muscle tone. Dietitian-guided calorie densification and texture changes can support weight gain and feeding safety.
Large or late meals can aggravate GERD and increase aspiration risk. Smaller, upright-fed meals and avoiding trigger foods may reduce coughing, pain, and night wakening.
Too little protein can hinder muscle strength and wound healing. Including protein at each meal supports motor therapy gains and surgical recovery.
Low calcium and vitamin D can worsen low bone density from hypotonia and limited activity. Routine supplementation guided by clinicians supports bone health and reduces fracture risk.
Risk prevention
Costello syndrome can’t be fully prevented because it’s a genetic condition present from birth. Prevention instead focuses on lowering the chance of complications and catching problems early so they’re easier to treat. Prevention is about lowering risk, not eliminating it completely. Knowing early symptoms of Costello syndrome complications helps families seek care sooner.
Meet with a genetics team to understand how Costello syndrome happens and the small chance of it occurring again. They can discuss options for future pregnancies and available testing.
Regular heart checks (ECG and echocardiogram) help find rhythm problems or thickening of the heart muscle early. Treating issues promptly lowers the risk of sudden events in people with Costello syndrome.
Scheduled abdominal ultrasounds and urine checks can help spot certain childhood cancers earlier in Costello syndrome. Earlier detection often means more treatment choices and better outcomes.
Early feeding therapy and reflux care support growth and reduce aspiration risk in Costello syndrome. Nutrition plans tailored by a dietitian can improve energy and development.
Transmission
Costello syndrome isn’t contagious; it’s a genetic condition caused by a change in a gene called HRAS. In most children with Costello syndrome, this change happens for the first time in the child and isn’t found in either parent.
The condition can be passed on in a dominant way—if a parent has Costello syndrome or the HRAS change, each pregnancy has a 50% chance of inheriting it. Even when parents test negative on a blood test, there’s a small chance of recurrence because the gene change can be present only in eggs or sperm (germline mosaicism). A genetics professional can explain how Costello syndrome is inherited and discuss the genetic transmission of Costello syndrome in your family.
When to test your genes
Consider genetic testing if a child shows features suggestive of Costello syndrome—slow growth, feeding difficulties, distinctive facial traits, loose skin, or heart issues—or if a close relative is diagnosed. Testing confirms the diagnosis, guides care (cardiac, feeding, developmental), and informs tumor surveillance. Prenatal testing may be discussed when ultrasound findings raise concern.
Diagnosis
For many families, the path to answers starts with noticing a pattern of feeding difficulties, slower growth, and distinctive facial features in a baby or young child. Doctors recognize these features and then use targeted tests to confirm the cause. Getting a diagnosis is often a turning point toward answers and support. In Costello syndrome, confirmation usually involves a genetic test for changes in the HRAS gene, and sometimes clues are seen even before birth on ultrasound.
Doctors look for a recognizable combination of features such as loose or soft skin, distinctive facial appearance, feeding challenges, and developmental delays. Patterns across growth, skin, heart, and movement help point toward Costello syndrome. A detailed family and health history can help narrow possibilities.
A blood or saliva test checks the HRAS gene for a disease-causing change. Finding a HRAS variant that fits the clinical picture confirms the genetic diagnosis of Costello syndrome.
If the features overlap with other related conditions, a multi-gene panel can test HRAS alongside similar genes. This approach can speed answers and reduce the need for multiple separate tests.
Before birth, ultrasound may show extra fluid around the baby (polyhydramnios), increased nuchal thickness, large size of certain body parts, or heart changes. These findings are not specific on their own but can prompt closer follow-up for possible Costello syndrome.
Stages of Costello syndrome
Costello syndrome does not have defined progression stages. It is a genetic condition present from birth, and features can shift with age rather than moving through set phases, so care focuses on regular checkups and tailored supports. Diagnosis usually combines a clinical exam and family history with a genetic test looking for a change in the HRAS gene; Genetic testing may be offered to clarify certain risks. Doctors also watch for early symptoms of Costello syndrome and longer-term health needs through ongoing assessments such as heart evaluations, feeding and growth monitoring, developmental checks, and age-appropriate cancer screening.
Outlook and prognosis
Many people ask, “What does this mean for my future?”, especially right after a diagnosis of Costello syndrome. The outlook is not the same for everyone, but most children with Costello syndrome grow into adulthood with careful, ongoing care. Growth and motor skills often improve over time, and communication usually becomes clearer, though learning and developmental support are commonly needed through school years and beyond. Heart health and feeding are big priorities early on; early symptoms of Costello syndrome like poor weight gain, low muscle tone, and heart rhythm issues can get better with treatment, but they do call for regular checkups.
Understanding the prognosis can guide planning and help you focus on what matters day to day. Life expectancy has improved compared with older reports, mainly because heart monitoring, nutrition support, and anesthesia planning are better now. Serious heart problems (such as cardiomyopathy or rhythm disturbances), breathing issues, and a higher-than-average risk of certain tumors account for most medical emergencies and, in rare cases, early death. Cancer risk is elevated in childhood, so scheduled screening for tumors of the muscle and bladder is standard; many people never develop cancer, and those who do often benefit from early detection.
Everyone’s journey looks a little different. With ongoing care, many people maintain good quality of life, take part in school or work with accommodations, and build strong social ties. Looking at the long-term picture can be helpful: plan for regular heart reviews, tumor screening in childhood, eye and orthopedic care as needed, and transition planning for adult services. Talk with your doctor about what your personal outlook might look like, including how your child’s specific health findings and the known gene change relate to long-term risks and supports.
Long-term effects
Costello syndrome is a lifelong genetic condition with features that change from infancy into adulthood. Early features of Costello syndrome often include feeding difficulties and slow growth, while later years may bring joint stiffness or skin changes. Everyone’s path looks different, and ongoing support can make a meaningful difference over time. The long-term outlook varies with heart involvement and tumor risk, and many people now live into adulthood.
Short height is common, with growth that trails peers across childhood. Heads can look relatively large compared with body size.
Motor and speech skills often arrive later than expected. Many have mild to moderate learning disability, with social strengths that can stand out.
Thickened heart muscle and rhythm problems occur more often in Costello syndrome. These heart features can stay stable or change over time.
The lifetime risk of specific tumors is higher than average in Costello syndrome. Childhood cancers such as rhabdomyosarcoma or neuroblastoma are more likely, and bladder cancer can appear in adolescence or young adulthood.
How is it to live with Costello syndrome?
Daily life with Costello syndrome often means juggling frequent medical visits, therapies, and school supports while celebrating steady, hard-won gains in movement, speech, and learning. Many children and adults benefit from structured routines, extra time for tasks, and adaptive tools; fatigue, feeding challenges, and orthopedic or heart monitoring needs can shape the pace of the day. Families, siblings, and caregivers commonly become skilled advocates, coordinating care across specialists and leaning on community networks, which can be both demanding and deeply connecting. With early interventions, consistent follow-up, and a team that listens, many living with Costello syndrome build meaningful friendships, find their strengths, and participate fully in family and community life.
Treatment and drugs
Treatment for Costello syndrome focuses on managing symptoms and preventing complications over time. Because it affects several body systems, care is usually coordinated by a team—typically including cardiology, endocrinology, neurology, orthopedics, dermatology, nutrition, speech and physical therapy, and genetics. Supportive care can make a real difference in how you feel day to day, from feeding support and growth hormone evaluation to therapies that build strength, improve movement, and support speech and learning. Heart monitoring and treatment of rhythm problems, regular checks for certain tumors, eye and hearing care, and management of joint tightness, reflux, and skin issues are common parts of a plan. Not every treatment works the same way for every person, so your doctor may adjust recommendations as needs change from infancy through adulthood.
Non-drug treatment
People with Costello syndrome often benefit from coordinated, non-drug care that grows with them from infancy into adulthood. Noticing early symptoms of Costello syndrome can help start therapies sooner and support feeding, movement, and communication. Non-drug treatments often lay the foundation for daily function while medical teams address heart, breathing, and tumor risks. Plans are tailored to age and abilities, and adjusted as needs change.
Targeted exercises build strength, balance, and endurance in weak or tight muscles. Stretching and play-based movement can reduce toe-walking and support safer mobility.
Skills for dressing, feeding, writing, and play are practiced step by step. Hand-strength and sensory strategies help with fine-motor control and daily independence.
Early work on sound production, expressive language, and understanding supports communication. Therapists also address oral-motor skills that affect chewing and swallowing.
Feeding therapy teaches safer swallowing and reduces choking risk. Strategies may include pacing, positioning, and texture changes for people with Costello syndrome.
Your genes may have an impact on how drugs work for you
Drugs used in Costello syndrome can act differently because rare HRAS gene changes alter how cells grow and signal, which can shift a medication’s benefits and side effects. Pharmacogenetic testing and careful dosing help clinicians choose safer, more effective options.
Pharmacological treatments
Medicines for Costello syndrome focus on easing symptoms and protecting the heart, stomach, and overall comfort. They’re tailored to each person’s needs and change as children grow. Medicines can also help with early symptoms of Costello syndrome such as reflux or fast heart rhythms. Not everyone responds to the same medication in the same way.
Drugs like propranolol, atenolol, or nadolol can slow fast heart rhythms and help control palpitations. In Costello syndrome, they are often a first step for supraventricular tachycardia.
Enalapril or captopril can lower the heart’s workload and support heart function if the heart muscle is thickened. Regular blood pressure and kidney checks are needed.
Sotalol, flecainide, or amiodarone may be used by cardiology teams when rhythm problems persist despite other steps. These drugs need close ECG and blood monitoring.
Furosemide or spironolactone can reduce fluid buildup if heart failure symptoms appear. This can ease breathing and swelling in children with Costello syndrome.
Genetic influences
In Costello syndrome, a single gene called HRAS carries a change that pushes cell-growth signals too high. This change almost always arises for the first time in the child and isn’t inherited from either parent. If a parent does carry the HRAS change, one changed copy is enough to pass it on, so each pregnancy has a 50% chance of inheriting it. Even with the same gene change, people can have different symptoms and different levels of medical needs. Rarely, a parent may have the change in only some of their cells (mosaicism), which can make recurrence possible even when the parent looks unaffected. Genetic testing that looks for HRAS changes can confirm Costello syndrome, guide care, and support family planning. Knowing the genetic cause can also help explain early symptoms of Costello syndrome and what to monitor over time.
Is Costello syndrome genetic?
Genetics is central in Costello syndrome. Nearly all cases result from new (de novo) changes in the HRAS gene, which acts like a growth “dimmer switch” stuck too high. Inherited cases are rare, so recurrence risk is usually low but not zero.
Pharmacogenetics—how genetics influence drug effects
Costello syndrome stems from changes in a gene called HRAS, but this usually doesn’t determine the exact dose of day-to-day medicines. Care is tailored to the features you live with—such as heart rhythm issues, reflux, feeding challenges, and tight muscles—and doctors choose medicines based on those needs. Genetic testing can sometimes identify how your body handles certain drugs, such as some pain relievers or antidepressants, which can help fine-tune dosing when needed. If cancer screening finds a tumor—a known risk in Costello syndrome—oncology teams may use separate drug–gene checks to reduce side effects and guide chemotherapy choices. Targeted medicines aimed at the same cell pathway affected by HRAS are being studied, but they’re not yet standard drug treatment for Costello syndrome. For anesthesia and procedures, planning is driven more by airway, heart, and muscle considerations than by HRAS itself, so sharing any past drug reactions helps the team choose safer options.
Interactions with other conditions
Living with Costello syndrome often means other health issues can have a bigger impact than usual. During a bad cold or the flu, weak muscle tone, sleep apnea, and heart rhythm problems can flare together—A condition may “exacerbate” (make worse) symptoms of another. Costello syndrome also overlaps with related conditions in the same pathway, such as Noonan syndrome or cardio‑facio‑cutaneous syndrome, so early symptoms of Costello syndrome can look similar and lead to mixed evaluations or shared management plans. There is an increased risk of certain tumors, and if cancer treatment is needed, doctors may adjust chemotherapy or anesthesia because of heart changes (like thickened heart muscle) and airway concerns. Ongoing reflux and feeding difficulties can raise the chance of chest infections, and repeated infections can in turn strain breathing and the heart. Coordinated care across cardiology, oncology, respiratory, and nutrition helps ensure one condition’s treatment does not unintentionally worsen another.
How genes can cause diseases
Humans have more than 20,000 genes, each carrying out one or a few specific functions in the body. One gene instructs the body to digest lactose from milk, another tells the body how to build strong bones and another prevents the body's cells from beginning to multiply uncontrollably and developing into cancer. As all of these genes combined are the building instructions for our body, a defect in one of these genes can have severe health consequences.
Through decades of genetic research, we know the genetic code of any healthy/functional human gene. We have also identified that in certain positions on a gene, some individuals may have a different genetic letter from the one you have. We call these hotspots "Genetic Variations" or "Variants" in short. In many cases, studies have been able to show that having the genetic letter "G" in the position makes you healthy, but having the letter "A" in the same position disrupts the gene function and causes a disease. Genopedia allows you to view these variants in genes and summarizes all that we know from scientific research, which genetic letters (Genotype) have good or bad consequences on your health or on your traits.
History
Throughout history, people have described children who were small at birth, grew slowly, and later developed loose skin on the hands and feet, broad lips, and a friendly, socially outgoing style. Families and communities once noticed patterns of feeding struggles in infancy, delays in walking and talking, and, later on, joint tightness or heart concerns that puzzled doctors of the time. In some households, relatives remembered a child with a similar look and health needs, even if no name was given.
First described in the medical literature as a cluster of distinctive facial features, growth delays, and heart rhythm issues, the condition gradually took shape as a recognizable syndrome. Early reports focused on what could be seen and measured—short stature, flexible joints when young that sometimes stiffened with age, and thickened skin on the palms and soles. As medical science evolved, careful comparisons showed that this pattern was different from other rare growth and development syndromes.
In recent decades, knowledge has built on a long tradition of observation. The syndrome became known as Costello syndrome, and reports from clinics across the world helped map out its range: from early feeding problems and slow weight gain to risks like certain heart problems and, less commonly, specific childhood tumors. Not every early description was complete, yet together they built the foundation of today’s knowledge.
Advances in genetics added clarity, explaining why so many features travel together. Researchers connected Costello syndrome to changes in a pathway that guides cell growth and development, which helped distinguish it from look‑alike conditions in the same biological family. With this insight, doctors could confirm the diagnosis with genetic testing rather than relying only on appearance and early symptoms of Costello syndrome.
Over time, descriptions became more balanced, noting both the medical needs and the strengths that many people with Costello syndrome share, such as social warmth, determination, and progress with tailored therapies. This shift shaped care: early feeding support, regular heart checks, growth and hormone monitoring, and watchfulness for learning needs became part of standard plans.
Looking back helps explain why modern care is proactive. What once seemed like scattered findings—loose skin here, a heart rhythm issue there—now fits a clear pattern with practical steps to support health and development. Today, the history of Costello syndrome continues to evolve, as long‑term studies refine our understanding of life span, adult health, and the best ways to support people living with the condition at every age.