Costello Syndrome: Causes, Symptoms, Diagnosis and Care

Costello syndrome is a very rare genetic condition that affects many parts of a child’s body, including the heart, muscles, bones, skin, brain, and growth. Although there is no cure, early diagnosis and regular medical care can greatly improve comfort, safety, and quality of life.

What Is Costello Syndrome?

Costello syndrome is a genetic disorder caused by a change in a gene called HRAS. This change happens very early in development, before a baby is born. The altered gene sends extra “grow and divide” signals to cells, which affects how tissues and organs form and function.

Doctors classify Costello syndrome as a type of RASopathy. RASopathies are conditions caused by changes in genes that control the RAS/MAPK pathway, a key signaling system for cell growth and development.

How rare is it?

• Costello syndrome is extremely rare, with only a few hundred individuals reported worldwide.
• It affects all sexes and ethnic backgrounds.
• Because it is so uncommon, many families reach diagnosis only after seeing several specialists.

Genetic Cause and Inheritance

The HRAS gene provides instructions for making the HRAS protein, which helps control how quickly cells grow and divide. In Costello syndrome, a gain-of-function mutation makes this protein overactive, so cells receive stronger or constant growth signals.

Key points about the HRAS gene

• Most children with Costello syndrome have a change in just one copy of the HRAS gene.
• The condition is considered autosomal dominant: a single changed copy is enough to cause symptoms.
• In the vast majority of cases, the mutation is new (de novo) and not inherited from either parent.
• Parents usually have typical genes and are not affected.

Once identified in a child, the HRAS mutation can, however, be passed on to future offspring if that child later becomes a parent.

How Costello Syndrome Affects the Body

Costello syndrome involves multiple organ systems. Not every child will have every feature, and the severity can vary widely, even within the same family.

Common medical features

• Feeding and growth difficulties in infancy
• Short stature and delayed growth after birth
• Distinctive facial features
• Loose, soft skin with deep creases, especially on hands and feet
• Joint laxity and skeletal differences
• Heart problems, including rhythm issues and thickened heart muscle
• Developmental delay and intellectual disability
• Increased risk of tumors (cancerous and noncancerous)

Signs and Symptoms by Age

Some signs of Costello syndrome may show up during pregnancy, while others become clearer in infancy, childhood, or adolescence.

Physical and Medical Features in More Detail

Growth and nutrition

• Many infants struggle with feeding and may not gain weight as expected without medical support.
• Growth delay after birth commonly leads to short adult height.
• Some children have lower levels of growth hormone, and hormone treatment may be considered on a case-by-case basis.

Heart and circulation

• Common heart findings include:
  • Hypertrophic cardiomyopathy (thickened heart muscle)
  • Pulmonary valve stenosis (narrowed valve from heart to lungs)
  • Abnormal heart rhythms, especially atrial tachycardia
• Regular cardiology visits and heart imaging (such as echocardiograms) are essential.

Skin, hair, and joints

• Loose, soft skin with deep creases on palms and soles is typical.
• Dry, thickened patches of skin (hyperkeratosis) can occur on hands and feet.
• Hair may be curly, sparse, or fine.
• Joints are often very flexible (joint laxity), which can later shift toward stiffness, especially in the ankles.

Brain, nerves, and learning

• Most children have mild to moderate intellectual disability.
• Motor delays are common due to low muscle tone and joint laxity.
• Some children may develop seizures, hydrocephalus, or structural brain differences.
• Despite challenges, many have a very social, engaging temperament.

Cancer and tumor risk

• Children with Costello syndrome have a higher risk of several tumors, including:
  • Embryonal rhabdomyosarcoma (soft tissue cancer)
  • Neuroblastoma (nerve tissue cancer)
  • Transitional cell carcinoma of the bladder in adolescence or adulthood
• Overall lifetime cancer risk is estimated around 10–15% in some expert reports.
• Noncancerous skin growths called papillomas are very common.

How Doctors Diagnose Costello Syndrome

Diagnosis is based on a combination of physical findings and confirmatory genetic testing.

Clinical evaluation

A pediatrician or genetic specialist may suspect Costello syndrome when they notice a pattern of features such as:

• Feeding problems and poor weight gain
• Short stature and developmental delays
• Characteristic facial appearance and loose skin
• Congenital heart disease or unusual heart rhythms
• Flexible joints and skeletal differences

Genetic testing

• Diagnosis is confirmed by a molecular test that looks for a pathogenic variant in the HRAS gene.
• Testing may be done from a blood sample or sometimes saliva.
• Once a mutation is identified in the child, parents may be offered testing to clarify recurrence risk in future pregnancies.

Other tests at diagnosis

• Echocardiogram and electrocardiogram (ECG) to assess heart structure and rhythm
• Growth and hormone evaluation
• Brain imaging if neurological symptoms are present
• Baseline screening for tumors, depending on age and guidelines

Treatment and Ongoing Care

There is currently no cure for Costello syndrome, but there are many treatments that address individual symptoms and medical concerns. Care is usually coordinated by a team of specialists.

Typical members of the care team

• Pediatrician or developmental pediatrician
• Medical geneticist and genetic counselor
• Cardiologist
• Gastroenterologist and nutrition specialist
• Neurologist and orthopedic specialist
• Dermatologist, oncologist, and physical, occupational, and speech therapists

Managing feeding and growth

• Thickened feeds, reflux medication, and positioning strategies for infants
• Temporary or long-term feeding tube (e.g., gastrostomy) if oral intake is not enough
• Close monitoring of weight and growth charts
• Assessment for and, rarely, treatment of growth hormone deficiency, when appropriate

Heart care

• Medication to control heart rhythm or blood flow issues
• Regular echocardiograms and ECGs for early detection of problems
• In some cases, procedures or surgery to address structural heart disease

Support for movement and learning

• Early intervention services for babies and toddlers
• Physical therapy to build strength, balance, and mobility
• Occupational therapy for fine motor skills and daily activities
• Speech and language therapy to support communication
• Individualized education plans (IEPs) in school to match learning needs

Cancer surveillance

Because of the increased tumor risk, many experts recommend a structured surveillance plan, which may include:

• Regular physical examinations and careful attention to new lumps, swelling, pain, or unexplained symptoms
• Periodic imaging or urine tests, according to current expert guidelines and the child’s age
• Prompt evaluation of concerning findings by oncology specialists

Day-to-Day Life With Costello Syndrome

Living with Costello syndrome can be medically complex, but many children develop strong personalities, close friendships, and active lives with the right supports.

At home

• Maintain a written list of your child’s diagnoses, medications, and specialists.
• Use clear, predictable routines to help with learning and behavior.
• Encourage movement within safe limits to support muscle strength and joint health.
• Watch for changes in energy, breathing, feeding, or new pain, and contact healthcare providers promptly.

At school

• Share medical and educational reports with school staff.
• Request an individualized plan that may include:
  • Extra time for tasks and tests
  • Speech, occupational, or physical therapy during school hours
  • Supports for mobility or fatigue
• Help classmates understand differences in a respectful, age-appropriate way, if your child is comfortable.

Emotional and family support

• Connecting with other families affected by Costello syndrome or RASopathies can reduce isolation and provide practical tips.
• Genetic counseling can help families understand recurrence risks and family planning options.
• Psychological support may be useful for parents, siblings, and the child as they navigate medical procedures and educational challenges.

Outlook and Long-Term Considerations

People with Costello syndrome are living longer due to improved diagnosis, heart care, and cancer surveillance. The condition is lifelong, and some health issues may emerge or change with age, so regular follow-up remains important throughout adolescence and adulthood.

Long-term priorities

• Ongoing cardiac monitoring
• Continued cancer screening according to expert recommendations
• Orthopedic follow-up for spine and joint health
• Transition planning from pediatric to adult care
• Vocational and independent living supports, tailored to the individual’s abilities

Frequently Asked Questions (FAQs)