Rare Gastroenterology News

Disease Profile

Costello syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Neonatal

ICD-10

Q87.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Faciocutaneoskeletal syndrome; FCS syndrome

Categories

Congenital and Genetic Diseases; Heart Diseases; Nervous System Diseases;

Summary

Costello syndrome is a rare condition that affects many different parts of the body. Signs and symptoms generally include developmental delay, intellectual disability, distinctive facial features, loose folds of extra skin (especially on the hands and feet), and unusually flexible joints. Affected people may also have heart abnormalities such as tachycardia, structural heart defects, and hypertrophic cardiomyopathy. Beginning in early childhood, people with Costello syndrome additionally have an increased risk to develop certain cancerous and noncancerous tumors. Costello syndrome is caused by changes (mutations) in the HRAS gene. It is considered an autosomal dominant condition, but almost all cases are the result of de novo gene mutations and occur in people with no family history of the condition.[1][2][3] Treatment is based on the signs and symptoms present in each person.[3]

Costello syndrome belongs to a group of related conditions called the RASopathies. These conditions have some overlapping features and are all caused by genetic changes that disrupt the body's RAS pathway, affecting growth and development. The features of Costello syndrome overlap significantly with two of the RASopathies, cardiofaciocutaneous (CFC) syndrome and Noonan syndrome.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal fingernail morphology
Abnormal fingernails
Abnormality of the fingernails

[ more ]

0001231
Acanthosis nigricans
Darkened and thickened skin
0000956
Concave nail
Spoon-shaped nails
0001598
Deep-set nails
0001814
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

0002750
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Failure to thrive in infancy
Faltering weight in infancy
Weight faltering in infancy

[ more ]

0001531
Hyperkeratosis
0000962
Lack of skin elasticity
0100679
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Narrow palate
Narrow roof of mouth
0000189
Pulmonic stenosis
Narrowing of pulmonic valve
0001642
Redundant skin
Loose redundant skin
Redundant skin folds
Sagging, redundant skin

[ more ]

0001582
Short neck
Decreased length of neck
0000470
Short stature
Decreased body height
Small stature

[ more ]

0004322
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
Woolly hair
Kinked hair
0002224
30%-79% of people have these symptoms
Abnormal dermatoglyphics
Abnormal fingerprints
0007477
Abnormality of dental enamel
Abnormal tooth enamel
Enamel abnormalities
Enamel abnormality

[ more ]

0000682
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
Full cheeks
Apple cheeks
Big cheeks
Increased size of cheeks
Large cheeks

[ more ]

0000293
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn

[ more ]

0002020
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
0001639
Hypoplastic toenails
Underdeveloped toenails
0001800
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Keratoconus
Bulging cornea
0000563
Macroglossia
Abnormally large tongue
Increased size of tongue
Large tongue

[ more ]

0000158
Mitral valve prolapse
0001634
Papilloma
0012740
Polyhydramnios
High levels of amniotic fluid
0001561
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Thick lower lip vermilion
Increased volume of lower lip
Plump lower lip
Prominent lower lip

[ more ]

0000179
Thickened Achilles tendon
0004690
Thickened nuchal skin fold
Thickened skin folds of neck
Thickened skin over the neck

[ more ]

0000474
Ulnar deviation of finger
Finger bends toward pinky
0009465
5%-29% of people have these symptoms
Coarse facial features
Coarse facial appearance
0000280
Generalized hyperpigmentation
0007440
Large earlobe
Fleshy earlobe
Fleshy earlobes
Prominent ear lobes
prominent ear lobules

[ more ]

0009748
Large face
Big face
0100729
Low-set, posteriorly rotated ears
0000368
Poor suck
Poor sucking
0002033
Renal insufficiency
Renal failure
Renal failure in adulthood

[ more ]

0000083
Percent of people who have these symptoms is not available through HPO
Achilles tendon contracture
Shortening of the achilles tendon
Tight achilles tendon

[ more ]

0001771
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

0000463
Arnold-Chiari type I malformation
0007099
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat

[ more ]

0011675
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers

[ more ]

0001631
Autosomal dominant inheritance
0000006
Barrel-shaped chest
Barrel chest
0001552
Bladder carcinoma
0002862
Bronchomalacia
0002780
Cerebral atrophy
Degeneration of cerebrum
0002059
Curly hair

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • DermNet NZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated. DermNet NZ provides information about this condition.
      • Genetics Home Reference (GHR) contains information on Costello syndrome. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Costello syndrome. Click on the link to view a sample search on this topic.

          References

          1. Costello syndrome. Genetics Home Reference (GHR). July 2012; https://ghr.nlm.nih.gov/condition/costello-syndrome.
          2. Costello Syndrome. NORD. 2014; https://rarediseases.org/rare-diseases/costello-syndrome/.
          3. Gripp KW & Lin AE. Costello Syndrome. GeneReviews. January 2012; https://www.ncbi.nlm.nih.gov/books/NBK1507/.

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