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Disease Profile

Noonan 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.
1-5 / 10 000

33,100 - 165,500

US Estimated

1-5 / 10 000

51,350 - 256,750

Europe Estimated

Age of onset

Childhood

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ICD-10

Q87.1

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)

Male Turner Syndrome; Noonan-Ehmke syndrome; Ullrich-Noonan syndrome;

Categories

Blood Diseases; Congenital and Genetic Diseases; Endocrine Diseases;

Summary

Noonan syndrome is a genetic disorder that causes abnormal development of multiple parts of the body. Features of Noonan syndrome may include a distinctive facial appearance, short stature, a broad or webbed neck, congenital heart defects, bleeding problems, problems with bone structure (skeletal malformations), and developmental delay.[1][2] Noonan syndrome may be caused by a mutation in any of several genes, and can be classified into subtypes based on the responsible gene. It is typically inherited in an autosomal dominant manner, but many cases are due to a new mutation and are not inherited from either parent. Treatment depends on the symptoms present in each person.[3]

Noonan 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. Other conditions in this group include:[4]

Symptoms

Some of the signs and symptoms seen in people with Noonan syndrome (NS) are listed below.[1][3] Please note that the list below does not include all possible symptoms of NS and that not all people with NS will have all of these the signs and symptoms. In general, the signs and symptoms of NS are more obvious early in life and become less obvious as individuals get older.[3]

  • Head/Neck:
    • Widely spaced eyes (hypertelorism)
    • Large ears rotated back
    • Short webbed neck
    • Droopy eyelids (ptosis)
    • Low hairline
    • Multiple giant cell lesions (MGCL): painless, benign growths in the jaw that can lead to dental or orthodontic issues
  • Heart:
    • Pulmonary stenosis
    • Aortic regurgitation
    • Atrial septal defect
  • Skeletal:
    • Short stature
    • Concave chest (pectus excavatum)
    • Bending or curvature of the finger (clinodactyly)
    • Weak bones (generalized osteopenia)
  • Skin:
  • Neurological:
    • Delayed milestones due to low muscle tone
    • Developmental delay
    • Learning disabilities or intellectual impairment
  • Bleeding disorder
  • Undescended testicles (cryptorchidism)

A syndrome named Noonan-like/multiple giant cell lesion syndrome used to be considered a separate condition from Noonan syndrome. It is now known that multiple giant cell lesions are one of the possible symptoms that can occur in people with Noonan syndrome.[5]

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
Aplasia/Hypoplasia of the abdominal wall musculature
Absent/small abdominal wall muscles
Absent/underdeveloped abdominal wall muscles

[ more ]

0010318
Cystic hygroma
0000476
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Dysarthria
Difficulty articulating speech
0001260
Enlarged thorax
Wide rib cage
0100625
High forehead
0000348
High palate
Elevated palate
Increased palatal height

[ more ]

0000218
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Hypogonadotropic hypogonadism
0000044
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Low-set, posteriorly rotated ears
0000368
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface

[ more ]

0011800
Muscle weakness
Muscular weakness
0001324
Pectus carinatum
Pigeon chest
0000768
Pectus excavatum
Funnel chest
0000767
Proptosis
Bulging eye
Eyeballs bulging out
Prominent eyes
Prominent globes
Protruding eyes

[ more ]

0000520
Ptosis
Drooping upper eyelid
0000508
Pulmonary artery stenosis
Narrowing of lung artery
0004415
Short stature
Small stature
Decreased body height

[ more ]

0004322
Thick lower lip vermilion
Increased volume of lower lip
Plump lower lip
Prominent lower lip

[ more ]

0000179
Thickened helices
0000391
Thickened nuchal skin fold
Thickened skin folds of neck
Thickened skin over the neck

[ more ]

0000474
Triangular face
Face with broad temples and narrow chin
Triangular facial shape

[ more ]

0000325
Webbed neck
Neck webbing
0000465
Wide intermamillary distance
Wide-spaced nipples
Widely spaced nipples
Widely-spaced nipples

[ more ]

0006610
30%-79% of people have these symptoms
Abnormal bleeding
Bleeding tendency
0001892
Abnormal dermatoglyphics
Abnormal fingerprints
0007477
Abnormal hair quantity
0011362
Abnormal platelet function
0011869
Abnormal pulmonary valve morphology
0001641
Abnormality of coagulation
0001928
Abnormality of the spleen
0001743
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat

[ more ]

0011675
Coarse hair
Coarse hair texture
0002208
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

0002750
Feeding difficulties in infancy
0008872
Hepatomegaly
Enlarged liver
0002240
Low posterior hairline
Low hairline at back of neck
0002162
Muscular hypotonia
Low or weak muscle tone
0001252
Scoliosis
0002650
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
5%-29% of people have these symptoms
Aplasia of the semicircular canal
0011381
Brachydactyly
Short fingers or toes
0001156
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Hypogonadism
Decreased activity of gonads
0000135
Lymphedema
Swelling caused by excess lymph fluid under skin
0001004
Melanocytic nevus
Beauty mark
0000995
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Radioulnar synostosis
Fused forearm bones
0002974
Sensorineural hearing impairment
0000407
1%-4% of people have these symptoms
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
Bruising susceptibility
Bruise easily

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.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Treatment

    Management of Noonan syndrome generally focuses on the specific signs and symptoms present in each person. Treatments for the complications of Noonan syndrome (such as cardiovascular problems) are generally standard and do not differ from treatment in the general population.[3]

    Developmental disabilities are addressed by early intervention programs. Some children with Noonan syndrome may need special help in school, including for example, an individualized educational program (IEP).[3] 

    Treatment for bleeding problems depends on the cause.[3] Growth hormone (GH) therapy can increase the rate at which a child with Noonan syndrome grows in most cases. GH therapy during childhood and teen years may also increase final adult height slightly, often enough to reach the low normal range of average height.[3][6]

    Management Guidelines

    • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

      FDA-Approved Treatments

      The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

      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

        • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
        • MedlinePlus Genetics contains information on Noonan syndrome. This website is maintained by the National Library of Medicine.
        • The Merck Manual provides information on this condition for patients and caregivers.
        • The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.
        • 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.
          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • 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. 
          • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for Noonan syndrome in a table called Phenotypic Series. Each entry in OMIM includes 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 Noonan syndrome. Click on the link to view a sample search on this topic.

            References

            1. Noonan syndrome. Genetics Home Reference. May, 2016; https://ghr.nlm.nih.gov/condition/noonan-syndrome.
            2. Learning About Noonan Syndrome. National Human Genome Research Institute. 2013; https://www.genome.gov/25521674.
            3. Judith E Allanson and Amy E Roberts. Noonan Syndrome. GeneReviews. February 25, 2016; https://www.ncbi.nlm.nih.gov/books/NBK1124/.
            4. Rauen KA. The RASopathies. Annu Rev Genomics Hum Genet. 2013; 14:355-369. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115674/.
            5. Karbach J, Coerdt W, Wagner W, Bartsch O. Case report: Noonan syndrome with multiple giant cell lesions and review of the literature. Am J Med Genet A. 2012 Sept; 158A(9):2283-9. https://www.ncbi.nlm.nih.gov/pubmed/22848035.
            6. Dahlgren J. GH therapy in Noonan syndrome: Review of final height data. Horm Res. December, 2009; 72 (Suppl 2):46-48. https://www.ncbi.nlm.nih.gov/pubmed/20029237.
            7. Binder G. et al. Health and quality of life in adults with Noonan syndrome. J. Pediatr. September 2012; 161(3):501-505.
            8. Ineke van der Burgt. Noonan Syndrome. Orphanet Journal of Rare Diseases. 2007; 2:4:https://www.ojrd.com/content/2/1/4. Accessed 10/1/2013.
            9. Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. Lancet. January 26, 2013; 381(9863):333-342.

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