Rare Hematology News

Disease Profile

Neurofibromatosis-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.

Unknown

Age of onset

Infancy

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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)

NFNS; Noonan neurofibromatosis syndrome; Neurofibromatosis with Noonan phenotype

Categories

Congenital and Genetic Diseases; Heart Diseases; Rare Cancers;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 638

Definition
Neurofibromatosis-Noonan syndrome (NFNS) is a RASopathy and a variant of neurofibromatosis type 1 (NF1) characterized by the combination of features of NF1, such as café-au-lait spots, iris Lisch nodules, axillary and inguinal freckling, optic nerve glioma and multiple neurofibromas, and Noonan syndrome (NS), such as short stature, typical facial features (hypertelorism, ptosis, downslanting palpebral fissures, low-set posteriorly rotated ears with a thickened helix, and a broad forehead), congenital heart defects and unusual pectus deformity. As these three entities have significant phenotypic overlap, molecular genetic testing is often necessary for a correct diagnosis (such as when café-au-lait spots are present in patients diagnosed with NS).

Visit the Orphanet disease page for more resources.

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
Abdominal wall muscle weakness
0009023
Abnormality of the helix
0011039
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
0001639
Low-set, posteriorly rotated ears
0000368
Multiple cafe-au-lait spots
0007565
Ptosis
Drooping upper eyelid
0000508
Pulmonic stenosis
Narrowing of pulmonic valve
0001642
Short stature
Small stature
Decreased body height

[ more ]

0004322
Specific learning disability
0001328
Webbed neck
Neck webbing
0000465
30%-79% of people have these symptoms
Abnormal thorax morphology
Abnormality of the chest
0000765
Abnormality of the lymphatic system
0100763
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Prolonged bleeding time
0003010
1%-4% of people have these symptoms
Axillary freckling
0000997
Cubitus valgus
Outward turned elbows
0002967
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Lisch nodules
0009737
Low posterior hairline
Low hairline at back of neck
0002162
Low-set ears
Low set ears
Lowset ears

[ more ]

0000369
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Malar flattening
Zygomatic flattening
0000272
Neuroblastoma
Cancer of early nerve cells
0003006
Optic nerve glioma
0009734
Pectus excavatum
Funnel chest
0000767
Plexiform neurofibroma
0009732
Posteriorly rotated ears
Ears rotated toward back of head
0000358
Scoliosis
0002650
Thick vermilion border
Full lips
Increased volume of lip
Plump lips
Prominent lips
Thick lips

[ more ]

0012471
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay

[ more ]

0000750
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
Global developmental delay
0001263
Inguinal freckling
Freckles in groin region
0030052
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface

[ more ]

0011800
Muscle weakness
Muscular weakness
0001324
Pectus excavatum of inferior sternum
0000915
Prominent nasolabial fold
Deep laugh lines
Deep smile lines
Prominent laugh lines
Prominent smile lines

[ more ]

0005272
Secundum atrial septal defect
0001684
Short neck
Decreased length of neck
0000470
Superior pectus carinatum
0000917

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.

      In-Depth Information

      • 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 Neurofibromatosis-Noonan syndrome. Click on the link to view a sample search on this topic.