National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

LEOPARD syndrome


Other Names:
Lentigines, Electrocardiographic conduction abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth, Deafnes; Multiple lentigines syndrome; Cardiomyopathic lentiginosis; Lentigines, Electrocardiographic conduction abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth, Deafnes; Multiple lentigines syndrome; Cardiomyopathic lentiginosis; Noonan syndrome with multiple lentigines See More
Categories:
LEOPARD syndrome is an inherited condition characterized by abnormalities of the skin, heart, inner ears, and genitalia. The acronym LEOPARD describes the features of the syndrome:
(L)entigines - dark spots on the skin
(E)lectrocardiographic conduction defects - abnormalities of the electrical activity of the heart
(O)cular hypertelorism - widely spaced eyes
(P)ulmonary stenosis - obstruction of the normal outflow of blood from the right ventricle of the heart
(A)bnormalities of the genitalia
(R)etarded (slowed) growth resulting in short stature
(D)eafness[1]

There are 3 types of LEOPARD syndrome, which are distinguished by their genetic cause. Type 1 is caused by mutations in the PTPN11 gene; type 2 is caused by mutations in the RAF1 gene; and type 3 is caused by mutations in the BRAF gene. Other cases are caused by mutations in the MAP2K1  gene, and in some cases the cause is unknown. LEOPARD syndrome is inherited in an autosomal dominant manner. It can be inherited from an affected parent, or it can be due to a new mutation in a person with no family history of the condition.[2]

Leopard 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.[3][4]
Last updated: 6/28/2016

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.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal pulmonary valve morphology 0001641
Abnormality of the pulmonary artery
Abnormality of lung artery
0004414
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat
[ more ] 		0011675
Bundle branch block 0011710
Freckling 0001480
Hyperextensible skin
Hyperelastic skin
Skin hyperelasticity
Stretchable skin
[ more ] 		0000974
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
0001639
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation
[ more ] 		0001511
Melanocytic nevus
Beauty mark
0000995
Pulmonic stenosis
Narrowing of pulmonic valve
0001642
Severe sensorineural hearing impairment 0008625
30%-79% of people have these symptoms
Atrioventricular canal defect 0006695
Cryptorchidism
Undescended testes
Undescended testis
[ more ] 		0000028
Decreased fertility
Abnormal fertility
0000144
Low-set, posteriorly rotated ears 0000368
Mitral valve prolapse 0001634
Pectus carinatum
Pigeon chest
0000768
Pectus excavatum
Funnel chest
0000767
Ptosis
Drooping upper eyelid
0000508
Scapular winging
Winged shoulder blade
0003691
Sprengel anomaly
High shoulder blade
0000912
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge
[ more ] 		0000431
5%-29% of people have these symptoms
Abnormal endocardium morphology 0004306
Abnormal localization of kidney
Abnormal localisation of kidneys
0100542
Abnormality of the voice
Voice abnormality
0001608
Aplasia/Hypoplasia of the abdominal wall musculature
Absent/small abdominal wall muscles
Absent/underdeveloped abdominal wall muscles
[ more ] 		0010318
Brachycephaly
Short and broad skull
0000248
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment
[ more ] 		0100543
Curly hair 0002212
Dilatation
Wider than typical opening or gap
0002617
Excessive wrinkled skin 0007392
Global developmental delay 0001263
Hypospadias 0000047
Intellectual disability, mild
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation
[ more ] 		0001256
Melanoma 0002861
Myelodysplasia 0002863
Myocardial infarction
Heart attack
0001658
Neuroblastoma
Cancer of early nerve cells
0003006
Scoliosis 0002650
Spina bifida occulta 0003298
Subcutaneous nodule
Firm lump under the skin
Growth of abnormal tissue under the skin
[ more ] 		0001482
Triangular face
Face with broad temples and narrow chin
Triangular facial shape
[ more ] 		0000325
Percent of people who have these symptoms is not available through HPO
Abnormal aortic valve morphology 0001646
Abnormal mitral valve morphology 0001633
Abnormality of the sternum
Sternal anomalies
0000766
Aplasia of the ovary
Absent ovary
0010463
Autosomal dominant inheritance 0000006
Cafe-au-lait spot 0000957
Cleft palate
Cleft roof of mouth
0000175
Cubitus valgus
Outward turned elbows
0002967
Delayed menarche
Delayed start of first period
0012569
Delayed puberty
Delayed pubertal development
Delayed pubertal growth
Pubertal delay
[ more ] 		0000823
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
Depressed nasal ridge
Flat nose
Recessed nasal ridge
[ more ] 		0000457
Dolichocephaly
Long, narrow head
Tall and narrow skull
[ more ] 		0000268
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Dry skin 0000958
Epicanthus
Eye folds
Prominent eye folds
[ more ] 		0000286
Hyperkeratosis 0000962
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ] 		0000316
Hypoplasia of the ovary
Underdeveloped ovary
0008724
Hyposmia 0004409
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Kyphoscoliosis 0002751
Limited elbow movement
Decreased elbow mobility
Limited elbow mobility
Restricted elbow motion
[ more ] 		0002996
Low-set ears
Low set ears
Lowset ears
[ more ] 		0000369
Mandibular prognathia
Big lower jaw
Increased projection of lower jaw
Increased size of lower jaw
Large lower jaw
Prominent chin
Prominent lower jaw
[ more ] 		0000303
Micropenis
Short penis
Small penis
[ more ] 		0000054
Missing ribs
Absent ribs
Decreased rib number
[ more ] 		0000921
Multiple cafe-au-lait spots 0007565
Multiple lentigines 0001003
Neonatal hypotonia
Low muscle tone, in neonatal onset
0001319
Numerous nevi
Numerous moles
0001054
Parietal bossing 0000242
Posteriorly rotated ears
Ears rotated toward back of head
0000358
Protruding ear
Prominent ear
Prominent ears
[ more ] 		0000411
Seizure 0001250
Sensorineural hearing impairment 0000407
Shield chest 0000914
Short neck
Decreased length of neck
0000470
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Strabismus
Cross-eyed
Squint
Squint eyes
[ more ] 		0000486
Subvalvular aortic stenosis
Narrowing of blood vessel below aortic heart valve
0001682
Tetralogy of Fallot 0001636
Thick lower lip vermilion
Increased volume of lower lip
Plump lower lip
Prominent lower lip
[ more ] 		0000179
Third degree atrioventricular block
Complete heart block
0001709
Unilateral renal agenesis
Absent kidney on one side
Missing one kidney
Single kidney
[ more ] 		0000122
Webbed neck
Neck webbing
0000465
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Last updated: 7/1/2020

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

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

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 

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

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 LEOPARD syndrome. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • 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. 
    LEOPARD syndrome 1
    LEOPARD syndrome 2
    LEOPARD syndrome 3
  • 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 LEOPARD syndrome. Click on the link to view a sample search on this topic.

News

Other Conferences

  • Neurofibromatoses and RASopathies: Their Management, Diagnosis, Current and Future Therapeutic Avenues
    Monday, September 30, 2013 - Tuesday, October 01, 2013
    Location: Radisson Blu Hotel, Cardiff, Wales
    Description: This international meeting will provide a most comprehensive and up to date account of recent developments in this field. Internationally recognized experts from the UK, Europe and the USA will speak on neurofibromatoses and rasopathies. This meeting will be suitable for medical geneticists, oncologists, dermatologists, neurologists, endocrinologists, psychiatrists, molecular and cellular biologists, genetic counsellors and general practitioners.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • My grandson has been diagnosed with LEOPARD syndrome. We have just noticed that his eyes are beginning to cross. Is this a sign also? See answer


  1. LEOPARD syndrome. National Organization for Rare Disorders Web site. 2012; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/718/viewAbstract.
  2. Gelb BD & Tartaglia M. LEOPARD syndrome. GeneReviews. 2015; http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=leopard.
  3. The “Classic” RASopathy Syndromes. RASopathiesNet. https://rasopathiesnet.org/rasopathies/syndromes/.
  4. Rauen KA. The RASopathies. Annu Rev Genomics Hum Genet. 2013; 14:355-369. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115674/.