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Disease Profile

LEOPARD 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

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)

Lentigines, Electrocardiographic conduction abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth, Deafnes; Multiple lentigines syndrome; Cardiomyopathic lentiginosis;

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Eye diseases;

Summary

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]

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 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
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
0001639
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Melanocytic nevus
Beauty mark
0000995
Multiple lentigines
0001003
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
Short stature
Decreased body height
Small stature

[ more ]

0004322
Sprengel anomaly
High shoulder blade
0000912
Webbed neck
Neck webbing
0000465
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
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
Vascular dilatation
Wider than typical opening or gap
0002617
1%-4% of people have these symptoms
Cubitus valgus
Outward turned elbows
0002967
Curly hair
0002212
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
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
Epidermal hyperkeratosis
Increased thickness of skin epidermis
0007543
Few cafe-au-lait spots
0007429
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
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
Narrow forehead
Decreased width of the forehead
0000341
Neonatal hypotonia
Low muscle tone, in neonatal onset

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.
    • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
    • Genetics Home Reference (GHR) contains information on LEOPARD 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.
      • 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.

        References

        1. LEOPARD syndrome. National Organization for Rare Disorders Web site. 2012; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/718/viewAbstract.
        2. Gelb BD & Tartaglia M. LEOPARD syndrome. GeneReviews. 2015; https://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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115674/.

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