How is LEOPARD syndrome 1 inherited?

LEOPARD syndrome 1 follows an autosomal dominant inheritance pattern. This means inheriting just one copy of the altered gene from either parent can cause the condition.

How is LEOPARD syndrome 1 diagnosed?

Information about diagnosis is currently limited for this condition.

Are there treatments for LEOPARD syndrome 1?

Information about treatment options and management approaches is currently limited for this condition.

What complications can arise from LEOPARD syndrome 1?

LEOPARD syndrome 1 can lead to heart-related issues, such as cardiomyopathy, which means the heart may not pump blood as well as it should. This can cause fatigue and other health problems. Since symptoms can vary, it's important to monitor any changes and work closely with healthcare providers.

How does LEOPARD syndrome 1 affect daily life?

Living with LEOPARD syndrome 1 may involve regular check-ups to monitor heart health and skin changes. The presence of lentigines, or dark spots on the skin, can also affect how someone feels about their appearance. Support from family and friends can help manage these daily challenges.

What is the life expectancy for someone with LEOPARD syndrome 1?

Information about life expectancy for individuals with LEOPARD syndrome 1 is currently limited. However, the presence of heart issues can impact overall health, so regular medical care is essential. Staying informed and proactive about health can help improve quality of life.

What specialists should be involved in the care of someone with LEOPARD syndrome 1?

Individuals with LEOPARD syndrome 1 may benefit from seeing a cardiologist to monitor heart health, as well as a dermatologist for skin concerns related to lentigines. A geneticist can also provide valuable information about the condition and its management. Coordinated care from these specialists can help address various aspects of the syndrome.

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LEOPARD syndrome 1 - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

LEOPARD syndrome 1

MONDO:0100082

Also known as:LEOPARD syndrome type 1LPRD1lentiginosis, cardiomyopathic

Overview

Any Noonan syndrome with multiple lentigines in which the cause of the disease is a heterozygous mutation in the PTPN11 gene on chromosome 12q24.

GeneticsAutosomal dominant · PTPN11 (chr 12)

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

Features include always present findings: Cafe-au-lait spot, Hypertelorism, Posteriorly rotated ears, and Multiple lentigines; and very common findings: Ptosis. 44 total HPO annotations.

Organ System	Phenotype Count	Example Features
Heart and blood vessels	5	Bundle branch block, Third degree atrioventricular block, Subvalvular aortic stenosis

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

PTPN11 function has not been fully characterized.

LEOPARD syndrome 1 is associated with mutations in the PTPN11 gene on chromosome 12.

GeneReviews

Clinical Guidance

No clinically relevant genotype-phenotype correlations for BRAF, MAP2K1, or RAF1 have been identified in individuals with NSML. PTPN11. In contrast to what is observed in Noonan syndrome, the NSML-associated pathogenic variants are strongly associated with a predisposition to hypertrophic cardiomyopathy . This specific correlation results from a differential impact of NS- and NSML-causing PTPN11 variants on intracellular signalling. In particular, different consequences have been documented on both the MAPK and PI3K-AKT-mTOR pathways .

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

Suggested clinical diagnostic criteria for Noonan syndrome with multiple lentigines (NSML) have been published .

Suggestive Findings

NSML should be suspected in individuals with one or more of the following cardinal features:

Lentigines
Cardiac abnormalities, particularly hypertrophic cardiomyopathy

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for LEOPARD syndrome 1. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

No clinical practice guidelines for Noonan syndrome with multiple lentigines (NSML) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with NSML, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 5. Recommended Evaluations Following Initial Diagnosis in Individuals with Noonan Syndrome with Multiple Lentigines

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

Table 7. Recommended Surveillance for Individuals with Noonan Syndrome with Multiple Lentigines

System/Concern

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for LEOPARD syndrome 1.

38 publications have been identified in PubMed for LEOPARD syndrome 1. Research spans Case Report / Case Series (53%), Review / Meta-Analysis (16%), and Basic Science / Preclinical (16%).

Research Type	Count	% of Total
Patient case studies	20	53%

Data assembled from 6 of 12 sources · Last updated Sep 19, 2026, 12:48 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:151100

Questions for Your Care Team

→Should I pursue genetic testing for PTPN11, and what would the results mean for my family?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

FAQ

Frequently Asked Questions

Common questions about LEOPARD syndrome 1

LEOPARD syndrome 1 is a rare condition that falls under the group of disorders sometimes called Noonan syndrome with multiple lentigines. The condition is defined by the presence of several small, dark spots on the skin, known as lentigines, and other features that can overlap with Noonan syndrome. People with this condition have been described with a combination of physical findings that originally led to its various names including lentiginosis and cardiomyopathic multiple lentigines syndrome.

Information about common symptoms and clinical signs is currently limited for this condition. It is noted in the condition’s description and synonyms that multiple lentigines (dark spots on the skin) are a key feature, and heart-related issues (cardiomyopathy) may be present in some cases.

LEOPARD syndrome 1 is caused by a heterozygous mutation in the PTPN11 gene located on chromosome 12q24. This genetic change affects how the protein functions and plays a role in the development of the condition. Associated genes include PTPN11.

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GeneReviews

Clinical Guidance

To date, more than 150 individuals with Noonan syndrome with multiple lentigines (NSML) have been reported. Table 2. Noonan Syndrome with Multiple Lentigines: Frequency of Select Features

Feature	Frequency	Comment
Nearly all	Common	Infrequent
Often develop after age 4-5 yrs Dysmorphic facial features	Hypertrophic cardiomyopathy	Up to 70%; may be progressive Caf au lait macules

Source: GeneReviews — "Noonan Syndrome with Multiple Lentigines"

System/Concern	Evaluation	Comment
Constitutional	Measurement of growth parameters	Consider plotting of growth parameters on population-specific growth charts Noonan syndrome growth charts.1
Cardiovascular	Echocardiogram	To assess for congenital heart defects evidence of hypertrophic cardiomyopathy Electrocardiogram
Hearing	Audiology eval2	To assess for presence type/degree of hearing loss
Eyes	Ophthalmology eval	To assess for presence of colobomata, stereopsis, abnormal eye movements3
Neurologic	Neurology eval	To incl brain MRI for those w/seizure disorders (possibly) neurodevelopmental delays
Genitourinary	Physical exam for cryptorchidism in males	Consider referral to urologist. Renal ultrasound
Development	Developmental assessment	To incl motor, adaptive, cognitive, speech-language eval; Eval for early intervention / special education
Musculoskeletal	Clinical assessment of spine rib cage	Consider radiographs referral to orthopedist if significant scoliosis or rib cage abnormalities are identified. Genetic
counseling	By genetics professionals4	To obtain a pedigree inform affected persons their families re nature, MOI, implications of NSML to facilitate medical personal decision making Family support resources
Treatment of Manifestations in Individuals with Noonan Syndrome with Multiple Lentigines Manifestation/Concern	Treatment	Considerations/Other
Short stature	Growth hormone therapy may be considered, although no data on use of growth hormone therapy in persons w/NSML exist.	Growth hormone therapy may be contraindicated in persons w/HCM.; Prior to instituting growth hormone therapy, cardiac eval for HCM is recommended; continued surveillance for development of HCM while on growth hormone therapy is reasonable.
HCM	Standard treatment per cardiologist cardiovascular surgeon	Structural heart defects
Hearing	Hearing aids may be helpful; per otolaryngologist.	Community hearing services through early intervention or school district Consider cochlear implantation for persons w/profound deafness.
abnormal eye mvmts	Standard treatment per ophthalmologist	—
Seizures	Standard treatment per neurologist	Cryptorchidism/
Genitourinary anomalies	Standard treatment per urologist	Developmental delay/
Intellectual disability	See .	Family/Community

Kisho

LEOPARD syndrome 1

Overview

Clinical Presentation

Genetic Landscape

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

OMIM

Questions for Your Care Team

Questions for Your Care Team

FAQ

Frequently Asked Questions

Clinical Guidance

Explore clinical features

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

LEOPARD syndrome 1

Overview

Clinical Presentation

Genetic Landscape

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

OMIM

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

FAQ

Frequently Asked Questions

What is LEOPARD syndrome 1?

What are the symptoms of LEOPARD syndrome 1?

What causes LEOPARD syndrome 1?

How is LEOPARD syndrome 1 inherited?

How is LEOPARD syndrome 1 diagnosed?

Are there treatments for LEOPARD syndrome 1?

What complications can arise from LEOPARD syndrome 1?

How does LEOPARD syndrome 1 affect daily life?

What is the life expectancy for someone with LEOPARD syndrome 1?

What specialists should be involved in the care of someone with LEOPARD syndrome 1?

Clinical Guidance

Explore clinical features

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications