How is LEOPARD syndrome 3 inherited?

LEOPARD syndrome 3 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 3 diagnosed?

Information about diagnosis is currently limited for this condition.

Are there treatments for LEOPARD syndrome 3?

Information about treatment is currently limited for this condition.

What complications can arise from LEOPARD syndrome 3?

Currently, information about complications specific to LEOPARD syndrome 3 is limited. However, since it is part of the Noonan syndromes, individuals may experience health issues related to heart function, growth, and skin appearance. Regular check-ups with healthcare providers can help monitor and manage any potential complications.

How might LEOPARD syndrome 3 affect daily life?

LEOPARD syndrome 3 can affect daily life in various ways, especially due to its skin features and possible health issues. Individuals may need to manage their skin appearance and may require regular medical visits for monitoring. Support from family and friends can be important in navigating daily challenges.

What is the life expectancy for someone with LEOPARD syndrome 3?

Information about life expectancy for individuals with LEOPARD syndrome 3 is currently limited. Since this condition is part of the Noonan syndromes, life expectancy can vary based on the presence of other health issues. Regular medical care and monitoring can help improve health outcomes.

Are there any specialists recommended for managing LEOPARD syndrome 3?

While specific specialists for LEOPARD syndrome 3 are not detailed, individuals may benefit from seeing a geneticist or a specialist in Noonan syndromes. These experts can provide guidance on managing symptoms and coordinating care. Regular visits to healthcare providers can help ensure comprehensive support.

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LEOPARD syndrome 3 - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

LEOPARD syndrome 3

MONDO:0013380

Also known as:BRAF Noonan syndrome with multiple lentiginesLeopard syndrome type 3Noonan syndrome with multiple lentigines caused by mutation in BRAF

Overview

Any Noonan syndrome with multiple lentigines in which the cause of the disease is a mutation in the BRAF gene.

GeneticsAutosomal dominant · BRAF (chr 7)

OnsetJUVENILE

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: Narrow forehead, Short stature, Seizure, and Numerous nevi and others; and common findings: Tetralogy of Fallot. 32 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	3	Seizure, Intellectual disability, Depressed nasal bridge

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.

BRAF encodes B-Raf proto-oncogene, serine/threonine kinase (766 aa). Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Highest expression in Brain Cerebellar Hemisphere (27.6 TPM) and Brain Cerebellum (21.5 TPM).

LEOPARD syndrome 3 is associated with mutations in the BRAF gene on chromosome 7.

The BRAF protein participates in BRAF inhibitors:high kinase activity BRAF mutants pathway.

BRAF is classified as a druggable target (Clinically Actionable, Drug Resistance, Druggable Genome, Enzyme, Kinase, and Serine Threonine Kinase categories) with score 2.5.

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 3. 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 3.

15 publications have been identified in PubMed for LEOPARD syndrome 3. Research spans Case Report / Case Series (53%), Basic Science / Preclinical (20%), and Review / Meta-Analysis (13%).

Research Type	Count	% of Total
Patient case studies	8	53%

Data assembled from 6 of 12 sources · Last updated Sep 19, 2026, 1:53 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:613707

GARD

Genetic and Rare Diseases Info Center

GARD:15694

Questions for Your Care Team

→Should I pursue genetic testing for BRAF, 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 3

LEOPARD syndrome 3 is a rare genetic condition that falls under the group of Noonan syndromes with multiple lentigines. It is caused by a mutation in the BRAF gene. People with this condition may have differences in skin appearance and other characteristics typical of Noonan syndromes with multiple lentigines. The condition is known by several names including BRAF Noonan syndrome with multiple lentigines and Leopard syndrome type 3. Although details about its full clinical picture are still being studied, this summary is based on verified scientific sources.

Information about symptoms is currently limited for this condition.

LEOPARD syndrome 3 is caused by a mutation in the BRAF gene. BRAF is known to play a role in cell growth and development, and changes in this gene can lead to the distinct features seen in this syndrome. Associated genes include BRAF.

← Back to All Diseases

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 3

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

OMIM

GARD

Questions for Your Care Team

Questions for Your Care Team

FAQ

Frequently Asked Questions

Clinical Guidance

Explore clinical features

Clinical Guidance

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

LEOPARD syndrome 3

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

OMIM

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

FAQ

Frequently Asked Questions

What is LEOPARD syndrome 3?

What are the symptoms of LEOPARD syndrome 3?

What causes LEOPARD syndrome 3?

How is LEOPARD syndrome 3 inherited?

How is LEOPARD syndrome 3 diagnosed?

Are there treatments for LEOPARD syndrome 3?

What complications can arise from LEOPARD syndrome 3?

How might LEOPARD syndrome 3 affect daily life?

What is the life expectancy for someone with LEOPARD syndrome 3?

Are there any specialists recommended for managing LEOPARD syndrome 3?

Clinical Guidance

Explore clinical features

Clinical Guidance

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications