LEOPARD Syndrome (Syndrome, LEOPARD)

An autosomal dominant disorder with an acronym of its seven features (LENTIGO; ELECTROCARDIOGRAM abnormalities; ocular HYPERTELORISM; PULMONARY STENOSIS; abnormal genitalia; retardation of growth; and DEAFNESS or SENSORINEURAL HEARING LOSS). This syndrome is caused by mutations of PTPN11 gene encoding the non-receptor PROTEIN TYROSINE PHOSPHATASE, type 11, and is an allelic to NOONAN SYNDROME. Features of LEOPARD syndrome overlap with those of NEUROFIBROMATOSIS 1 which is caused by mutations in the NEUROFIBROMATOSIS 1 GENES.

Also Known As:

Syndrome, LEOPARD; Cardio-Cutaneous Syndrome; Cardiomyopathic Lentiginosis; LEOPARD Syndrome, 1; Lentiginosis Cardiomyopathic; Leopard Syndrome 1; Multiple Lentigines Syndrome; Noonan Syndrome with Multiple Lentigines; Progressive Cardiomyopathic Lentiginosis; Cardio Cutaneous Syndrome; Cardio-Cutaneous Syndromes; Cardiomyopathic Lentiginoses; Cardiomyopathic Lentiginoses, Progressive; Cardiomyopathic Lentiginosis, Progressive; Cardiomyopathic, Lentiginosis; Cardiomyopathics, Lentiginosis; LEOPARD Syndromes; Lentigines Syndrome, Multiple; Lentigines Syndromes, Multiple; Lentiginoses, Cardiomyopathic; Lentiginoses, Progressive Cardiomyopathic; Lentiginosis Cardiomyopathics; Lentiginosis, Cardiomyopathic; Lentiginosis, Progressive Cardiomyopathic; Multiple Lentigines Syndromes; Progressive Cardiomyopathic Lentiginoses; Syndrome, Cardio-Cutaneous; Syndrome, Multiple Lentigines; Syndromes, Cardio-Cutaneous; Syndromes, LEOPARD; Syndromes, Multiple Lentigines

Networked: 62 relevant articles (2 outcomes, 3 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Hypertrophic Cardiomyopathy (Hypertrophic Obstructive Cardiomyopathy)
2.	Costello Syndrome
3.	Neurofibromatosis 1 (Neurofibromatosis Type I)
4.	Cardiofaciocutaneous syndrome
5.	Cardiomegaly (Heart Hypertrophy)

Experts

1.	Tartaglia, Marco: 7 articles (01/2021 - 02/2006)
2.	Kontaridis, Maria I: 7 articles (01/2018 - 05/2010)
3.	Gelb, Bruce D: 7 articles (04/2015 - 02/2006)
4.	Martinelli, Simone: 4 articles (01/2021 - 02/2006)
5.	Neel, Benjamin G: 4 articles (01/2018 - 05/2010)
6.	Lauriol, Jessica: 4 articles (01/2016 - 03/2011)
7.	Krenz, Maike: 3 articles (05/2015 - 06/2013)
8.	Bocchinfuso, Gianfranco: 2 articles (01/2021 - 02/2006)
9.	Flex, Elisabetta: 2 articles (01/2021 - 02/2006)
10.	Pannone, Luca: 2 articles (01/2021 - 09/2014)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to LEOPARD Syndrome:

1.	Dasatinib (BMS 354825)FDA Link 01/01/2022 - "Low-dose Dasatinib Ameliorates Hypertrophic Cardiomyopathy in Noonan Syndrome with Multiple Lentigines."
2.	MiransertibIBA 01/01/2017 - "In vivo efficacy of the AKT inhibitor ARQ 092 in Noonan Syndrome with multiple lentigines-associated hypertrophic cardiomyopathy."
3.	Phosphoric Monoester Hydrolases (Phosphatases)IBA 04/12/2013 - "Our study reveals that LEOPARD syndrome mutations weaken the intramolecular interaction between the N-SH2 and phosphatase domains, leading to a change in SHP2 molecular switching mechanism. " 05/18/2010 - "Phosphatase-dependent and -independent functions of Shp2 in neural crest cells underlie LEOPARD syndrome pathogenesis." 01/01/2009 - "Phosphatase-defective LEOPARD syndrome mutations in PTPN11 gene have gain-of-function effects during Drosophila development." 05/01/2006 - "Reduced phosphatase activity of SHP-2 in LEOPARD syndrome: consequences for PI3K binding on Gab1." 04/12/2013 - "Interestingly, Noonan syndrome SHP2 mutants are constitutively active, whereas LEOPARD syndrome SHP2 mutants exhibit reduced phosphatase activity. "
4.	Mitogen-Activated Protein KinasesIBA 05/01/2015 - "LEOPARD syndrome is an autosomal dominant disease caused by germline mutations in the RAS-MAPK (mitogen-activated protein kinase) pathway. " 09/01/2014 - "The RASopathies are a relatively common group of phenotypically similar and genetically related autosomal dominant genetic syndromes caused by missense mutations affecting genes participating in the RAS/mitogen-activated protein kinase (MAPK) pathway that include Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML, formerly LEOPARD syndrome). " 06/10/2010 - "We have generated iPSCs from patients with LEOPARD syndrome (an acronym formed from its main features; that is, lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary valve stenosis, abnormal genitalia, retardation of growth and deafness), an autosomal-dominant developmental disorder belonging to a relatively prevalent class of inherited RAS-mitogen-activated protein kinase signalling diseases, which also includes Noonan syndrome, with pleomorphic effects on several tissues and organ systems. " 01/01/2009 - "In recent years, germline mutations that affect components of the RAS-MAPK (mitogen-activated protein kinase) pathway were shown to be involved in the pathogenesis of NS and four rare syndromes with clinical features overlapping with NS: Leopard syndrome, cardio-facio-cutaneous syndrome, Costello syndrome and neurofibromatosis type 1. Several hormones act through receptors that stimulate the RAS-MAPK pathway, and therefore, NS and related disorders represent a remarkable opportunity to study the implication of the RAS-MAPK pathway in different endocrine systems. "
5.	TOR Serine-Threonine KinasesIBA 11/13/2019 - "Animal studies suggested that blocking the activation of the mammalian target of rapamycin (mTOR) pathway might be effective to treat cardiac hypertrophy in LEOPARD syndrome (LS) caused by PTPN11 mutations. "
6.	Hormones (Hormone)IBA 01/01/2009 - "In recent years, germline mutations that affect components of the RAS-MAPK (mitogen-activated protein kinase) pathway were shown to be involved in the pathogenesis of NS and four rare syndromes with clinical features overlapping with NS: Leopard syndrome, cardio-facio-cutaneous syndrome, Costello syndrome and neurofibromatosis type 1. Several hormones act through receptors that stimulate the RAS-MAPK pathway, and therefore, NS and related disorders represent a remarkable opportunity to study the implication of the RAS-MAPK pathway in different endocrine systems. "
7.	Protein Tyrosine PhosphatasesIBA 01/01/2016 - "Loss-of-function mutations in PTPN11, which encodes the protein tyrosine phosphatase (PTP) SHP2, are implicated in CHD and cause Noonan syndrome with multiple lentigines (NSML), a condition that often presents with cardiac hypertrophic defects. " 03/14/2014 - "Structural insights into Noonan/LEOPARD syndrome-related mutants of protein-tyrosine phosphatase SHP2 (PTPN11)." 12/01/2007 - "We generated mutants of Shp2 with mutations that were identified in human patients with Noonan or LEOPARD Syndrome and established that Noonan Shp2 was activated and LEOPARD Shp2 lacked catalytic protein-tyrosine phosphatase activity. " 03/01/2006 - "Mutations in PTPN11, a gene encoding the protein tyrosine phosphatase SHP-2 located on chromosome 12q24.1, have been identified in 88% of patients with LEOPARD syndrome. " 02/01/2004 - "Mutations in PTPN11, a gene encoding the protein tyrosine phosphatase SHP-2 located at chromosome 12q24, have been identified in patients with LEOPARD syndrome. "
8.	Tyrosine (L-Tyrosine)FDA Link 05/01/2010 - "LEOPARD syndrome (LS), a disorder with multiple developmental abnormalities, is mainly due to mutations that impair the activity of the tyrosine phosphatase SHP2 (PTPN11). " 11/15/2020 - "LEOPARD syndrome most frequently develops secondary to a missense mutation of protein-tyrosine phosphatase nonreceptor type 11 gene, which encodes tyrosine phosphatase. " 10/01/2015 - "Over the two past decades, mutations of the PTPN11 gene, encoding the ubiquitous protein tyrosine phosphatase SHP2 (SH2 domain-containing tyrosine phosphatase 2), have been identified as the causal factor of several developmental diseases (Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NS-ML), and metachondromatosis), and malignancies (juvenile myelomonocytic leukemia). "
9.	Proteins (Proteins, Gene)FDA Link 07/01/2020 - "NS and other clinically overlapping conditions such as NS with multiple lentigines (formerly called LEOPARD syndrome), cardiofaciocutaneous syndrome, or Costello syndrome, are caused by mutations in genes encoding proteins of the RAS-MAPKinases pathway. " 10/01/2017 - "Alterations in autophagy have been reported in hypertrophic cardiomyopathy (HCM) caused by Danon disease, Vici syndrome, or LEOPARD syndrome, but not in HCM caused by mutations in genes encoding sarcomeric proteins, which account for most of HCM cases. " 01/01/2020 - "P0-related protein (PZR), a Noonan and Leopard syndrome target, is a member of the transmembrane Immunoglobulin superfamily. "
10.	Non-Receptor Type 11 Protein Tyrosine PhosphataseIBA 05/01/2010 - "LEOPARD syndrome (LS), a disorder with multiple developmental abnormalities, is mainly due to mutations that impair the activity of the tyrosine phosphatase SHP2 (PTPN11). " 05/18/2010 - "Paradoxically, Noonan syndrome mutations increase SHP2 phosphatase activity, while LEOPARD syndrome mutants are catalytically impaired, raising the possibility that SHP2 has phosphatase-independent roles. "

Therapies and Procedures

1.	Cochlear Implantation 01/01/2022 - "Cochlear implantation in LEOPARD syndrome: Our experience with three patients." 11/01/2016 - "Bilateral cochlear implantation in the case of a child with Leopard syndrome can be successful." 11/01/2016 - "The experience of bilateral cochlear implantation in a child with LEOPARD syndrome." 06/01/2017 - "Existing literature only reports a few patients with Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) who underwent cochlear implantation (CI). " 06/01/2017 - "Cochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11."
2.	Implantable Defibrillators (Implantable Cardioverter-Defibrillator) 10/01/2011 - "Implantable cardioverter defibrillator for progressive hypertrophic cardiomyopathy in a patient with LEOPARD syndrome and a novel PTPN11 mutation Gln510His." 11/15/2020 - "The recognition of increased left or right ventricular wall thickness in patients with LEOPARD syndrome may have significant impact on their clinical course similar to classic hypertrophic cardiomyopathy, which may require septal reduction procedures for relief of left or right ventricular outflow tract obstruction or implantable cardioverter-defibrillator placement for sudden cardiac death prevention. "
3.	Anesthesia 10/01/2014 - "The medical and anesthesia records of patients with LEOPARD syndrome were reviewed. " 10/01/2014 - "The purpose of this case series was to review the most prominent comorbidities associated with LEOPARD syndrome, and describe perioperative outcomes in a series of patients undergoing anesthesia. " 10/01/2003 - "[ECG changes during emergence from anesthesia in a patient with LEOPARD syndrome]." 10/01/2014 - "Nine patients with LEOPARD syndrome underwent 49 procedures under general anesthesia (n = 40) or monitored anesthesia care (n = 9). " 10/01/2014 - "Retrospective case series review Tertiary care institution Patients diagnosed with LEOPARD syndrome who underwent surgical procedures requiring anesthesia at this institution. "
4.	Vitrectomy 03/01/2023 - "OPTIC DISK COLOBOMA AND CONTRALATERAL OPTIC DISK PIT MACULOPATHY TREATED BY VITRECTOMY IN A PATIENT WITH NOONAN SYNDROME WITH MULTIPLE LENTIGINES."
5.	Therapeutics 12/01/2008 - "Volar melanotic macules can also complicate 5-flourouracil therapy, tinea pedis, and other inflammatory disorders; be associated with acral melanomas; or represent a cutaneous manifestation of systemic disease such as Addison disease, Peutz-Jegher syndrome, Leopard syndrome, Carney syndrome, AIDS, and neurofibromatosis."