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Last update 08 May 2025

LEOPARD Syndrome

Last update 08 May 2025

Basic Info

Synonyms

Cardio Cutaneous Syndrome, Cardio-Cutaneous Syndrome, Cardio-Cutaneous Syndromes

+ [58]

Introduction

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.

Clinical Trials associated with LEOPARD Syndrome

NCT04395495

/ RecruitingNot ApplicableIIT

Investigation Into the Natural History and Metabolic and Molecular Basis of RASopathies.

The RASopathies are a group of developmental disorders caused by genetic changes in the genes that compose the Ras/mitogen activated protein kinase (MAPK) pathway. New RASopathies are being diagnosed frequently. This pathway is essential in the regulation of the cell cycle and the determination of cell function. Thus, appropriate function of this pathway is critical to normal development. Each syndrome in this group of disorders has unique phenotypic features, but there are many overlapping features including facial features, heart defects, cutaneous abnormalities, cognitive delays, and a predisposition to malignancies. This research study proposes to collect and store human bio-specimens from patients with suspected or diagnosed RASopathies. Once obtained, blood and/or tissue samples will be processed for: metabolic function studies, biomarkers, genetic studies, and/or the establishment of immortalized cell lines. In addition, data from the medical record (including neuropsychological evaluations) and surveys will be stored to create a longitudinal database for research conducted at CCHMC or at other research institutions.

Start Date27 Jun 2017

Sponsor / Collaborator

Children's Hospital & Medical Center

NCT02486731

/ CompletedNot ApplicableIIT

Consequences of Noonan Syndrome/LEOPARD Syndrome Associated Shp2 Mutations on Different Signaling Pathways Activation: Relationship With Hormonal Sensitivity

Noonan and LEOPARD syndromes share, with variable severity, different clinical traits, notably craniofacial manifestations, cardiopathies, short stature, and juvenile cancers.
The main genetic cause of these syndromes is missense mutation of the gene encoding the ubiquitous tyrosine phosphatase Shp2, found in more than half the patients with NS and in 80% of LS cases. Shp2 plays pivotal roles in development, growth, and metabolism by regulating key signalling pathways (Ras/Mitogen activated protein kinase (MAPK), Phosphoinositide-3 Kinases (PI3K)/Akt) in response to growth factors/hormones. Deregulation of these signalling pathways has been causally linked to NS and LS pathophysiology.
This project aims at better understanding hormonal sensitivity abnormalities in patients with Noonan syndrome (NS) or LEOPARD syndrome (LS) caused by mutations of the tyrosine phosphatase Shp2.
To reach this goal, the investigators will take advantage of different tissues (fibroblasts ± adipocytes) from patients with NS / LS compared to healthy controls.
All patients will have a skin biopsy and only patients about to undergo surgery will have a adipose tissue biopsy.

Start Date16 Dec 2015

Sponsor / Collaborator

Institut National de la Santé et de la Recherche Médicale

100 Clinical Results associated with LEOPARD Syndrome

100 Translational Medicine associated with LEOPARD Syndrome

0 Patents (Medical) associated with LEOPARD Syndrome

602

Literatures (Medical) associated with LEOPARD Syndrome

07 Feb 2025·Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery

[Perioperative management of cochlear implantation and analysis on the influencing factors of efficacy in patients diagnosed as hereditary syndromic hearing loss].

Article

Author: Yuan, Y Y ; Bi, Q L ; Yang, S M ; Han, D Y ; Gao, B ; Dai, P ; Li, X G

Objective: To explore the perioperative precautions, rehabilitation effect, and affecting factors in cochlear implantation (CI) among patients with hereditary syndromic hearing loss. Methods: This was a retrospective cohort study. 47 patients diagnosed as hereditary syndromic deafness were treated in the Department of Otolaryngology-Head and Neck Surgery of the Chinese PLA General Hospital from 2010 to 2021, including 26 males and 21 females, aged 0.9-25 years. All patients received unilateral or bilateral CI. Clinical manifestation combined with genetic testing was used to diagnose syndromic hearing loss. The risks and precautions of CI in these patients were summarized from preoperative imaging, intraoperative observations, and postoperative complications. Single factor linear regression and multiple linear regression models in SPSS 26.0 software were used to evaluate the effects of various factors on auditory and speech rehabilitation after CI for syndromic hearing loss. The postoperative outcomes were analyzed through aided hearing thresholds, categories of auditory performance (CAP) scale, and speech intelligibility rate (SIR) scale. Results: Thirteen kinds of syndromes, totally 47 cases, including CHARGE (20 cases), Waardenburg (9 cases), Autosomal dominant deafness-onychodystrophy (DDOD, 4 cases), Pendred (3 cases), Noonan Syndrome with Multiple Lentigines (NSML, 2 cases), Branchio-Oto-Renal (BOR, 2 cases), Bart-Pumphery (1 case), Perrault (1 case), Kabuki (1 case), Frontometaphyseal dysplasia type 2 (FMD 2, 1 case), Mandibulofacial dysostosis Guion-Almeida type (MFDGA, 1 case), Coffin-Siris (1 case), and 10q26.12-q26.3 del (1 case), were enrolled. The perioperative special management included the following measures. For patients with cardiac and/or cartilage development issues, preoperative assessments of cardiac function and/or laryngeal cartilage development were performed to minimize anesthetic risks. For patients with mild intellectual disability and/or an auditory neuropathy phenotype, preoperative communication with the patients' families was conducted to explain the limitations of CI and assist in setting reasonable expectations. For syndromic hearing loss patients who commonly present with inner ear malformations, facial nerve anomalies, and/or intraoperative cerebrospinal fluid leakage, appropriate electrodes were selected prior to surgery, intraoperative facial nerve monitoring and careful cerebrospinal fluid leak repair were conducted, respectively. For patients with NSML accompanied by coagulation issues, the postoperative compression bandaging duration was extended to reduce the risk of hematoma formation. The daily duration of cochlear implant use, the presence of cochlear malformation, and developmental delay were independent factors influencing postoperative CAP scores. The daily duration of cochlear implant use, developmental delay, and unilateral or bilateral CI were independent factors influencing postoperative SIR scores. Conclusions: Hereditary syndrome deafness is a rare disease that affects multiple organs and causes extensive functional impairment. Before CI, a comprehensive evaluation of major affected organ functions is required to assess anesthetic and surgical risks. Genetic diagnosis not only identifies the molecular etiology of patients with syndromic hearing loss and reveals rare phenotypes, but also aids in prognostic evaluation. The main factors affecting CI outcomes in patients with syndromic hearing loss include the presence of cochlear malformations, developmental delays, daily duration of cochlear implant use, and bilateral implantation status.

01 Feb 2025·JACC: Advances

Naxos Disease and Related Cardio-Cutaneous Syndromes

Review

Author: Vasilakis, Anargyros ; Syrris, Petros ; Monda, Emanuele ; Asimaki, Angeliki ; Cadrin-Turigny, Julia ; Protonotarios, Ioannis ; Limongelli, Giuseppe ; Gaetano Thiene, Stamatios ; Carbone, Andreina ; Kaski, Juan Pablo ; Xylouri, Zafeirenia ; McKenna, William J ; Lerakis, Stamatis ; Anastasakis, Aris ; Saffitz, Jeffrey E ; Papadopoulos, George ; Antoniades, Loizos ; Gimeno, Juan Ramon ; S Coonar, Aman ; Bakalakos, Athanasios ; Prandi, Francesca Romana ; Basso, Cristina ; Elliott, Perry M ; Tsatsopoulou, Adalena ; Pecchia, Leandro ; Bossone, Eduardo ; Abrahms, Dominic Jr ; Crisci, Giulia ; Mestroni, Luisa ; Lazaros, George ; Protonotarios, Alexandros

Naxos disease is a rare autosomal recessive condition combining arrhythmogenic right ventricular cardiomyopathy, woolly hair, and palmoplantar keratoderma. The first identified causative variant was in the gene encoding the desmosomal protein plakoglobin. Naxos disease exhibits fibro-fatty myocardial replacement with immunohistological abnormalities in cardiac protein and signaling pathways, highlighting the role of inflammation and potential anti-inflammatory treatments. Childhood cutaneous signs precede cardiac features, which are diagnosed by familial and genetic evaluation, electrocardiography and cardiac imaging. Disease progression necessitates holistic care with risk management and lifestyle adjustments, often needing treatment for arrhythmia and heart failure. Similar phenotypes have been linked to desmoplakin and rarely desmocollin2 gene variants, highlighting the importance of familial and genetic evaluation. This document summarizes current knowledge on Naxos disease and related cardiocutaneous syndromes and initiates an international endeavor to collect and study all global cases, aiming to improve understanding, treatment, and patient care through shared data and research.

01 Feb 2025·International Journal of Developmental Neuroscience

A patient with a PTPN11 gene variant complicated with Chiari I malformation and syringomyelia and a review of literatures

Review

Author: Yang, Chengqing ; Yi, Zhi ; Li, Fei ; Xue, Jiao ; Song, Zhenfeng ; Zhang, Ying

AbstractBackgroundAccording to previous literature reports, PTPN11 gene variants account for approximately 50% of Noonan syndrome (NS) cases and 85% of Leopard syndrome (LS) cases. Several patients who were diagnosed with NS or LS complicated with Chiari I malformation (CIM) and/or syringomyelia have been reported to have a PTPN11 variant. However, it is not always clear whether the association between CIM and/or syringomyelia and PTPN11 variants is real or random. We try to explain this phenomenon by reporting a clinical case and making a mini‐review.MethodsWe retrospectively described a clinical case in detail and made a genetic test on the proband and her family members using whole‐exome sequencing. And made a review of the related literatures.ResultsThe patient was manifesting progressive abnormal gait and muscle weakness for more than 2 years before she was admitted to our hospital at the age of 5 years and 2 months. On examination, she looked frail and slender. She had short stature, mild intellectual disability, decreased muscle strength in the left limb, thinner left limb, left hollow foot and foot drop, weakened left knee and Achilles tendon reflexes and a positive left Babinski sign. She looked timid and had very little expressive language. MRI of the brain and spine revealed CIM and syringomyelia with hydrops. Cardiac ultrasonography revealed an ostium secundum defect. ECG examination showed no abnormalities. She received a spinal cavity subarachnoid shunt; the symptoms were relieved to some extent, and the cavity in the lumbar vertebrae was significantly reduced after the surgery. Genetic testing found a variant, c. 922A>G (p. Asn308Asp) in the PTPN11 gene. Both parents were wild‐type at this locus. A literature review found that 31 patients with NS or LS were complicated with CIM, syringomyelia or both. Together with our patient, a total of six patients in this group had the PTPN11 gene variant. Among them, four were complicated with both CIM and syringomyelia, and two were complicated with CIM only.ConclusionsWe report another case with a PTPN11 variant that was complicated with both CIM and syringomyelia. It suggests that CIM and syringomyelia may be clinical manifestations of PTPN11 variation‐related diseases. This phenomenon may be underrated due to limitations of genetic diagnostic methods in the past. We strongly suggest routine craniocerebral and spinal MRI scans and genetic testing for patients suspected of having NS or LS.

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