Dermatologic Manifestations of the LEOPARD Syndrome

The LEOPARD syndrome is an exceptional autosomal dominant genetic disease with a missense mutation of the PTPN11 gene in more than 90% of the cases. The principal clinical manifestations include extensive lentiginosis, heart conduction abnormalities, hypertrophic obstructive cardiomyopathy, ocular hypertelorism, pulmonary stenosis, genital anomalies, mental retardation, growth retardation and deafness. A woman with a LEOPARD syndrome illustrates the progressive development of melanocytic nevi. In fact, the majority of lentigines are actually melanocytic nevi. Sequential digital dermoscopy evidences progressive growth of some melanocytic lesions. The ever-increasing number of melanocytic nevi in the LEOPARD syndrome is a risk factor for melanoma and full body photography and dermoscopy are recommended for follow-up.

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Leopard syndrome: the potential cardiac defect underlying skin phenotypes

Hereditas ◽

10.1186/s41065-021-00199-5 ◽

2021 ◽

Vol 158 (1) ◽

Author(s):

Xiaojie Yue ◽

Xiong Zhao ◽

Yefeng Dai ◽

Lan Yu.

Keyword(s):

Early Stage ◽

Pulmonary Stenosis ◽

Pathological Examination ◽

Leopard Syndrome ◽

Cardiac Damage ◽

Melanocytic Nevi ◽

Café Au Lait Spots ◽

Potential Damage ◽

Ocular Hypertelorism ◽

Multiple Lentigines

AbstractLEOPARD syndrome (OMIM #151,100) caused by a germline PTPN11 mutation are characterized as multisystemic anomalies and variable marked phenotypes such as multiple lentigines and cafe´-au-lait spots, electrocardiographic conduction abnormalities, ocular hypertelorism/obstructive cardiomyopathy, pulmonary stenosis, abnormal genitalia, retardation of growth, and deafness. Phenotype overlap complicates clinical discrimination within RASopathies, making the diagnosis of LEOPARD more confusing and challenging. Besides, LEOPARD patients do not usually present with all these typical clinical features, increasing the possibility of underdiagnosis or misdiagnosis.Herein, we report a case of LEOPARD syndrome in a patient who only presented with pigmented skin spots and was initially diagnosed with multiple acquired melanocytic nevi. Subsequent pathological examination confirmed the diagnosis of multiple lentigines rather than melanocytic nevi. A genetic study showed a germline PTPN11 (Tyr279Cys) mutation and raised the suspicion of LEOPARD syndrome. A subsequent ECG examination detected potential cardiac defects and confirmed the diagnosis of LEOPARD. We considered that the potential damage of other systems underlying the skin multiple lentigines should not be ignored. The diagnosis of LEOPARD syndrome in an early stage before cardiac damage has reached a serious and irreversible stage can be meaningful for patients to fully understand the potential risks, complications and prognosis of the disease and to take appropriate precautions to prevent the potential risk of cardiac damage.

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The First Vietnamese Patient of LEOPARD Syndrome due to a PTPN11 Mutation: A Case Report and Review of the Literature

Case Reports in Genetics ◽

10.1155/2021/8197435 ◽

2021 ◽

Vol 2021 ◽

pp. 1-5

Author(s):

Hao Trong Nguyen ◽

Nguyen Nhat Pham ◽

Hoang Anh Vu ◽

Tu Nguyen Anh Tran

Keyword(s):

Pulmonary Valve ◽

Ho Chi Minh City ◽

City Hospital ◽

Leopard Syndrome ◽

Ptpn11 Gene ◽

Ptpn11 Mutation ◽

First Case ◽

Brownish Black ◽

Ocular Hypertelorism ◽

Multiple Lentigines

LEOPARD syndrome is a rare congenital anomaly that involves several organs. Patients with this syndrome develop multiple lentigines resembling a leopard’s hide. LEOPARD is an acronym of the major features constituting the syndrome including lentigines, electrocardiographic conduction defects, ocular hypertelorism, pulmonary valve stenosis, anomalies of genitalia, retardation of growth, and deafness. The syndrome is rare, and only 200 cases have been reported yet worldwide. We present the case of an 8-year-old female patient who visited the Ho Chi Minh City Hospital of Dermato-Venereology because of multiple brownish-black “dots” on her face and body. On examination, she also showed abnormalities in the maxillofacial bones, vertebrae, shoulders, sternum, and teeth, as well as deaf-mutism and growth retardation, which are typical of LEOPARD syndrome. Genetic analysis revealed a PTPN11 gene mutation in this case. To the best of our knowledge, this is the first case of LEOPARD syndrome reported in Vietnam.

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Gangguan pendengaran pada sindroma LEOPARD

Oto Rhino Laryngologica Indonesiana ◽

10.32637/orli.v42i2.23 ◽

2012 ◽

Vol 42 (2) ◽

Author(s):

Semiramis Zizlavsky ◽

Ronny Suwento ◽

Dina Alia

Keyword(s):

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Pulmonary Stenosis ◽

Sensorineural Deafness ◽

Sensorineural Hearing ◽

Leopard Syndrome ◽

Brainstem Evoked Response Audiometry ◽

Delayed Onset ◽

Ocular Hypertelorism ◽

Evoked Response Audiometry

Background: Leopard syndrome is a rare case, only around 200 cases has been reported worldwide. Leopard syndrome is abbreviation for multipel Lentigines, Electrocardiographic conduction, Ocular hypertelorism, Pulmonary stenosis, Abnormality of genitalia, Retardation of growth, and sensorineural Deafness. This disorder suggests a possible relation between PTPN11 gene mutations and distinct clinical features. Purpose: This case is presented so that ENT specialists could identify signs and symptoms of Leopard Syndrome which manifest as sensorineural hearing loss (SNHL). Case: We report a 29 year old woman with multiple lentigines, scoliosis and atrial septal defect. She has 4 year old twin boys, one of them has cryptorchidism and a 10 month old girl with asymmetric septal hypertrophy and they also have multipel lentigines. They were referred to ENT Department for auditory function screening since Leopard syndrome is suspected. The audiometry of the mother reveals mild conductive deafness (40 dB) in right ear due to tympanic membrane perforation. Audiometry of the twin boys reveals sensorineural hearing loss above 4000 Hz frequency. Brainstem Evoked Response Audiometry (BERA) of the daughter reveals mild sensorineural hearing loss (40 dB )on right ear. Genogram shows that the disorders is dominant autosomal inherited. Management: Periodic auditory examination for sensorineural hearing loss is recommended since delayed onset could occur. Conclusion: Sensorineural hearing loss is a mani-festation of Leopard syndrome that should be assessed early and periodically to detect delayed onset. Keywords: Sensorineural hearing loss (SNHL), Leopard syndrome, generalized lentiginosa. Abstrak : Latar belakang: Sindroma Leopard merupakan kasus yang jarang ditemukan dan dari publikasi yang ada, hingga saat ini hanya terdapat 200 kasus di seluruh dunia. Sindroma Leopard merupakan singkatandari Lentigines multipel, Electrocardiographic conduction, Ocular hypertelorism, Pulmonary stenosis,Abnormality of genitalia, Retardation of growth and sensorineural Deafness. Kelainan ini disebabkan olehmutasi gen PTPN11 dengan gambaran klinis yang khas. Tujuan: Kasus ini diajukan agar spesialis THTmengenali gejala sindroma Leopard yang dapat melibatkan gangguan pendengaran berupa sensorineuralhearing loss(SNHL) sehingga tidak terjadi keterlambatan dalam penatalaksanaan. Kasus: Perempuanberusia 29 tahun dengan lentiginosa multipel, skoliosis dan defek septum atrium. Ia memiliki 2 anaklaki-laki kembar yang salah satunya mengalami kriptorkismus dan anak perempuan usia 10 bulan yangmenderita hipertrofi septum asimetris dan juga menderita multipel lentiginosa. Mereka dikonsulkan ke THT dari bagian kulit RSCM untuk pemeriksaan fungsi pendengaran dengan kecurigaan sindromaLeopard. Pada pemeriksaan audiometri diperoleh hasil pada ibu berupa tuli konduktif ringan (40 dB)telinga kanan akibat perforasi membran timpani. Dua orang anak kembar menunjukkan hasil tuli sarafdi atas frekuensi 4000 Hz. Pemeriksaan Brainstem Evoked Response Audiometry (BERA) pada anakperempuan menunjukkan tuli saraf ringan (40 dB) di telinga kanan. Genogram menunjukkan kelainanautosom dominan. Penatalaksanaan: Tindak lanjut berupa pemeriksaan pendengaran secara berkaladianggap penting untuk mendeteksi terjadinya awitan lambat. Kesimpulan: SNHL merupakan salah satumanifestasi sindroma Leopard yang perlu diperiksa untuk mendeteksi terjadi awitan lambat. Kata kunci: Sensorineural hearing loss (SNHL), sindroma Leopard, lentiginosa multipel.

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Phosphatase-defective LEOPARD syndrome mutations in PTPN11 gene have gain-of-function effects during Drosophila development

Human Molecular Genetics ◽

10.1093/hmg/ddn336 ◽

2008 ◽

Vol 18 (1) ◽

pp. 193-201 ◽

Cited By ~ 56

Author(s):

Kimihiko Oishi ◽

Hui Zhang ◽

William J. Gault ◽

Cindy J. Wang ◽

Cheryl C. Tan ◽

...

Keyword(s):

Leopard Syndrome ◽

Gain Of Function ◽

Ptpn11 Gene ◽

Drosophila Development

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Central giant cell lesions with an unusual behavior in patient with Noonan syndrome: A case report with 8-year follow-up

Research Society and Development ◽

10.33448/rsd-v10i1.11563 ◽

2021 ◽

Vol 10 (1) ◽

pp. e13510111563

Author(s):

Gleysson Matias de Assis ◽

Marcelo Leite Machado da Silveira ◽

José Wittor de Macêdo Santos ◽

Humberto Pereira Chaves Neto ◽

Lucas Melo da Costa ◽

...

Keyword(s):

Giant Cell ◽

Noonan Syndrome ◽

Pulmonary Stenosis ◽

Clinical Information ◽

Patient Discharge ◽

Blood Analysis ◽

Unusual Behavior ◽

Ptpn11 Gene ◽

Mandibular Injuries

This study describes a patient with Noonan syndrome affected by multiple Central Giant Cell Lesions (CGCL) in jaws. The lesions presented an unusual behavior since there was no regression size after puberty. The syndrome was diagnosed by collecting clinical information, represented by ocular hypertelorism, low insertion of ears, pulmonary stenosis, cryptorchidism, cardiac abnormalities, short stature, multiple CGCL in the jaws, and blood analysis that found a mutation of the PTPN11 gene. The treatment consisted of systemic calcitonin for a period of 14 months and three surgical procedures at distinct moments. The patient is currently with 20 years and in the eighth-year of follow-up. Although he presented an improvement in deformity, radiological findings showed remodeling without resolution of mandibular injuries, making it clear that injuries will did not always regress after puberty and not confirm previously publications in the literature. We therefore advocate a larger time of follow-up before patient discharge in these cases.

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LEOPARD Syndrome Without Hearing Loss or Pulmonary Stenosis: A Report of 2 Cases

Actas Dermo-Sifiliográficas (English Edition) ◽

10.1016/j.adengl.2015.03.006 ◽

2015 ◽

Vol 106 (4) ◽

pp. e19-e22

Author(s):

T.T. Ramos-Geldres ◽

P. Dávila-Seijo ◽

A. Duat-Rodríguez ◽

L. Noguera-Morel ◽

B. Ezquieta-Zubicaray ◽

...

Keyword(s):

Hearing Loss ◽

Pulmonary Stenosis ◽

Leopard Syndrome

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PROPTOSIS AND DIPLOPIA AS CONSEQUENCES IN TRAUMA OF CRANIOFACIAL JUNCTION

Facta Universitatis Series Medicine and Biology ◽

10.22190/fumb170517006p ◽

2017 ◽

pp. 038

Author(s):

Srbislav Pajić ◽

Tanja Boljević ◽

Svetlana Antić ◽

Milutin Mrvaljević ◽

Milena Cojić ◽

...

Keyword(s):

Frontal Sinus ◽

Bone Fractures ◽

Clinical Manifestations ◽

High Energy ◽

Late Complications ◽

Common Mechanism ◽

Energy Impact ◽

Ophthalmic Manifestations ◽

Sinus Wall ◽

Progressive Growth

In the trauma of craniofacial junction, frontal sinus wall fractures take up 5-15% of all facial bone fractures. The most common mechanism of their occurrence comes as a result of the action of high-energy impact force on the frontal area. Treatment of the injuries in frontal-orbital-ethmoidal regions largely depends on the responsible experts (otolaryngologist, maxillofacial surgeon or neurosurgeon) in all cases, because of the implementation of diverse surgical technics in order to achieve the best possible outcome for the patient. Bearing in mind the complex anatomical features of this region, it is clear that these procedures are often accompanied by series of possible complications, all of which are certainly neurosurgical. These can be expressed as early or late complications, and could be characterized by diverse clinical manifestations. Mucocele is formed, either due to partial obstruction of the sinus mucosa or due to the obstruction of the frontal sinus. The long term existence of mucocele and its progressive growth will result in strong pressure on the adjacent bones, and lead to their destruction followed by the process-propagation into surrounding tissues and spaces. In the further development if a bacterial contamination is detected, it will lead to the purulent inflammatory process and clinical picture of mucopyocele. In most clinical cases with complications proptosis and diplopia are dominant ophthalmic manifestations. In this paper we will present our experience in the treatment of proptosis and diplopia, as well as the ways of diagnostic evaluation in order to achieve timely diagnosis and assure swift healing of patients.

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