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

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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LEOPARD Syndrome with PTPN11 Gene Mutation in Three Family Members Presenting with Different Phenotypes

Journal of Pediatric Genetics ◽

10.1055/s-0039-3400226 ◽

2019 ◽

Vol 09 (04) ◽

pp. 246-251

Author(s):

Nuha Alfurayh ◽

Fahad Alsaif ◽

Nouf Alballa ◽

Leena Zeitouni ◽

Khushnooda Ramzan ◽

...

Keyword(s):

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Family Members ◽

Leopard Syndrome ◽

Autosomal Dominant Disorder ◽

Ptpn11 Gene ◽

Ptpn11 Mutation ◽

Two Generations ◽

Generation Sequencing ◽

Multiple Lentigines

AbstractLEOPARD syndrome (LS) is a rare autosomal dominant disorder that is characterized by multiple lentigines and various congenital anomalies. The clinical diagnosis of LS requires molecular confirmation. The most frequently reported mutations in LS patients are in the protein tyrosine phosphatase nonreceptor type 11 gene, PTPN11. Herein, we report the cases of three family members from two generations who are affected by LS and all carry the PTPN11 mutation c.836A > G (p.Tyr279Cys), identified by next-generation sequencing, while exhibiting different phenotypes.

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Dermatologic Manifestations of the LEOPARD Syndrome

The Open Dermatology Journal ◽

10.2174/1874372201307010011 ◽

2013 ◽

Vol 7 (1) ◽

pp. 11-14 ◽

Cited By ~ 2

Author(s):

S. Cao ◽

A.F. Nikkels

Keyword(s):

Pulmonary Stenosis ◽

Clinical Manifestations ◽

Hypertrophic Obstructive Cardiomyopathy ◽

Leopard Syndrome ◽

Ptpn11 Gene ◽

Melanocytic Nevi ◽

Progressive Development ◽

Progressive Growth ◽

Ocular Hypertelorism ◽

Dermatologic Manifestations

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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A novel PTPN11 gene mutation bridges Noonan syndrome, multiple lentigines/LEOPARD syndrome and Noonan-like/multiple giant cell lesion syndrome

European Journal of Human Genetics ◽

10.1038/sj.ejhg.5201290 ◽

2004 ◽

Vol 12 (12) ◽

pp. 1069-1072 ◽

Cited By ~ 34

Author(s):

Anna Sarkozy ◽

Maria Gabriela Obregon ◽

Emanuela Conti ◽

Giorgia Esposito ◽

Rita Mingarelli ◽

...

Keyword(s):

Giant Cell ◽

Gene Mutation ◽

Noonan Syndrome ◽

Leopard Syndrome ◽

Ptpn11 Gene ◽

Giant Cell Lesion ◽

Multiple Lentigines

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New insights into the pathogenesis of multiple lentigines in LEOPARD syndrome with PTPN11 gene mutation

Journal of Dermatological Science ◽

10.1016/j.jdermsci.2016.08.425 ◽

2016 ◽

Vol 84 (1) ◽

pp. e142 ◽

Cited By ~ 1

Author(s):

Sei-ichiro Motegi ◽

Yoko Yokoyama ◽

Sachiko Ogino ◽

Kazuya Yamada ◽

Akihiko Uchiyama ◽

...

Keyword(s):

Gene Mutation ◽

Leopard Syndrome ◽

Ptpn11 Gene ◽

Multiple Lentigines

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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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