A 'Full House' Glomerulopathy in a Patient with Multiple Lentigines Syndrome: A Case Report / Glomerulopatía 'full house' en un paciente con síndrome de lentigos múltiples: un reporte de caso

ABSTRACT Multiple lentigines syndrome (MLS) is an autosomal dominant disease which is usually diagnosed clinically by the presence of characteristic features. The molecular genetic testing is an adjuvant diagnostic tool to identify the mutation of particular genes such as PTPN11 genes, RAF1, BRAF or MAP2K1 genes. This syndrome was formerly known as LEOPARD syndrome or Noonan syndrome with multiple lentigines. 'LEOPARD syndrome ' is an acronym of characteristic features (Lentigines, Electrocardiographic conduction abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormalities of the genitalia, Retardation of growth, and Deafness). There was no previous case report about any glomerulonephropathy in association with MLS. We present a case of a patient with MLS with recurrent nephrotic syndrome who was found to have histologic evidence of 'full house ' glomerulopathy.

RESUMEN El síndrome de lentigos múltiples (SLM) es una enfermedad autosómica dominante que de modo general se diagnostica clínicamente por la presencia de rasgos característicos. La prueba genética molecular es una herramienta de diagnóstico auxiliar utilizada para identificar la mutación de genes específicos tales como los genes PTPN11, RAF1, BRAF, o los genes MAP2K1. Este síndrome se conocía anteriormente como síndrome del leopardo o síndrome de Noonan con múltiples lentigos. El síndrome toma su nombre del acrónimo en inglés LEOPARD, que describe sus rasgos característicos (L lentigos; E conducción electrocardiográfica de las anormalidades; O hipertelorismo ocular; P estenosis pulmonar; A anormalidades de los genitales; R retardo del crecimiento; y D deafness, 'sordera ' en inglés), y que fuera introducido por Gorlin et al en 1969. No existía ningún reporte de caso anterior sobre glomerulonefropatía asociada con SLM. Presentamos el caso de un paciente con SLM con síndrome nefrótico recurrente en el que se halló evidencia histológica de glomerulopatía 'full house'.

A Rare Case of Left Ventricular Noncompaction in LEOPARD Syndrome

No abstract available.

Do you know this syndrome? Leopard syndrome

ABSTRACT Hypertrophic cardiomyopathy is known as Leopard syndrome, which is a mnemonic rule for multiple lentigines (L), electrocardiographic conduction abnormalities (E), ocular hypertelorism (O), pulmonary stenosis (P), abnormalities of genitalia (A), retardation of growth (R), and deafness (D). We report the case of a 12-year-old patient with some of the abovementioned characteristics: hypertelorism, macroglossia, lentigines, hypospadias, cryptorchidism, subaortic stenosis, growth retardation, and hearing impairment. Due to this set of symptoms, we diagnosed Leopard syndrome.

Síndromes lentiginosos familiares / Family lentiginous syndromes

Los síndromes lentiginosos familiares (SLF)involucran un amplio espectro fenotípico, que abarcadesde una predisposiciónhereditaria a desarrollar lentigos sinenfermedad sistémica hasta un riesgo incrementado en la formación de hamartomas, hiperplasias y otras neoplasias.El prototipo de SLF es el síndrome de Peutz-Jeghers, pero también se incluyen dentro de este grupo de patologías el complejo de Carney, el síndrome LEOPARD, el síndrome de Bannayan-Riley-Ruvalcaba, la enfermedad de Cowden, el síndrome de Laugier-Hunziker, la disección arterial con lentiginosis y las lentiginosis benignas (lentiginosis unilateral parcial y centrofacial).La presencia de lentigos es uno de los hallazgos semiológicos más prominentes en estos cuadros y probablemente, más que una característica clínica asociada, sea el reflejo de la convergencia entre vías de señalización de importancia crucial para la embriogénesis, la diferenciación de la cresta neural, el crecimiento de los órganos diana y el funcionamiento de una amplia gama de tejidos.En el presente trabajo se realiza una descripción detallada de cada uno de los SLF, incluyendo el mecanismo molecular involucrado, las manifestaciones clínicas, la metodología diagnóstica, el seguimiento y el tratamiento.

Familial lentiginosis syndromes involve a broad phenotypic spectrum that includesfrom hereditary predisposition to presentlentigines without systemic disease to the increased risk of hamartomas, hyperplasia and other malignancies development.The prototype is Peutz-Jeghers syndrome, but Carney complex, LEOPARD syndrome, Bannayan-Riley-Ruvalcaba syndrome, Cowden's disease, Laugier-Hunziker syndrome, arterial dissection with lentigines and benign lentiginosis (partial and unilateral centrofaciallentigines) are also included in this group.The presence of lentigines is the most relevant finding and probably more than a clinical feature associated represents a reflection of the convergence of crucial signaling pathways that are important to embryogenesis, differentiation of the neural crest, target organs growth and funcional of a wide range of tissues.In this paper we perform a detailed description of these syndromes, including the molecular mechanisms involved, clinical manifestationsdiagnostic procedures, monitoring, and treatment.

Síndrome de Leopard: relato de uma rara doença autossômica dominante / Leopard?s syndrome: report on a rare autosomic dominant disease

A síndrome de Leopard é uma rara doença autossômica dominante, causada por mutação em PTPN11. O nome da síndrome foi introduzido por Gorlin (1969), mas foi primeiramente descrita por Zeisle e Becker (1935). O nome da síndrome corresponde às iniciais das manifestações clínicas típicas: lentigos (L), defeitos de condução eletrocardiográficos (E), hipertelorismo ocular (O), estenose pulmonar (P), alterações genitais (A), retardo do crescimento (R) e "deafness" - surdez (D). Corresponde a uma doença dismorfogenética complexa de penetrância variável...

LEOPARD Syndrome with PTPN11 Gene Mutation / 대한피부과학회지

LEOPARD syndrome is an autosomal dominant inherited disease with multiple congenital anomalies. LEOPARD is an acronym for Lentigines, Electrocardiographic conduction defects, Ocular hypertelorism, Pulmonary stenosis, Abnormalities of the genitalia, Retardation of growth, and Deafness. The disorder is caused by mutations in the PTPN11 gene or RAF1 gene. Here we report two typical cases of LEOPARD syndrome with lentigines, electrocardiograph abnormality, ocular hypertelorism which were proven to be the results of genetic mutations. Moreover, one 12-year-old boy showed growth retardation, deficiency in testosterone; the other 5-year-old girl had undergone implantation of a cochlear device and was diagnosed as having hypertrophic cardiomyopathy which has been managed with a beta blocker. Each patient showed a PTPN11 gene mutation: Thr468Met in exon 12 and Tyr279Cys in exon 7, respectively.

Syndromic Hearing Loss in Association with PTPN11-Related Disorder: The Experience of Cochlear Implantation in a Child with LEOPARD Syndrome

Hearing loss (HL) is one of the most frequent clinical manifestations of patients who suffer with multi-systemic genetic disorders. HL in association with other physical stigmata is referred to as a syndromic form of HL. LEOPARD syndrome (LS) is one of the disorders with syndromic HL and it is caused by a mutation in the PTPN11 or RAF1 gene. In general, 5 year old children who undergo cochlear implantation usually show a marked change in behavior regarding sound detection within the first 6 months of implant use, but word identification may not be exhibited for at least another 6-12 months of implant use. We herein report on a 5-year-old girl with LS. Her clinical manifestations including bilateral sensorineural HL, which indicated the diagnosis of LS. We confirmed the diagnosis by identifying a disease-causing mutation in the PTPN11 gene, which was a heterozygous missense mutation Ala461Thr (c.1381G>A). She underwent cochlear implantation (CI) without complications and she is currently on regular follow-up at postoperative 1 year. This is the first reported case of CI in a patient with LS in the medical literature.

Síndrome LEOPARD: comunicación de cuatro casos y revisión de la literatura / LEOPARD syndrome: Report of four cases and review of the literature

El síndrome de lentiginosis múltiple o síndrome LEOPARD es una genodermatosis rara de herencia autosómica dominante. Presenta múltiples anomalías congénitas y un importante compromiso cutáneo, por lo que el dermatólogo tiene un rol primordial en el diagnóstico. El acrónimo indica las principales manifestaciones del síndrome: Lentiginosis, alteraciones Electrocardiográficas, hipertelorismo Ocular, estenosis Pulmonar, Anomalías genitales, Retraso del crecimiento y sordera (Deafness). En el 90% de los pacientes se encuentra una mutación del gen PTPN11, el cual codifica una proteína tirosina fosfatasa que controla distintos procesos del desarrollo así como diferentes funciones celulares. Es fundamental el diagnóstico temprano de esta entidad, ya que facilita la prevención y/o el control de las complicaciones (principalmente de las manifestaciones cardíacas, que son las que afectan la vida del paciente) y permite, además, realizar el asesoramiento genético. Describimos cuatro casos familiares de síndrome LEOPARD en los que se arribó al diagnóstico a partir de llentiginosis.Multiple lentigines syndrome or LEOPARD.

Syndrome is a rare genodermatosis of autosomal dominant inheritance characterized by multiple congenital anomalies and important involvement of the skin, giving a basic the dermatologist a key role in the diagnosis. The acronym indicates the main features of the syndrome: Lentigines, Electrocardiographics alterations, Ocular hypertelorism, Pulmonar stenosis, genital Anomalies, Retard of growth and Deafness. Ninety percent of patients show a mutation of the PTPN11 gene that encodes a tyrosine phosphatase protein, which controls different processes of development, as well as different cellular functions. Early diagnosis is crucial, as it allows the prevention and/or control of complications, mainly the cardiac manifestations which are the ones that may threaten the patient’s life. In addition, it allows genetic counseling. We describe four cases of LEOPARD.

LEOPARD Syndrome with PTPN11 Gene Mutation Showing Six Cardinal Symptoms of LEOPARD

LEOPARD multiple congenital anomaly syndrome inherited in an autosomal dominant manner. LEOPARD is an acronym for Lentigines, Eletrocardiographic conduction defects, Ocular hypertelorism, Pulmonary valve stenosis, Abnormalities of the genitalia, Retardation of growth, and Deafness. Clinical diagnosis is primarily based on multiple lentigines, typical facial features, and the presence of hypertrophic cardiomyopathy and/or cafe-au-lait macules. We report a typical case of LEOPARD syndrome with PTPN11 gene mutation associated with lentigines, electrocardiograph abnormality, ocular hypertelorism, pulmonary valve stenosis, growth retardation, and sensorineural hearing loss.

The Management of Cardiovascular Abnormalities in Patient With LEOPARD Syndrome

LEOPARD syndrome (LS) is a rare hereditary disorder in Asian countries. This syndrome consists of multiple systemic abnormalities. In particular, characteristic cardiovascular effects in LS may include variable clinical manifestations from benign to life-threatening courses. The cardiac effects of this syndrome consist of left ventricular hypertrophy (LVH), pulmonary stenosis (PS), coronary artery dilatation and electrocardiogram(ECG) abnormalities. Since there are few LS patients who have undergone a complete cardiovascular evaluation, the nature and clinical prognosis of cardiovascular abnormalities in this syndrome remain uncertain. Also, there have been few reports on therapeutic strategies for cardiovascular abnormalities in LS. Here we describe a case of LS who presented with multiple cardiovascular problems and underwent successful surgical and medical treatment.

Síndrome Leopard e miocardiopatia hipertrófica: uma associação relacionada à morte súbita / Síndrome leopard y miocardiopatía hipertrófica: una asociación relacionada a la muerte súbita / Leopard syndrome and hypertrophic cardiomyopathy: an association related to sudden death

Relatamos a rara associação entre síndrome Leopard e miocardiopatia hipertrófica em mulher de 27 anos, pouco sintomática, que veio para estratificação e prevenção de risco de morte súbita. Portadora de uma síndrome rara, que se manifesta com pequenas máculas disseminadas pelo corpo, além de alterações oculares, genitais, cardíacas e de crescimento. A associação de miocardiopatia hipertrófica com fatores de risco de morte súbita determinou a indicação do implante de cardiodesfibrilador (CDI) para prevenção primária.

We describe an uncommon association between Leopard syndrome and hypertrophic cardiomyopathy in a 27-year-old woman, who was little symptomatic and came for sudden death risk stratification and prevention. She has a rare syndrome, whose symptoms are maculae over the body and abnormalities in eyes, genital organs, heart and in growth. Association of hypertrophic cardiomyopathy with sudden death risk factors determined the implantation of cardioverter-defibrillator (ICD) for primary prevention.

Relatamos la rara asociación entre síndrome Leopard y miocardiopatía hipertrófica en una mujer de 27 años, poco sintomática, que vino para estratificación y prevención de riesgo de muerte súbita. Portadora de un síndrome raro, que se manifiesta con pequeñas manchas diseminadas por el cuerpo, además de alteraciones oculares, genitales, cardíacas y de crecimiento. La asociación de miocardiopatía hipertrófica con factores de riesgo de muerte súbita determinó la indicación del implante de cardiodesfibrilador (CDI) para prevención primaria.

Sindrome LEOPARD: a propósito de la mancha café negro / LEOPARD syndrome: speaking of black coffee stain

El síndome LEOPARD constituye una genodermatosis autosómica dominante, con expresividad variable. La lentiginosidad y las anomalías cardíacas constituyen las manifestaciones clínicas más frecuentes. Se ha descrito la presencia de “manchas café negro” con hallazgos histopatológicos dispares. En nuestra paciente el estudio de la misma fue vinculable a un nevo pigmentario (mancha café con leche).

Síndrome de Leopard: comunicación de un caso, asociación de lentiginosis, hipoacusia y cardiopatía / Leopard syndrome: case presentation, association of lentiginosis, hypoacusia and cardiopathy

Paciente de 33 años de sexo masculino que fue evaluado en nuestro hospital con diagnóstico presuntivo de síndrome de Leopard; en él hallamos lentiginosis múltiple presente desde el nacimiento con exacerbación en la adolescencia distribuida en cara, tronco y miembro, miocardiopatía hipertrófica, hipertelorismo e hipoacusia perceptiva. Se trata de una patología de escasa prevalencia, de origen genético y transmisión autosómica dominante, que combina el hallazgo dermatológico con patología cardiovascular que puede incluir estenosis de válvula pulmonar ó aórtica, hipoacusia, alteraciones genitales y patologías musculoesqueléticas. El hallazgo de este patrón sindrómico debe guiar al médico hacia la pesquisa de las anomalías asociadas, ya que algunas pueden tener implicaciones pronósticas

Estudo do gene PTPN11 nos pacientes afetados pela síndrome de Noonan / The PTPN11 gene analysis in Noonan syndrome patients

A análise do gene PTPN11 foi realizada em 50 probandos com síndrome de Noonan e 8 com síndrome de Noonan-like. Na síndrome de Noonan foram identificadas mutações missense em 42 por cento dos afetados, corroborando a heterogeneidade genética desta doença. A mutação T73I parece predispor a uma doença mieloproliferativa na síndrome de Noonan, embora uma correlação genótipo-fenótipo ainda não tenha sido estabelecida. O gene PTPN11 é o principal responsável pela síndrome de LEOPARD (3/3 pacientes com mutação) e, em parte, pelas síndromes da neurofibromatose-Noonan (1 com mutação) e Noonan-like/lesões múlitplas de células gigantes (1/3 com mutação) / A PTPN11 gene analysis was performed in 50 Noonan and 8 Noonan-like syndrome probands. Missense mutations were identified in 42 per cent of the Noonan syndrome cohort, corroborating the idea of its genetic heterogeneity. A definitive genotype-phenotype correlation was not established, but the T73I mutation seems to predispose to a myeloproliferative disorder in Noonan syndrome. The PTPN11 gene is the main one in LEOPARD syndrome (3/3 patients with the same mutation) and it plays a role in neurofibromatosis-Noonan (one patient had a PTPN11 gene mutation) and Noonan-like/multiple giant cell lesion syndromes (1/3 with a PTPN11 gene mutation)...

A Case of LEOPARD Syndrome / 대한피부과학회지

LEOPARD syndrome is an autosomal dominantly inherited multiple congenital anomaly syndrome with high penetrance and a markedly variable expression. LEOPARD is an acronym of lentigines, electrocardiographic conduction defects, ocular hypertelorism, pulmonary stenosis, abnormalities of the genitalia, retardation of growth, and deafness. We report a typical case of LEOPARD syndrome which developed in an 11-year-old girl who had symptoms of lentigines, EKG abnormality, ocular hypertelorism, pulmonary stenosis, growth retardation, and sensorineural hearing loss.

A Case of Multiple Lentigines Sydrome with a Family History of Multiple Lentigines / 대한피부과학회지

Multiple lentigines syndrome is an autosomal dominant disorder of variable penetrance and expressivity. LEOPARD has been used to describe the main features of the syndrome, including lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of growth and deafness. We describe a case of multiple lentigines syndrome with a family history of multiple lentigines. A 15-year-old boy presented with multiple brown macules and patches on the whole body, which had developed since the age of 3. He also had hypertrophic cardiomyopathy, EKG abnormalities and retarded growth. His maternal grandfather, maternal uncle and mother also presented with multiple brown macules scattered over the body. The biopsy specimen taken from the macule revealed elongated rete ridges, increased melanin deposition and increased number of melanocytes.

A case of LEOPARD syndrome with cor triatriatum / 대한내과학회지

The LEOPARD syndrome is an acronym and serves as a mnemonic for the features of this autosomal dominant syndrome : L - lentigines (multiple), E - electrocardiographic conduction abnormalities, O - ocular hypertelorism, P - pulmonary stenosis, A - abnormalities of genitalia, R - retardation of growth, and D - deafness (sensoryneural). The main features of the syndrome are multiple lentigines in combination with congenital heart malformations. These frequently accompanied cardiac abnormalities are pulmonary stenosis, hypertrophic cardiomyopathy, and various ECG abnormalities. It is advisable to make cardiac evaluation in a patient with LEOPARD syndrome in spite of no clinical symptoms or signs, since cardiac dysfunction may be progressive or developed later. We experienced a case of this syndrome in a 31 year-old female, presenting multiple lentigines, ocular hypertelorism, and congenital cardiac abnormalities of incomplete right bundle branch block and cor triatriatum. We report the case with brief literature review.

A Case of Leopard Syndrome with Atypical Psychosis / 신경정신의학

Leopard syndrome is a neurocutaneous syndrome which may affect a variety of organ systems in the embryological aspects. It presents lentigines, EKG abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of growth, and deafness as major teatures.We report a case of Leopard Syndrome with atypical psychotic features. The patient had many lentigenies on the face, cafe au lait spots on the part of the waist and the buttocks, mild atrial regugitation, clinodactyly, hyperextensibility of distal interphalangeal joint, flat foots, subclinical hypothyrodism, sensorineural deafness, and mild mental retardation. He also had autistic disorder, compulsion, pathologic collection, and violent behaviors as psychiatric problems. This raises a possibility that psychiatric diseases may be related to the variation of neuroectoderm. In clinical practice, when psychopathic patients with specific skin lesions are seen for consultation, the consideration of embryologically common aspects of both disease groups can be helpful to the discovery of abnormalities in other organs and to its treatment.