Gene mutation analysis of a family with familial generalized lentiginosis / 中华皮肤科杂志

Objective:To analyze clinical and genetic characteristics of a family with familial generalized lentiginosis, and to identify the causative gene mutation.Methods:Clinical characteristics and inherited pattern were analyzed in a family with familial generalized lentiginosis. Peripheral blood samples were obtained from the proband, his affected father and healthy mother, and genomic DNA was extracted. PCR was performed to amplify all exons and their flanking sequences of the SASH1 gene, followed by DNA sequencing. The proband′s mother and 100 unrelated healthy controls served as controls to determine the mutation site. Previous literature and gene mutation databases were searched to rule out the possibility that the SASH1 gene mutations were single nucleotide polymorphisms, and to determine whether it was a known mutation.Results:A 4-generation family consisting of 17 members was investigated, and there were 9 patients in the family, including 7 males and 2 females. Patients existed in each generation, and the disease was inherited in an autosomal dominant manner in this family. Gene sequencing revealed a heterozygous duplication mutation c.49_54dupCCCGAG in exon 1 of the SASH1 gene in the proband and his father. This mutation was not found in his mother or healthy controls, and had not been reported in previous literature or gene mutation databases.Conclusion:The heterozygous duplication mutation c.49_54dupCCCGAG in the SASH1 gene is a pathogenic mutation for the clinical manifestations of familial generalized lentiginosis in this family.

Síndrome de Bannayan-Riley-Rubalcaba en pediatría / Bannayan-Riley-Rubalcaba syndrome in pediatrics

Resumen Introducción: El síndrome de Bannayan-Riley-Ruvalcaba (SBRR) forma parte de la enfermedad de PTEN tumor-hamartoma, que comprende los síndromes de Cowden, Proteus y similar a Proteus, los cuales presentan un espectro de lesiones cutáneas, mucosas, de mama, tiroides y tracto gastrointestinal, así como polipomatosis hereditaria autosómica dominante. El SBRR se caracteriza por macrocefalia, lipomatosis, hemangiomatosis, pólipos intestinales, lentiginosis genital y discapacidad intelectual. El diagnóstico clínico y de variantes patogénicas en el gen PTEN, detectables en el 60% de los afectados, brinda la oportunidad de un manejo adecuado y de asesoramiento genético. Caso clínico: Se reporta el caso de un paciente en edad escolar que fue enviado a valoración inicial a dermatología por presentar antecedente de macrocefalia al nacimiento, lentiginosis genital, retraso en el desarrollo psicomotor y posteriormente rectorragia secundaria a polipomatosis intestinal. Se le realizó el diagnóstico clínico y molecular de SBRR. Conclusiones: El SBRR es poco frecuente, lo que puede retrasar el diagnóstico para los pacientes y los familiares en riesgo, por lo que es importante conocer sus características clínicas en el paciente pediátrico para lograr un diagnóstico y un manejo oportunos.

Abstract Background: Bannayan-Riley-Ruvalcaba syndrome (BRRS) is part of the PTEN tumor-hamartoma disease, which includes the Cowden, Proteus and Proteus-like syndromes, which present a spectrum of skin, mucosal, breast, thyroid, and gastrointestinal tract lesions, as well as autosomal dominant hereditary polypomatosis. BRRS is characterized by macrocephaly, lipomatosis, hemangiomatosis, intestinal polyps, genital lentiginosis, and intellectual disability. Clinical diagnosis and diagnosis of pathogenic variants in the PTEN gene, detectable in 60% of those affected, provides the opportunity for appropriate management and genetic counseling. Case report: We report the case of a school-age patient who was sent to an initial dermatological evaluation for presenting a history of macrocephaly at birth, genital lentiginosis, delayed psychomotor development and later rectal bleeding secondary to intestinal polypomatosis. A clinical and molecular diagnosis of BRRS was carried out. Conclusions: BRRS is rare, which can delay the diagnosis for patients and relatives at risk, so it is important to know its clinical characteristics in pediatric patients to achieve a timely diagnosis and management.

Bilateral Segmental Neurofibromatosis with Lentiginosis Showing a Checkerboard Pattern / 대한피부과학회지

Segmental neurofibromatosis, a subtype of neurofibromatosis type 1, is characterized by neurofibromas and/or café-au-lait spots limited to an area or segment of the body. Checkerboard pattern is a rare type of cutaneous mosaic manifestation, characterized by squares or broad ribbons of affected skin with sharp demarcation at the midline. Herein, we report the case of a patient with bilateral segmental neurofibromatosis with lentiginosis showing a checkerboard pattern. Our patient had multiple hyperpigmented macules on her entire body in a checkerboard pattern since birth. Several café-au-lait patches were observed on the left buttock and right axilla. A neurofibroma was incidentally found beneath the café-au-lait patch by histological examination, which showed ill-defined spindle cells with elongated nuclei at the deep dermis that stained positive for S-100. Based on the clinical presentation and histopathologic results, the patient was diagnosed with bilateral segmental neurofibromatosis with lentiginosis showing a checkerboard pattern.

Síndrome de Laugier-Hunziker / Laugier-Hunziker syndrome

El síndrome de Laugier-Hunziker es un trastorno pigmentario adquirido poco frecuente, caracterizado por presentar lesiones hiperpigmentadas cutaneomucosas idiopáticas que pueden asociarse a melanoniquia longitudinal. A pesar de ser considerado una enfermedad benigna sin manifestaciones sistémicas ni potencial maligno, es clave realizar el diagnóstico diferencial con otros trastornos pigmentarios, en especial con el síndrome de Peutz-Jeghers. Se presenta aquí el caso de un paciente con este síndrome poco frecuente. (AU)

Laugier-Hunziker syndrome is a rare acquired pigmentary disorder that is characterized by idiopathic mucocutaneous pigmentation that may be associated with longitudinal melanonychia. Although this syndrome is considered a benign disease with no systemic manifestations or malignant potential, it is important to rule out other mucocutaneous pigmentary disorders, especially Peutz-Jeghers syndrome. We report the case of a patient with this unusual syndrome. (AU)

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.

Partial Unilateral Lentiginosis with an Ocular Involvement / 대한피부과학회지

Partial unilateral lentiginosis is a rare pigmentary disorder which is characterized by multiple grouped lentigines in unilateral or segmental distributions. The ocular involvement of the disease is extremely rare and only four cases have been reported until today. The exact pathophysiology is still unknown. An 18-year-old woman is being presented with unilateral hyperpigmented macules on her left forehead, eyelid, cheek, lip and chin which all demarcated sharply at the midline of her face. The lesion has been presented since the age of 1. Also, there are discrete brownish pigmentations on her left bulbar conjunctiva. Biopsy specimen is being obtained from the left chin and the histopathological examinations revealed increasing basal layer of pigmentations and mild elongation of rete ridges. The histopathological features are also consistent with lentigo simplex. Herein, we present a rare case of partial unilateral lentiginosis with an ocular involvement. We have also proposed that the partial unilateral lentiginosis has a possibility of ocular involvements.

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.

Lentiginosis unilateral parcial / Unilateral partial lentiginosis

La lentiginosis unilateral parcial (LUP) es un raro desorden pigmentario caracterizado por numerosos lentigos, dispuestos en grupo, que se presentan durante la infancia, asintomáticos, y comprometen de manera unilateral un segmento del cuerpo: cabeza, cuello, tronco, extremidades, etc. Pocas veces sobrepasan la línea media, permaneciendo estables en el tiempo. Presentamos cinco casos clínicos y una breve revisión del tema...

Partial Unilateral Lentiginosis (PUL) is a rare pigmentarydisorder characterized by numerous asymptomatic andstable lentigines confined to one side of the body.It begins in childhood, affecting different body segmentsincluding the head, neck, trunk and extremities.Lentigines rarely surpass the midline.We present five cases and briefly review the subject...

Agminated Lentiginosis with a Family History / 대한피부과학회지

Agminated lentiginosis (AL) is a rare pigmented disorder that is characterized by numerous lentigines in a unilateral distribution or often in a segmental pattern corresponding to one or more dermatomes. AL coexists with other several diseases and some researchers have suggested it is a variant of dermatomal neurofibromatosis if AL is accompanied by cafe-au-lait (CAL) macules or neurofibromas. We report here on a case of a 12-year-old female who presented with multiple lentigines on her right neck and shoulder (the C2 and C3 dermatomes) combined with CAL macule and ipsilateral axillary freckling. On checking the family history, her mother had grouped lentigines on her right chest (the T4, T5 dermatomes). But there were no neurofibromas, Lisch nodules and neurologic or skeletal abnormalities in both of them.

Síndrome de Peutz-Jeghers y Obstrucción Intestinal Baja, Reporte de un Caso / Peutz-Jeghers Syndrome and Low Intestinal Obstruction, Report of a Case

El presentamos el caso clínico de un niño de 12 años, que acude al Servicio de Pediatría del Hospital Manuel Ascencio Villarroel, transferido del Centro Pediátrico Albina Rodríguez de Patiño con los posibles diagnósticos de estreñimiento pertinaz, desnutrición de III grado secundario, Síndrome de Peutz-Jeghers probable, anemia microcítica e hipocrómica severa y soplo sistólico en estudio. Si bien el Síndrome de Peutz-Jeghers se presenta en contadas ocasiones en nuestro medio, el diagnóstico diferencial y sus complicaciones deben ser mejor estudiadas para así poder ser tratada de forma más oportuna. Consideramos importante este reporte porque en nuestro medio es una rara causa de abdomen agudo.

The present case report of a child 12 year old boy, who was admitted to the pediatric department of the Hospital Manuel AscencioVillarroel, transferred to the Pediatric Center Albina Rodriguez Patiño with possible diagnoses of persistent constipation, grade III secondary malnutrition, Peutz-Jeghers probable syndrome, severe hypochromic microcytic anemia and systolic murmur in the study.While the Peutz-Jeghers syndrome rarely occurs in our environment, the differential diagnosis and its complications should be better studied so we can be treated in a more timely manner. We consider it important our report because this disease is a rare cause of acute abdomen in our environment.

A Case of Partial Unilateral Lentiginosis with Cafe-au-lait Macules / 대한피부과학회지

Partial unilateral lentiginosis (PUL) is an unusual pigmentary disorder that's characterized by multiple lentigines in a unilateral distribution. The lesions often have a segmental pattern with a sharp demarcation at the midline. This is sometimes combined with other disorders such as neurofibromatosis or cafe-au-lait macules (CALMs). The presence of multiple CALMs in the same distribution as the lentigines on a PUL patient makes it difficult to differentiate PUL from segmental neurofibromatosis. We present here a 25-year-old woman with an unusual combination of several caf?-au-lait macules and scattered numerous lentigines involving the left side of the abdomen, flank and back.

Bilateral Segmental Neurofibromatosis with Partial Unilateral Lentiginosis: Case Report with Review of the Literature

Bilateral segmental neurofibromatosis is a rare disease characterized by bilateral neurofibromas, with or without pigmented lesion, or unilateral neurofibromas with contralateral pigmented lesion, limited to a body segment. Partial unilateral lentiginosis is characterized by numerous lentigines localized to a body segment, often corresponding to one or more dermatome. Bilateral segmental neurofibromatosis combined with partial unilateral lentiginosis is very rare, and to our knowledge, only 2 cases have been reported in English literature. We herein report another case of bilateral segmental neurofibromatosis with partial unilateral lentiginosis in a 46-year-old woman.

A Case of Bilateral Segmental Neurofibromatosis Associated with Partial Unilateral Lentiginosis and Nevus of Ota / 대한피부과학회지

The term, bilateral segmental neurofibromatosis had been used to refer to patients who had unilateral neurofibromas with contralateral pigmented lesions or bilateral neurofibromas. Partial unilateral lentiginosis is characterized by numerous lentigines localized to a body segment. The coexistence of bilateral neurofibromas and partial unilateral lentiginosis raises the possibility that partial unilateral lentiginosis could be a variant of segmental neurofibromatosis. Nevus of Ota arise from dermal melanocytes and it can be associated with neurofibromatosis. A 60-year-old man presented with bilateral segmental neurofibromatosis with partial unilateral lentiginosis on the right arm and right leg, nevus of Ota on right forehead, and one cafe-au-lait spot on the abdomen.

A Case of Partial Unilateral Lentiginosis with Familial History / 대한피부과학회지

Partial unilateral lentiginosis is a rare pigmentary disorder characterized by the numerous unilateral lentigines on the otherwise normal skin. A 13-year-old woman presented with asymptomatic multiple brownish macules on the left periorbital area. Her mother and maternal grandfather had the same clinical features on the left abdomen. Histologic examination of the pigmented lesion revealed findings consistent with lentigo simplex. We report an interesting case of partial unilateral lentiginosis with familial occurrence.

Partial Unilateral Lentiginosis:Clinicopathologic Review of 13 Cases

BACKGROUND: Partial unilateral lentiginosis (PUL) is a rare pigmentary disorder characterized by grouped multiple lentigines on otherwise normal skin that histologically have the typical features of lentigo. This entity has been only rarely reported in the Korean population. OBJECTIVE: The purpose of this study was to evaluate clinical and histopathologic characteristics, association with other disorders, and differential diagnosis of PUL. METHODS: We reviewed our experiences of thirteen cases of PUL which had been collected in our dermatology clinic during the 6-year period between 1993 and 1998. RESULTS: Twelve patients were female and one was male. In 3 patients the lesions appeared after the age of 20 years. Ten patients had the lesions on the upper part of the body, the neck being the most common location. No bias was shown in terms of the side of the body affected. Cafe-au-lait macules (one to three) were found in six patients, axillary freckles were observed in two. Histopathologic examination of biopsy specimens commonly showed hyperpigmentation of the basal layer, elongation of rete ridges, and an increased number of melanocytes. There ,was no evidence of associated disorders or family history. CONCLUSION: Based on this data, we confirmed that PUL is a benign, idiopathic lentiginosis with no commonly associated abnormalities. Furthermore, we believed that PUL is not uncommon in Korean people.

Partial Unilateral Lentiginosis

Partial Unilateral Lentiginosis (PUL) is a rare pigmentary disorder characterized by the numerous lentigines confined to a body segment, with a sharp demarcation at the midline. We report two cases of PUL. A 38-year-old woman had asymptomatic discrete small hyperpigmented macules that were scattered on the T7~L1 dermatomes on the left side of her trunk and were clearly demarcated in the midline on both anterior and posterior sides. In the other case, an 18- year-old woman had hyperpigmented macules that were scattered on the left neck, shoulder, and anterior chest. Other anomalies including neurofibromatosis, neurologic anomalies, and multiple lentiginous syndrome were not related in both cases. We report two cases of PUL having no other anomalies.

Two Cases of Partial Unilateral Lentiginosis / 대한피부과학회지

Partial unilateral lentiginosis(PUL) is a rare pigmentary disorder charaeterized by lentigines limited to one side of the body with or without neurologic abnormalities. We report two cases of PUL unassociated with any other defect, One patient was 20-year-old female who had lentigines confined to the right side of the face and the other was 19-year-old male who had lentigines confined to the left side of the neck and upper trunk and left upper extremity. Histologic examination of the pigmented lesion revealed findings consistent with lentigo simplex.