Síndromes neurocutáneos y leucemia linfoide aguda: a propósito de un caso / Neurocutaneous syndromes and acute lymphoid leukemia: a case report

Introducción: Los síndromes neurocutáneos comprenden un grupo heterogéneo de trastornos hereditarios que comprometen principalmente la piel y el sistema nervioso central. Dentro de estos se incluye la neurofibromatosis, la esclerosis tuberosa y la enfermedad de Von-Hippel Lindau. Se caracterizan por presencia de displasia en distintos tejidos y formación de tumores en diversos órganos. Se ha descrito también un riesgo relativo aumentado para leucemia linfoblástica aguda, leucemia mielomonocítica crónica y linfoma no Hodgkin. Objetivo: Describir caso de paciente con diagnóstico de síndrome neurocutáneo (esclerosis tuberosa) que desarrolló a los 6 años una leucemia linfoide aguda. Caso clínico: Paciente femenina, seis años de edad, con antecedentes de síndrome neurocutáneo tipo esclerosis tuberosa diagnosticado a los dos años de edad- Comenzó con síndrome febril, adenopatías cervicales y hepatoesplenomegalia. El hemograma mostró anemia, trombocitopenia grave y leucocitosis con presencia de blastos. En el medulograma se observó una infiltración de 90 por ciento de blastos linfoides, por lo que se diagnosticó como una leucemia linfoide aguda. Conclusiones: La coexistencia de síndromes neurocutáneos y leucemia linfoide aguda no es frecuente. Se describe una paciente con ambas enfermedades, que fallece a pesar del tratamiento(AU)

Introduction: Neurocutaneous syndromes comprise a heterogeneous set of hereditary disorders mainly affecting the skin and the central nervous system. Among the conditions included are neurofibromatosis, tuberous sclerosis and von Hippel-Lindau disease, characterized by dysplasia in various tissues and the formation of tumors in various organs. Increased relative risk has also been described for acute lymphoblastic leukemia, chronic myelomonocytic leukemia and non-Hodgkin lymphoma. Objective: Describe the case of a patient diagnosed with neurocutaneous syndrome (tuberous sclerosis) who developed acute lymphoid leukemia at age six. Clinical case: A case is presented of a female six-year-old patient with a history of neurocutaneous syndrome, tuberous sclerosis type, diagnosed at age two. The patient started with febrile syndrome, cervical adenopathies and hepatosplenomegaly. The blood count revealed anemia, severe thrombocytopenia and leukocytosis with the presence of blasts, whereas the medullogram showed 90 percent infiltration by lymphoid blasts, leading to the diagnosis of acute lymphoid leukemia. Conclusions: Coexistence of neurocutaneous syndromes and acute lymphoid leukemia is not frequent. A case is described of a patient with both conditions who died despite the treatment indicated(AU)

Morning glory disc anomaly associated with large facial infantile hemangioma as the presenting signs of PHACE syndrome / Anomalia de Morning Glory associada à extenso hemangioma infantil como apresentação da Síndrome PHACE

ABSTRACT Infantile hemangioma, the most common benign tumor in infancy, is usually an isolated condition occurring in many different locations in the body. However, large infantile hemangioma may be associated with other systemic malformations, including central nervous system, cerebrovascular, cardiac, and ophthalmology abnormalities, a condition termed PHACE syndrome. In this paper, we describe a case of PHACE syndrome that was presented with the unique association of a large facial infantile hemangioma and morning glory anomaly.

RESUMO O hemangioma infantil é a causa mais comum de tumor benigno na infância e usualmente é uma condição isolada podendo ocorrer em diferentes regiões do corpo. No entanto, hemangiomas infantil extensos podem ser associados com outras malformações sistêmicas incluindo anomalias no sistema nervoso central, cerebrovasculares, cardíacas e oftalmológicas, uma condição denominada síndrome PHACE. Neste trabalho, descrevemos o caso de um paciente com síndrome PHACE que se apresentou com um extenso hemangioma facial e anomalia de "morning glory".

Neurofibromatosis tipo 2, entidad a tener presente durante la práctica clínica / Neurofibromatosis type 2, entity to have present during clinical practice

La neurofibromatosis tipo 2 es un trastorno poco frecuente, que pertenece al grupo de las neurofibromatosis, que se caracterizan por la mayor propensión al desarrollo de tumores. Se presenta con múltiples tumores no malignos del sistema nervioso, incluidos schwannomas, meningiomas, ependimomas y gliomas, siendo los schwannomas vestibulares bilaterales una característica clásica. La mayoría de los casos se diagnostican en la adultez, sin embargo, las características clínicas habitualmente están presentes durante muchos años antes del diagnóstico. Es importante un alto índice de sospecha y un adecuado examen cutáneo y neurológico, ya que es crítico para hacer un diagnóstico correcto y precoz, y así, realizar un tratamiento interdisciplinario adecuado, evitando posibles complicaciones como son la pérdida auditiva y el uso de ayudas técnicas.

Neurofibromatosis type 2 is a rare disorder, belonging to the group of neurofibromatosis, which are characterized by the propensity for tumor development. The usual presentation are multiple non-malignant tumors of the nervous system, including schwannomas, meningiomas, ependymomas, and gliomas, with bilateral vestibular schwannomas being a classic feature. Most cases are diagnosed in adulthood; however, the clinical features are usually present for many years before diagnosis. A high index of suspicion and an adequate skin and neurological examination are important, since it is critical to make a correct and early diagnosis, so an appropriate interdisciplinary treatment can be performed, avoiding possible complications such as hearing loss and use of technical aids.

Multiple cardiac rhabdomyomas in tuberous sclerosis complex: case report and review of the literature

Cardiac rhabdomyoma is a benign tumor which constitutes the most common cardiovascular feature of the tuberous sclerosis complex, a multisystem genetically determined neurocutaneous disorder. Cardiac rhabdomyomas can be detected in the prenatal ultrasound, are usually asymptomatic and spontaneously regress within the first three years of life. Less often, the tumors' size, number, and location can produce a mass effect that may lead to blood flow abnormalities or organ dysfunction (heart failure and arrhythmia). In this setting, severe morbidity, and eventually, a lethal outcome despite clinical and surgical treatment may ensue. We describe a fatal case of multiple cardiac rhabdomyomas in a newborn girl. One of the rhabdomyomas was large and unfavorably located, causing significant obstruction of the left ventricular outflow tract. The autopsy identified, in addition to cardiac rhabdomyomas, brain glioneuronal hamartomas (cortical tubers), subependymal nodules and subependymal giant cell tumors, characteristic of the tuberous sclerosis complex. The newborn's family was investigated for the presence of typical clinical symptoms of the complex and image findings showed significant phenotypical variations and a broad symptom spectrum among the family members. This interesting case underscores the variability of tuberous sclerosis complex and the importance of performing a comprehensive postmortem examination in the identification of the cause of death, especially in the setting of familial disease.

Caso Clínico: Linfangioleiomiomatosis en una Paciente Joven con Síndrome de Bourneville

INTRODUCCIÓN: El síndrome de Bourneville o esclerosis tuberosa es una alteración innata del desarrollo que se transmite de forma autosómica dominante, es causada por mutación en los genes TSC1 y TSC2. Se presenta en 1 de cada 6 000 habitantes; se considera una forma rara de facomatosis susceptible de originar tumores benignos en diversas zonas del cuerpo, entre los que se cita: angiomiolipomas renales, tumores del sistema nervioso, retina, corazón, piel y linfangioleiomiomatosis pulmonar; siendo la última una patología pulmonar quística, progresiva, que afecta a las mujeres en edad fértil y puede ser potencialmente mortal. CASO CLÍNICO: Se trata de una paciente de sexo femenino de 23 años de edad, mestiza, con antecedentes de esclerosis tuberosa, hipotiroidismo y nefrectomía izquierda por angiomiolipoma; que presentó un neumotórax espontáneo secundario a linfangioleiomiomatosis pulmonar. EVOLUCIÓN: En base a los antecedentes patológicos, cuadro clínico y estudios de imagen se diagnosticó de linfangioleiomiomatosis pulmonar. Se realizó una pleurodesis y se inició tratamiento con Sirolimus; la respuesta fue satisfactoria, se mantuvieron controles médicos periódicos evaluando la posibilidad de trasplante pulmonar a futuro. CONCLUSIÓN: El neumotórax espontáneo en una mujer joven con esclerosis tuberosa se asocia a linfangioleiomiomatosis pulmonar; en la actualidad esta patología es manejada con Sirolimus, los resultados han sido favorables en la función pulmonar y calidad de vida del paciente; el trasplante pulmonar sigue siendo el tratamiento de elección en la enfermedad avanzada.(au)

BACKGROUND: Bourneville syndrome or tuberous sclerosis is an innate development alteration transmitted by autosomal dominant inheritance. It is caused by TSC1 and TSC2 gene mutations and occurs in 1 of every 6 000 people. It is considered a rare form of phacomatosis that can cause multiple benign tumors including renal angiomyolipomas and tumors of the central nervous system, retina, heart and skin; pulmonary lymphangioleiomyomatosis can be part of the clinical presentation, affects women of childbearing age and can be life-threatening. CASE REPORT: 23 year-old female patient with history of tuberous sclerosis, hypothyroidism and left nephrectomy for angiomyolipoma, who presented a spontaneous pneumothorax secondary to pulmonary lymphangioleiomyomatosis. EVOLUTION: Based on the history, clinical picture and imaging studies; the diagnosis of pulmonary lymphangioleiomyomatosis was made. A pleurodesis was performed and a treatment with Sirolimus was started; the response was satisfactory, periodic controls were maintained evaluating the possibility of lung transplant in the future. CONCLUSION: Spontaneous pneumothorax in a young woman with tuberous sclerosis is associated with pulmonary lymphangioleiomyomatosis. Currently this pathology is managed with Sirolimus, the results have been favorable , improving pulmonary function and quality of life; lung transplantation remains the treatment of choice in advanced disease.(au)

Use of Topical Rapamycin as Maintenance Treatment after a Single Session of Fractionated CO₂ Laser Ablation: A Method to Enhance Percutaneous Drug Delivery

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder with an incidence of approximately 1 in 5,000 to 10,000 live births. TSC has various clinical manifestations such as multiple hamartomas in systemic organs, including the skin. Angiofibromas are the most common skin lesions in patients with TSC. Although benign, angiofibromas develop in childhood and puberty, and can be psychosocially disfiguring for patients. Skin lesions in TSC, specifically angiofibromas, have no significant risk of malignant transformation after puberty; thus, they require no treatment if not prominent. However, the presentation of TSC is important owing to its impact on patient cosmesis. Surgical treatment and laser therapy are the mainstream treatments for angiofibromas. Although the evidence is limited, topical mammalian target of rapamycin inhibitors such as sirolimus (rapamycin) are effective in facial angiofibroma treatment. We describe an adult patient with an angiofibroma who had an excellent response to treatment with topical rapamycin after a single session of carbon dioxide (CO₂) laser ablation. The patient showed no sign of relapse or recurring lesions for a year. CO₂ laser ablation may serve as a new paradigm of treatment for angiofibromas in TSC. Since the selection of laser devices can be limited for some institutions, we suggest a rather basic but highly effective approach for angiofibroma treatment that can be generally applied with the classic CO₂ device.

Hypomelanosis of Ito with Multiple Congenital Anomalies

Hypomelanosis of Ito (HI) is a neurocutaneous disorder, also known as incontinentia pigmenti achromians. HI has been associated with chromosomal abnormalities, especially mosaicism. Herein, we report a case of HI with multiple congenital anomalies. A 2-month-old girl presented with multiple linear and whorling hypopigmentation on the face, trunk, and both extremities and patch alopecia on the scalp. Moreover, she had conical teeth, aniridia of the both eyes, and multiple musculoskeletal problems, including syndactyly and coccyx deviation. Cytogenetic analysis on peripheral blood was normal 46, XX, and no mutation was found in IKBKG gene test.

PHACE syndrome: clinical manifestations, diagnostic criteria, and management

Abstract: Infantile hemangioma can be linked to other organ malformations. In 1996, PHACE syndrome was first defined as the association of large and segmental infantile hemangioma, usually on the face, head, or cervical region, with malformations of the posterior fossa of the brain, arterial anomalies of the central nervous system, coarctation of the aorta, cardiac defects, and ocular abnormalities. Over 300 cases of PHACE syndrome have been reported, and it is cconsidered one of the most common neurocutaneous vascular disorders in childhood. Knowledge of the features and locations of lesions that imply a greater risk of systemic involvement is crucial for the diagnosis and proper management of PHACE syndrome patients. This review highlights the diagnostic criteria for PHACE syndrome, the imaging workup for extracutaneous involvement, the treatment of infantile hemangioma, and the importance of a multidisciplinary approach in the management of these patients.

Ataxia, telangiectasia con inmunodeficiencia / Ataxia, telangiectasia with immunodeficiency

La ataxia-telangiectasia es un trastorno autosómico recesivo, caracterizado por la presencia de telangiectasias oculocutáneas, ataxia cerebelosa progresiva, inmunodeficiencia e infecciones recurrentes. Además, está relacionado con neoplasias del sistema retículo-endotelial y trastornos inmunológicos. El objetivo de la presentación es destacar el papel del dermatólogo en este tipo de trastornos neurocutáneos, así como la importancia del seguimiento a largo plazo.

Ataxia telangiectasia is an autosomal recessive disorder characterized by oculocutaneous telangiectasia, progressive cerebellar ataxia, immunodeficiency, and recurrent infections. Besides, it is related to reticuloendothelial system neoplasms and immune disorders. The aim of this presentation is to emphasize the role of the Dermatologist in this type of neurocutaneous disorders and the importance of long-term follow up.

Hidrocefalia Congénita: Síndrome de Gómez-López-Hernández, un síndrome subdiagnosticado. Caso clínico / Congenital Hydrocephalus: Gómez-López-Hernández syndrome. An underdiagnosed Syndrome. A clinical case

Resumen: Introducción: Las hidrocefalias son condiciones complejas influenciadas por factores genéticos y ambientales. Excluyendo las hidrocefalias adquiridas por infección o tumores encefálicos, las hidrocefalias congénitas de causa genética pueden ocurrir de forma aislada (hidrocefalia aislada, pura o no sindromática) o como componente de un síndrome genético definido (hidrocefalia sindromática). Objetivo: Presentar una hidrocefalia congénita sindromática con un diagnóstico co nocido, y realizar una revisión de la literatura. Caso clínico: Preescolar con diagnóstico prenatal de hidrocefalia y romboencefalosinapsis, cariotipo y estudio de TORCH normales. Al nacer se confirmaron los diagnósticos prenatales y se excluyó malformación del desarrollo cortical cerebral. En la primera semana de vida se realizó derivación ventrículo peritoneal. En una reevaluación a la edad de 4 años, la ausencia de reflejos corneales y alopecia parietal bilateral asociado a romboencefalosinapsis reunieron los criterios diagnósticos definitivos de una displasia cerebelo-trigémino dermal (Síndrome de Gómez, López-Hernández (SGLH)). Conclusiones: El SGLH es un síndro me neurocutáneo infrecuente, posiblemente una condición esporádica que está subdiagnostica da. Con las nuevas tecnologías imageneológicas y genéticas pre y post natales podemos acceder a un diagnóstico de precisión de las hidrocefalias de origen genético, en el cual la alta sospecha de equipos de especialistas clínicos es esencial. Sin el diagnóstico preciso no podemos acceder a un pronóstico a largo plazo, prevención de morbilidad agregada y un consejo genético adecuado, que son requeridos en la pediatría actual.

Abstract: Introduction: Hydrocephalus is defined as complex conditions influenced by genetic and environmental factors. Excluding hydrocephalus acquired from infection or brain tumors, congenital hydrocephalus with a genetic cause may occur isolated (hydrocephalus isolated, pure or non-syndromatic) or as a component of a genetic syndrome (syndromic hydrocephalus). Objective: To present a syndromic congenital hydrocephalus with a known diagnosis, in order to be considered in the study of this pathology and to perform a review of hydrocephaly with a genetic cause. Clinical case: Preschool with a prenatal diagnosis of hydrocephalus and rhombencephalosynapsis, karyotype and study of TORCH was normal. At the moment of birth, the prenatal diagnoses were confirmed and a malformation of cerebral cortical development was excluded. During the first week of life, perito neal ventricle shunt was performed. A reevaluation at age 4, the absence of corneal reflexes bilate ral parietal and congenital focal alopecia associated with rhombencephalosynapsis, meet definitive criteria for cerebello-trigeminal-dermal displasia or Gómez-López-Hernández syndrome (GLHS). Conclusions: GLHS is an uncommon neurocutaneous syndrome, possibly a sporadic condition that is underdiagnosed. Due to the new imaging and genetic technologies pre and post-natal, today it is possible to achieve a better and more accurate diagnosis of hydrocephalus with a genetic origin, in which the high suspicion of teams of clinical specialists is essential. Without accurate diagnosis, we can not access to a long-term prognosis, prevention of aggregate morbidity or an adequate genetic counseling, which are required in today's pediatrics.

Facomatosis pigmentovascular tipo cesioflammea: a propósito de un caso / Phakomatosis pigmentovascularis cesioflammea: a case report

La facomatosis pigmentovascular es un síndrome caracterizado por la coexistencia de malformación vascular capilar con una lesión pigmentada cutánea congénita (nevo epidérmico, nevo spilus o melanocitosis dérmica). Existen diversos grupos de facomatosis pigmentovascular que dependen del tipo de nevo asociado a la lesión vascular. Los pacientes pueden presentar solo la afección cutánea o tener manifestaciones sistémicas, entre ellas, traumatológicas, neurológicas y oftalmológicas. Se expone el caso de una niña de un año de edad, con antecedentes de glaucoma congénito. Además, presentaba parálisis facial, melanosis ocular bilateral, malformación vascular capilar en la hemicara al igual que en el hemicuerpo izquierdo y mancha mongólica aberrante en la región dorsal superior, la zona lumbosacra y ambos glúteos. Debido a las manifestaciones clínicas cutáneas, se diagnosticó facomatosis pigmentovascular y se solicitó una evaluación neurológica y traumatológica, además de continuar con controles oftalmológicos. Los estudios complementarios son importantes para detectar alteraciones extracutáneas, como se presentaron en esta paciente.

Phakomatosis pigmentovascularis (PPV) is a syndrome characterized by the association of a vascular nevus with a congenital pigmented lesion (epidermal nevus, nevus spilus, and dermal melanocytosis). There are different types of PPV according to the pigmentary nevus associated with the vascular malformation. Patients may present only the cutaneous condition or have systemic manifestations, among them, trauma, neurological and ophthalmological disorders. We report the case of a 1-year-old girl who had congenital glaucoma. On examination, we identified facial paralysis, bilateral ocular melanosis, segmental capillary vascular malformation on the face as on left trunk and extremities, and aberrant Mongolian spots on the upper back, lumbosacral area and buttocks. Due to clinical manifestation, the diagnosis of PPV was made. The patient was evaluated by Neurology, Traumatology and keeps on with ophthalmological controls. Complementary studies are important, to rule out extracutaneous manifestations in PPV.

Parry-Romberg Syndrome Augmented by Hyaluronic Acid Filler

Parry Romberg Syndrome (PRS), also known as idiopathic progressive hemifacial atrophy, is a rare neurocutaneous disorder characterized by loss of skin and subcutaneous fat of face, muscles, and bones causing unilateral atrophy. Most patients require only soft tissue augmentation although syndrome has varying grades of severity. In the majority of reported cases, it has been treated with surgical flap or autologous fat transplantation. However, these treatments need complicated surgical skills which take a lot of time and cost. Herein we report the first case of PRS augmented by hyaluronic acid (HA) filler in a 42-year-old female patient to suggest that HA filler could be a safe, simple, and even rational economic alternative to surgical treatment.

A Case Report of Precocious Puberty in Children Associated with Hypothalamic Hamartoma in Neurofibromatosis Type 1 / 대한소아신경학회지

Neurofibromatosis type 1 (NF1) is a common neurocutaneous syndrome that presents with multiple café-au-lait spots, skinfold freckling, dermatofibromas, neurofibromas, and Lisch nodules. Mutations of the NF1 gene, encoding the protein neurofibromin, have been identified as the cause of this disease. NF1 can also present with precocious puberty and be associated with optic pathway tumors. Hypothalamic hamartoma as the cause of precocious puberty in patients with NF1 has been rarely described in the literature. Here, we report the findings for a patient with NF1 and precocious puberty associated with a hypothalamic hamartoma who had a newly discovered 14-bp deletion mutation in exon 5 of NF1. To our knowledge, this is the first time this combination is reported in the literature.

A Novel c.6766_6767insAA Mutation in the Neurofibromin Gene in a Patient with Neurofibromatosis Type 1-Associated Glioblastoma / 대한소아신경학회지

Neurofibromatosis type 1 (NF-1) is an autosomal dominant neurocutaneous syndrome caused by mutations in the neurofibromin gene. NF-1 patients have a high risk of tumors, and optic glioma is the most commonly observed central nervous system tumor in these patients. However, glioblastoma is extremely rare in pediatric NF-1 patients. Here we report the discovery of a novel heterozygous c.6766_6767insAA (p.Ser2256Lysfs*4), pathogenic mutation in the neurofibromin gene in a 17-year-old boy with NF-1-associated glioblastoma.

Forehead reconstruction with a custom-made three-dimensional titanium implant in a Parry-Romberg syndrome patient

Parry-Romberg syndrome is a rare neurocutaneous syndrome characterized by progressive shrinkage and degeneration of the tissues usually on only one side of the face. It is usually difficult to restore the facial contour due to skin tightness. In this case report, we report a forehead reconstruction with custom-made three-dimensional (3D) titanium implant of a Parry-Romberg syndrome patient who was treated with multiple fat grafts but had limited effect. A 36-year-old man presented with hemifacial atrophy. The disease progressed from 5 to 16 years old. The patient had alopecia on frontal scalp and received a surgery using tissue expander. The alopecia lesion was covered by expanded scalp flap done 22 years ago. Also, he was treated with fat grafts on depressed forehead 17 years ago. However, it did not work sufficiently, and there was noted depressed forehead. We planned to make 3D titanium implant to cover the depressed area (from the superior orbital rim to the vertex). During the operation, we confirmed that the custom-made 3D implant accurately fit for the depressed area without any dead spaces. Previously depressed forehead and glabella were elevated, and the forehead contour was improved cosmetically. A custom-made 3D titanium implant is widely used for skull reconstruction and bring good results. In our case, the depressed forehead of a Parry-Romberg syndrome patient was improved by a 3D titanium implant.

Sturge-Weber Syndrome in a 23-year old Nigerian male: A case report

Sturge-Weber syndrome (SWS, also called encephalofacial or encephalotrigeminal angiomatosis) is a neurocutaneous syndrome, characterized by the association of facial port-wine hemangiomas in the trigeminal nerve distribution area, with a vascular malformation of the brain (leptomeningeal angioma) with or without glaucoma. Herein, we reported Sturge-Weber syndrome in a 23-year-old man, who presented wi-th a right portwine hemangiomas, ipsilateral iris hyperchromia, suspected choroidalhaemangioma and glaucoma

A Case of Phacomatosis Pigmentovascularis Type IIa in a Korean Infant

No abstract available.

Tuberous Sclerosis Presenting with Connective Tissue Nevi Only: Usefulness of Genetic Testing / 대한피부과학회지

Tuberous sclerosis complex (TSC) is a neurocutaneous disorder with variable manifestations. The diagnosis is based on clinical criteria, and is divided into definite, probable, and possible TSC. If patients present with mild symptoms, clinicians may hesitate to perform further evaluations because of the high economic burden. A 16-year-old male presented with multiple skin-colored papules on the lower back and buttock. The histopathologic findings were compatible with connective tissue nevi (CTN). No other findings were observed with the exception of one hypomelanotic macule on the left shin. As the patient's parents wished to confirm the diagnosis, genetic testing was performed, and a TSC1 gene mutation was detected. With this genetic result, further evaluations were performed without hesitation. Genetic testing is a sensitive and specific modality for the diagnosis of TSC. We report a case of TSC presenting with CTN only, in which genetic testing was very useful to confirm the diagnosis and to determine the appropriateness of further high-cost studies.