ABSTRACT
Abstract There are more than 150 different rare genetic kidney diseases. They can be classified according to diagnostic findings as (i) disorders of growth and structure, (ii) glomerular diseases, (iii) tubular, and (iv) metabolic diseases. In recent years, there has been a shift of paradigm in this field. Molecular testing has become more accessible, our understanding of the underlying pathophysiologic mechanisms of these diseases has evolved, and new therapeutic strategies have become more available. Therefore, the role of nephrologists has progressively shifted from a mere spectator to an active player, part of a multidisciplinary team in the diagnosis and treatment of these disorders. This article provides an overview of the recent advances in rare hereditary kidney disorders by discussing the genetic aspects, clinical manifestations, diagnostic, and therapeutic approaches of some of these disorders, named familial focal and segmental glomerulosclerosis, tuberous sclerosis complex, Fabry nephropathy, and MYH-9 related disorder.
Resumo As doenças renais genéticas raras compreendem mais de 150 desordens. Elas podem ser classificadas segundo achados diagnósticos como (i) distúrbios do crescimento e estrutura, (ii) doenças glomerulares, (iii) tubulares e (iv) metabólicas. Nos últimos anos, houve uma mudança de paradigma nesse campo. Os testes moleculares tornaram-se mais acessíveis, nossa compreensão sobre os mecanismos fisiopatológicos subjacentes a essas doenças evoluiu e novas estratégias terapêuticas foram propostas. Portanto, o papel do nefrologista mudou progressivamente de mero espectador a participante ativo, parte de uma equipe multidisciplinar, no diagnóstico e tratamento desses distúrbios. O presente artigo oferece um panorama geral dos recentes avanços a respeito dos distúrbios renais hereditários raros, discutindo aspectos genéticos, manifestações clínicas e abordagens diagnósticas e terapêuticas de alguns desses distúrbios, mais especificamente a glomeruloesclerose segmentar e focal familiar, complexo da esclerose tuberosa, nefropatia de Fabry e doença relacionada ao MYH9.
Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adult , Genetic Diseases, Inborn/genetics , Kidney/physiopathology , Kidney Diseases/congenital , Kidney Diseases/diagnosis , Thrombocytopenia/congenital , Thrombocytopenia/diagnosis , Thrombocytopenia/therapy , Tuberous Sclerosis/therapy , Genetic Testing/methods , Fabry Disease/diagnosis , Fabry Disease/genetics , Fabry Disease/therapy , Interdisciplinary Communication , Glomerular Filtration Rate/physiology , Hearing Loss, Sensorineural/diagnosis , Genetic Diseases, Inborn/diagnosis , Kidney Tubules/pathology , Metabolic Diseases/pathology , Nephrology/standardsABSTRACT
Abstract: Tuberous sclerosis complex is a multisystemic, autosomal dominant genetic disorder with complete penetrance, that can evolve with hamartomas in multiple organs, such as skin, central nervous system, kidney and lung. Due to the wide phenotypic variability, the disease is often not recognized. Tuberous sclerosis complex affects one in 10,000 newborns and most patients are diagnosed during the first 15 months of life. The diagnostic criteria for tuberous sclerosis were reviewed in 2012, at the second International Tuberous Sclerosis Complex Consensus Conference. The diagnosis is based on genetic criteria, by the identification of inactivating pathogenic mutation of tumor suppressor genes TSC1 and TSC2, and clinical criteria, including cutaneous, renal, pulmonary, cardiac and neurological manifestations. The treatment of tuberous sclerosis complex consists, mainly, in management of the symptoms caused by hamartomas and in prevention of organ failure. Multidisciplinary approach is recommended, in order to obtain better clinical outcomes.
Subject(s)
Humans , Tuberous Sclerosis/diagnosis , Hamartoma/diagnosis , Tuberous Sclerosis/genetics , Tuberous Sclerosis/therapy , Sirolimus/therapeutic use , Hamartoma/genetics , Hamartoma/therapy , Immunosuppressive Agents/therapeutic use , MutationABSTRACT
El diagnóstico es Rabdomiomas cardiacos/ Esclerosis tuberosa.
Subject(s)
Humans , Male , Infant, Newborn , Tuberous Sclerosis/diagnosis , Tuberous Sclerosis , Tuberous Sclerosis/therapy , Infant, Newborn , Heart Neoplasms/diagnosis , Heart Neoplasms , Heart Neoplasms , Rhabdomyoma/diagnosis , Rhabdomyoma , Rhabdomyoma/therapy , ArgentinaABSTRACT
Tuberous Sclerosis Complex, also known as Epiloia or Bourneville-Pringle disease is an autosomal dominant neurocutaneous syndrome with variable clinical expression. It is a multisystem disorder that may be associated with hamartomas in multiple organs in an unpredictable manner. The dermatologist plays an essential role in the history of the disease, since skin manifestations represent the most prevalent clinical features, enabling early diagnosis and intervention in its natural course. This article aims to inform the scientific community about advances made in the study of genetics and molecular biology. Recent findings regarding stimulation of tumor growth have been changing the history of this condition, making therapeutic trials with topical and systemic drugs possible. Knowledge of these topics enables better management of the patients affected, since tissue replacement by tumors can result in significant morbidity and mortality.
A Esclerose Tuberosa, também conhecida como Epilóia ou Facomatose de Pringle-Bourneville, é uma síndrome neurocutânea de caráter autossômico dominante com expressões clínicas variadas. É uma doença multissistêmica que pode cursar com hamartomas em diversos órgãos, de forma imprevisível. O dermatologista tem papel essencial na história da doença, uma vez que as afecções cutâneas representam as mais prevalentes apresentações clínicas, possibilitando assim o diagnóstico precoce da síndrome e intervenção na sua evolução natural. O presente artigo tem o objetivo de atualizar a comunidade científica sobre avanços alcançados no estudo genético e biologia molecular. Recentes descobertas sobre o estímulo do crescimento tumoral vêm mudando a evolução desta patologia, possibilitando ensaios terapêuticos com drogas tópicas e sistêmicas. O conhecimento destes aspectos possibilita melhor condução dos pacientes acometidos, dado que a substituição tumoral dos diversos tecidos pode resultar em relevante morbidade e mortalidade.
Subject(s)
Humans , Skin Diseases , Tuberous Sclerosis , Skin Diseases/diagnosis , Skin Diseases/etiology , Skin Diseases/therapy , Tuberous Sclerosis/diagnosis , Tuberous Sclerosis/etiology , Tuberous Sclerosis/therapyABSTRACT
La esclerosis tuberosa es un cuadro sistémico, cuya característica principal es la presencia de hamartomas múltiples que afectan fundamentalmente la piel, el sistema nervioso central, los ojos, el corazón, los riñones, los pulmones y los huesos. Se transmite en forma autosómica dominante y ocurre por mutaciones en dos genes, TCS1 y TCS2, que codifican las proteínas hamartina y tuberina, respectivamente, y se comportan como supresores tumorales. Existen criterios diagnósticos mayores y menores bien establecidos para su reconocimiento y, por ser una genodermatosis compleja, requiere un manejo interdisciplinario. El dermatólogo tiene un rol importante en su reconocimiento, ya que varias de las manifestaciones clínicas tempranas son cutáneas.
Tuberous sclerosis is a systemic disorder characterized by multiple hamartomas that mainly affect central nervous system, eyes, heart, kidneys, lungs and bones. It is inherited as an autosomal dominant trait and determined by the mutations of two genes, TCS1 and TCS2, that codify the proteins hamartine and tuberine respectively and are tumoral suppressor genes. Well established major and minor diagnostic criteria exist for its recognition. This is a complex genetic disease and patients need a multidisciplinary follow-up. Dermatologists have an important role in its recognition once several early manifestations are cutaneous.
Subject(s)
Humans , Male , Female , Tuberous Sclerosis/diagnosis , Tuberous Sclerosis/genetics , Tuberous Sclerosis/pathology , Tuberous Sclerosis/therapy , Adenoma , Angiofibroma , Diagnosis, Differential , Epilepsy , IntelligenceABSTRACT
Tuberous sclerosis is a rare genetic disease of autosomal dominant inheritance, associated with hamartomata formation in several organs and various skin findings. A case of young male is presented here with multiple fibromas on right side of his face, peri-ungual fibromas in right index and middle fingers and right second toe, a small shagreen plaque over right lower back and multiple, ill-defined hypopigmented patches over his right side of the trunk and right buttocks. Fundoscopic examination revealed retinal phacomas on right side. CT-scan brain showed right-sided paraventricular calcification
Subject(s)
Humans , Male , Tuberous Sclerosis/therapy , Hamartoma/diagnosis , Fibroma/diagnosis , Skin/pathologyABSTRACT
We report a 26 years old male with a tuberous sclerosis with multiple and bilateral kidney cysts and angiomyolipomas. The patient presented to the emergency room with a severe abdominal pain and anemia, secondary to a bleeding angiomyolipoma. The patient rejected blood transfusions due to his religious beliefs. A selective angiography was performed confirming diagnosis and the lesion artery was selectively embolized, stopping the bleeding immediately. The patient had a satisfactory evolution thereafter. This is a rare lesion and the fact that the patient was a Jehovah witness that rejected blood transfusions, required an innovative medical approach
Subject(s)
Humans , Male , Adult , Tuberous Sclerosis/diagnosis , Christianity , Hemorrhage/therapy , Tuberous Sclerosis/therapy , Angiomyolipoma/diagnosis , Epilepsy , Hemorrhage/etiology , Embolization, Therapeutic , Blood TransfusionABSTRACT
Se reportan dos casos de esclerosis tuberosa (un paciente masculino de 34 y otra de 17 años de edad) tratados en la Unidad De Cuidados Intensivos del Hospital General de Zona Núm. 1 de Tepic, Nayarit. Los dos presentaron convulsiones desde la infancia, manchas blancas y ocre en dorso y cara, retraso mental evolutivo, pequeñas nodulaciones de 2 a 3 mm en posición centrofacial y ortejos. Ambos fueron tratados previamente con diversos anticonvulsivantes con el diagnóstico único de epilepsia evolutiva. Ingresaron a la Unidad de Cuidados Intensivos por status epilepticus que ameritó tratamiento a base de coma barbitúrico
Subject(s)
Humans , Male , Female , Adult , Tuberous Sclerosis/diagnosis , Tuberous Sclerosis/therapy , Status Epilepticus/etiology , Status Epilepticus/therapyABSTRACT
Hace una revisión sobre la etiología genética, manifestaciones neuro-psiquiátricas, cutáneas y otras de la esclerosis tuberosa. Además se presentan los criterios diagnósticos, pronóstico y tratamiento...
Subject(s)
Humans , Tuberous Sclerosis/diagnosis , Tuberous Sclerosis/etiology , Tuberous Sclerosis/genetics , Tuberous Sclerosis/therapyABSTRACT
Se presenta un paciente masculino con epiloia, con lesiones de angiofibromas a nivel facial que causan desfiguración. Se realiza tratamiento combinado de electrocirugía y dermabrasión con técnica tumescente, con muy buenos resultados
Subject(s)
Adult , Humans , Male , Angiofibroma/therapy , Dermabrasion/instrumentation , Dermabrasion/statistics & numerical data , Electrosurgery/instrumentation , Electrosurgery/statistics & numerical data , Tuberous Sclerosis/physiopathology , Tuberous Sclerosis/therapyABSTRACT
Se presentan 3 pacientes postpuber con esclerosis tuberosa con afectacion cutaneovisceral y sin evidencia de retardo mental ni epilepsia,en quienes se realizo tratamiento de los angiofibromas utilizando nitrogeno liquido con cono spray y punta de contacto ocasional.En todos el resultado fue cosmeticamente aceptable y no se produjeron efectos indeseables.Consideram,os de eleccion el metodo utilizado por los resultados obtenidos y ventajas del mismo