RESUMO
INTRODUCTION: Ritscher-Schinzel syndrome (also known as cranio-cerebello-cardiac dysplasia or 3C syndrome) is a rare genetic syndrome that is mainly characterised by the association of cardiac and craniofacial anomalies together with others affecting the posterior fossa. PATIENTS AND METHODS: We report on 26 patients with Ritscher-Schinzel syndrome at a hospital in Medellin, in the Department of Antioquia, Colombia. RESULTS: Males account for 69% of this cohort. The mean age of the cohort was 30 months, and 42% were under the age of one year at the time of diagnosis. All of them presented ocular disorders, and megalocornea was the most frequent ocular manifestation (69%), whereas low-set ears (80.7%) and septal heart defects (68.7%) were the most common facial and cardiac malformations, respectively. The most frequent malformations of the posterior fossa were megacisterna magna (31.8%) and Dandy-Walker malformation (27%). 84% of the cases had delayed neurodevelopment or intellectual disability. Skeletal manifestations were frequent: the group consisting of camptodactyly, single palmar crease, overlapping fingers, vertical talus and nail hypoplasia were found in hands and feet in 96% of the cases. CONCLUSIONS: Ritscher-Schinzel syndrome is a heterogeneous syndrome from the genetic and clinical point of view. These results suggest that the skeletal and ocular abnormalities that were observed can facilitate the phenotypic diagnosis. However, it is necessary to conduct further studies that allow us to gain a deeper knowledge of its prevalence and help identify other genes involved in this syndrome.
TITLE: Descripcion fenotipica de 26 pacientes con sindrome de Ritscher-Schinzel (displasia craneo-cerebelo-cardiaca o sindrome 3C).Introduccion. El sindrome de Ritscher-Schinzel (tambien conocido como displasia craneo-cerebelo-cardiaca o sindrome 3C) es un sindrome genetico raro que se caracteriza principalmente por la asociacion de anomalias cardiacas, craneofaciales y de la fosa posterior. Pacientes y metodos. Se describen 26 pacientes con sindrome de Ritscher-Schinzel pertenecientes a un hospital de Medellin en el departamento de Antioquia, Colombia. Resultados. La presente cohorte esta compuesta en un 69% por hombres. La mediana de edad de la cohorte fue de 30 meses y el 42% tenia menos de 1 año de edad en el momento del diagnostico. Todos presentaban afectacion ocular, y la megalocornea fue la manifestacion ocular mas frecuente (69%), mientras que las orejas de implantacion baja (80,7%) y los defectos cardiacos septales (68,7%) fueron las malformaciones faciales y cardiacas mas comunes, respectivamente. Las malformaciones de la fosa posterior mas frecuentes fueron megacisterna magna (31,8%) y malformacion de Dandy-Walker (27%). El 84% tenia retraso del neurodesarrollo o discapacidad intelectual. Las manifestaciones esqueleticas fueron frecuentes: el conjunto de camptodactilia, pliegue palmar unico, dedos sobrelapados, astragalo vertical e hipoplasia ungueal en las manos y los pies se hallo en el 96% de los casos. Conclusiones. El sindrome de Ritscher-Schinzel es heterogeneo desde el punto de vista genetico y clinico. Estos resultados sugieren que las anormalidades esqueleticas y oculares observadas pueden facilitar el diagnostico fenotipico. No obstante, es necesario realizar estudios adicionales que permitan conocer mejor su prevalencia y facilitar la identificacion de otros genes implicados en este sindrome.
Assuntos
Anormalidades Múltiplas/genética , Cerebelo/anormalidades , Fossa Craniana Posterior/anormalidades , Anormalidades Craniofaciais/genética , Síndrome de Dandy-Walker/genética , Deficiências do Desenvolvimento/genética , Anormalidades do Olho/genética , Comunicação Interatrial/genética , Deficiência Intelectual/genética , Anormalidades Múltiplas/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Colômbia , Córnea/anormalidades , Anormalidades Craniofaciais/patologia , Síndrome de Dandy-Walker/patologia , Feminino , Deformidades Congênitas do Pé/genética , Deformidades Congênitas da Mão/genética , Comunicação Interatrial/patologia , Humanos , Lactente , Recém-Nascido , Masculino , Fenótipo , Estudos Retrospectivos , SíndromeAssuntos
Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/genética , Interferon gama/genética , Mycobacterium tuberculosis/isolamento & purificação , Osteíte/microbiologia , Infecções por Salmonella/diagnóstico , Salmonella/isolamento & purificação , Tuberculose Pulmonar/etiologia , Antibióticos Antituberculose/uso terapêutico , Pré-Escolar , Feminino , Humanos , Osteíte/diagnóstico por imagem , Osteíte/prevenção & controle , Infecções por Salmonella/tratamento farmacológico , Infecções por Salmonella/etiologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/patologia , Tomografia Computadorizada por Raios X , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
Patients with adenosine deaminase (ADA) deficiency exhibit spontaneous and partial clinical remission associated with somatic reversion of inherited mutations. We report a child with severe combined immunodeficiency (T-B- SCID) due to ADA deficiency diagnosed at the age of 1 month, whose lymphocyte counts including CD4+ and CD8+ T and NK cells began to improve after several months with normalization of ADA activity in Peripheral blood lymphocytes (PBL), as a result of somatic mosaicism caused by monoallelic reversion of the causative mutation in the ADA gene. He was not eligible for haematopoietic stem cell transplantation (HSCT) or gene therapy (GT); therefore he was placed on enzyme replacement therapy (ERT) with bovine PEG-ADA. The follow-up of metabolic and immunologic responses to ERT included gradual improvement in ADA activity in erythrocytes and transient expansion of most lymphocyte subsets, followed by gradual stabilization of CD4+ and CD8+ T (with naïve phenotype) and NK cells, and sustained expansion of TCRγδ+ T cells. This was accompanied by the disappearance of the revertant T cells as shown by DNA sequencing from PBL. Although the patient's clinical condition improved marginally, he later developed a germinal cell tumour and eventually died at the age of 67 months from sepsis. This case adds to our current knowledge of spontaneous reversion of mutations in ADA deficiency and shows that the effects of the ERT may vary among these patients, suggesting that it could depend on the cell and type in which the somatic mosaicism is established upon reversion.