Prevalence, multimodal imaging and genotype-phenotype assessment of trauma related subretinal fibrosis in stargardt disease.

BACKGROUND AND OBJECTIVES: Stargardt disease produces lipofuscin accumulation predisposing to subretinal fibrosis (SRFib) after ocular trauma. Noninvasive imaging techniques allow in vivo assessment. The purpose of this study is to determine the prevalence of SRFib in a cohort of Stargardt patients, the presence of history of ocular trauma, the clinical features and possible genotype-phenotype associations in Stargardt patients with SRFib. METHODS: We evaluated retrospectively 106 Stargardt patients and analysed the multimodal imaging and the genotype of patients with SRFib. RESULTS: Six patients exhibited SRFib, three of them with history of ocular trauma. Multimodal imaging showed extensive SRFib principally in the temporal midperipheral retina with no fluid associated. SRFib was better defined by short wavelength autofluorescence and spectral domain optical coherence tomography and appeared clinically stable over time. There was no particular genotype associated to SRFib. CONCLUSION: SRFib occurs in a significant percentage of patients with Stargardt disease and can be diagnosed through multimodal imaging regardless the history of trauma, further sustaining the importance of an appropriate imaging in such patients. No genotype-phenotype association has been established, supporting the traumatic etiology in half of cases. The remaining cases may be classified as idiopathic or have a minimal trauma occurring early in life that may be not recalled by the patients.

La secuenciación masiva (NGS) como método diagnóstico en la enfermedad de Stargardt / Next generation sequencing in the diagnosis of Stargardt's disease

Introducción: La enfermedad de Stargardt es la maculopatía más frecuente en la edad infantil y adulta. Presenta un origen genético por afectación principalmente del gen ABCA4 con herencia autosómica recesiva. Se trata de un gen con características especiales por su gran tamaño y comportamiento, mostrando una elevada tasa de mutaciones. La aparición, desarrollo y accesibilidad económica de las técnicas de secuenciación masiva permiten realizar el diagnóstico genético de la enfermedad de Stargardt. Pacientes y métodos: Se presentan 2 casos clínicos diagnosticados genéticamente de enfermedad de Stargardt mediante la realización de un panel de secuenciación masiva de 298 genes. Resultados: Los pacientes presentaban un fenotipo de maculopatía de ojo de buey con ausencia de flecks y las siguientes mutaciones: c.G5882A:p.Gly1961Glu y c.C3056T:p.T1019M para el caso 1; c.G5882A:p.Gly1961Glu y c.287del:p.Asn96Thrfs·19 para el caso 2. Ambos pacientes comparten la mutación c.G588A:2p.Gly1961Glu que explica su fenotipo similar característico. Conclusiones: La secuenciación masiva es especialmente útil en la enfermedad de Stargardt, pues el gen ABCA4 presenta un gran tamaño y elevada heterogeneidad polimórfica, que se traduce en una amplia variabilidad clínica (AU)

Introduction: Stargardt's disease is the most frequent form of inherited macular dystrophy in children and adults. It is a genetic eye disorder caused by mutations in ABCA4 gene with an autosomal recessive inheritance. ABCA4 is a very polymorphic and large gene containing 50 exons. The development of next generation sequencing (NGS) can be used for the genetic diagnosis of this disease. Patients and methods: A report is presented on two patients with a clinical diagnosis of Stargardt's disease whose genetic confirmation was performed by a NGS panel of 298 genes. Results: Clinically, the patients showed bull's eye maculopathy and absence of flecks, and genetically they shared the Gly1961Glu mutation that could explain their common phenotype, together with c.C3056T:p.T1019M for case 1, and c.287del:p.Asn96Thrfs·19 for case 2. Conclusions: NGS is particularly useful in the diagnosis of Stargardt's disease as ABCA4 is a large gene with a high allelic heterogeneity that causes a wide range of clinical manifestations (AU)

Next generation sequencing in the diagnosis of Stargardt's disease. / La secuenciación masiva (NGS) como método diagnóstico en la enfermedad de Stargardt.

INTRODUCTION: Stargardt's disease is the most frequent form of inherited macular dystrophy in children and adults. It is a genetic eye disorder caused by mutations in ABCA4 gene with an autosomal recessive inheritance. ABCA4 is a very polymorphic and large gene containing 50 exons. The development of next generation sequencing (NGS) can be used for the genetic diagnosis of this disease. PATIENTS AND METHODS: A report is presented on two patients with a clinical diagnosis of Stargardt's disease whose genetic confirmation was performed by a NGS panel of 298 genes. RESULTS: Clinically, the patients showed bull's eye maculopathy and absence of flecks, and genetically they shared the Gly1961Glu mutation that could explain their common phenotype, together with c.C3056T:p.T1019M for case 1, and c.287del:p.Asn96Thrfs*19 for case 2. CONCLUSIONS: NGS is particularly useful in the diagnosis of Stargardt's disease as ABCA4 is a large gene with a high allelic heterogeneity that causes a wide range of clinical manifestations.

Cortical Blindness in a Child Secondary to Mycoplasma pneumoniae Infection.

Our objective is to present a case of an uncommon complication associated with Mycoplasma pneumoniae infection in a child where cortical blindness was the main clinical feature. Stroke due to an infection by M. pneumoniae is very uncommon. No consensus has been reached on the pathogenesis, although several pathogenic mechanisms have been proposed. Occlusion of posterior cerebral circulation is the most uncommon central nervous system complication of M. pneumoniae infection being reported. Symptoms are usually hemiplegia and dysarthria. We report a case of a 6-year-old boy who suffered cortical blindness due to a stroke 2 days after M. pneumoniae infection. This is the first case of documented cortical blindness due to posterior cerebral arteries occlusion in children after M. pneumoniae infection.