RESUMO
BACKGROUND: Danon disease is a neuromuscular disorder with variable expression in the eye. We describe a family with Danon disease and cone-rod dystrophy (CRD). METHODS: Affected males of one family with Danon were invited for an extensive ophthalmologic examination, including color vision testing, fundus photography, Goldmann perimetry, full-field electroretinogram (ERG), and SD-OCT. Previous ophthalmologic data were retrieved from medical charts. The LAMP2 and RPGR gene were analyzed by direct sequencing. RESULTS: Two siblings had no ocular phenotype. The third sibling and a cousin developed CRD leading to legal blindness. Visual acuity deteriorated progressively over time, color vision was severely disturbed, and ERG showed reduced photopic and scotopic responses. SD-OCT revealed thinning of the photoreceptor and RPE layer. Visual fields demonstrated central scotoma. The causal mutation was p.Gly384Arg in LAMP2; no mutations were found in RPGR. CONCLUSIONS: This is the first description of CRD in Danon disease. The retinal phenotype was a late onset but severe dystrophy characterized by loss of photoreceptors and RPE cells. With this report, we highlight the importance of a comprehensive ophthalmologic examination in the clinical work-up of Danon disease.
Assuntos
Doença de Depósito de Glicogênio Tipo IIb/diagnóstico , Retinose Pigmentar/diagnóstico , Idoso , Eletrorretinografia , Proteínas do Olho/genética , Genótipo , Doença de Depósito de Glicogênio Tipo IIb/genética , Doença de Depósito de Glicogênio Tipo IIb/fisiopatologia , Humanos , Proteína 2 de Membrana Associada ao Lisossomo , Proteínas de Membrana Lisossomal/genética , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Linhagem , Fenótipo , Reação em Cadeia da Polimerase , Retinose Pigmentar/genética , Retinose Pigmentar/fisiopatologia , Irmãos , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Testes de Campo VisualRESUMO
PURPOSE: The assets of this report are a thorough description of new clinical findings, namely the combination of ptosis, extraocular motility disorder and myopia, in consequence of prolonged survival in classic infantile-onset Pompe disease through enzyme therapy. DESIGN: Single case description. RESULTS: This manuscript describes a combination of ptosis, extraocular motility disorder and myopia in a 4.5-year-old patient with classic infantile-onset Pompe disease, who survived through enzyme therapy. This patient was treated with a bilateral frontalis suspension (modified Crawford technique) using prolene 3-0 sutures. CONCLUSIONS: The combination of ptosis, extraocular motility disorder and myopia, is a new clinical finding in children with classic infantile-onset Pompe disease.
Assuntos
Blefaroptose/diagnóstico , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Miopia/diagnóstico , Transtornos da Motilidade Ocular/diagnóstico , Pré-Escolar , Humanos , Masculino , Músculos Oculomotores/cirurgia , Procedimentos Cirúrgicos OftalmológicosRESUMO
OBJECTIVE: To investigate the genetic causes of complete and incomplete achromatopsia (ACHM) and assess the association between disease-causing mutations, phenotype at diagnosis, and visual prognosis. DESIGN: Clinic-based, longitudinal, multicenter study. PARTICIPANTS: Probands with complete ACHM (n = 35), incomplete ACHM (n = 26), or nonspecific ACHM (n = 2) and their affected relatives (n = 18) from various ophthalmogenetic clinics in The Netherlands. METHODS: Ophthalmologic clinical data were assessed over a life time and were registered from medical charts and updated by ophthalmologic examination. Mutations in the CNGB3, CNGA3, and GNAT2 genes were analyzed by direct sequencing. MAIN OUTCOME MEASURES: Genetic mutations and clinical course of ACHM. RESULTS: CNGB3 mutations were identified in 55 of 63 (87%) of probands and all caused premature truncation of the protein. The most common mutation was p.T383IfsX13 (80%); among the 4 other mutations was the novel frameshift mutation p.G548VfsX35. CNGA3 mutations were detected in 3 of 63 (5%) probands; all caused an amino acid change of the protein. No mutations were found in the GNAT2 gene. The ACHM subtype, visual acuity, color vision, and macular appearance were equally distributed among the CNGB3 genotypes, but were more severely affected among CNGA3 genotypes. Visual acuity deteriorated from infancy to adulthood in 12% of patients, leading to 0.10 in 61%, and even lower than 0.10 in 20% of patients. CONCLUSIONS: In this well-defined cohort of ACHM patients, the disease seemed much more genetically homogeneous than previously described. The CNGB3 gene was by far the most important causal gene, and T383IfsX13 the most frequent mutation. The ACHM subtype did not associate with a distinct genetic etiology, nor were any other genotype-phenotype correlations apparent. The distinction between complete and incomplete subtypes of ACHM has no clinical value, and the assumption of a stationary nature is misleading.