The distinct ophthalmic phenotype of Knobloch syndrome in children.
ABSTRACT Knobloch syndrome is defined as a triad of occipital defect, high myopia and vitreo-retinal degeneration (often with later retinal detachment); however, the ocular phenotype is not well defined. This report characterises eye findings of the syndrome in children with genetically confirmed disease.
Case series of Saudi children with previously documented homozygous mutations in COL18A1 or ADAMTS18.
All eight children (4-15 years old; five families) had smooth (cryptless) irides, high myopia (-10 to -20 dioptres) and distinctive vitreo-retinal degeneration consisting of diffuse very severe retinal pigment epithelium atrophic changes with prominent choroidal vessel show, macular atrophic lesions with or without a 'punched out' appearance and white fibrillar vitreous condensations. In two probands and a sibling, this distinctive retinal appearance was the basis for initial clinical diagnosis. Six children had temporal ectopia lentis and four had posterior perinuclear lens opacity. Additional features included developmental delay (two), epilepsy (one) and heterotopic grey matter in the lateral ventricles (one). Four children had no clinically discernible occipital defect.
Taken together, smooth iridies, ectopia lentis and characteristic vitreo-retinal degeneration seem pathognomonic. Although it is a defining feature of the syndrome, clinically discernible occipital defect is not a sine qua non for the diagnosis. Ophthalmologists are uniquely able to diagnose Knobloch syndrome.
- SourceAvailable from: Ivan Conte[show abstract] [hide abstract]
ABSTRACT: BACKGROUND: Inherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mutations in over 100 genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying a novel gene for an autosomal recessive form of early onset severe retinal dystrophy in a patient carrying no previously described mutations in known genes. METHODS: An integrated strategy including homozygosity mapping and whole exome sequencing was used to identify the responsible mutation. Functional tests were performed in the medaka fish (Oryzias latipes) model organism to gain further insight into the pathogenic role of the ADAMTS18 gene in eye and central nervous system (CNS) dysfunction. RESULTS: This study identified, in the analyzed patient, a homozygous missense mutation in the ADAMTS18 gene, which was recently linked to Knobloch syndrome, a rare developmental disorder that affects the eye and the occipital skull. In vivo gene knockdown performed in medaka fish confirmed both that the mutation has a pathogenic role and that the inactivation of this gene has a deleterious effect on photoreceptor cell function. CONCLUSION: This study reveals that mutations in the ADAMTS18 gene can cause a broad phenotypic spectrum of eye disorders and contribute to shed further light on the complexity of retinal diseases.Orphanet Journal of Rare Diseases 01/2013; 8(1):16. · 4.32 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Pediatric rhegmatogenous retinal detachments are rare, accounting for less than ten percent of all rhegmatogenous retinal detachments. While most retinal detachments in the adult population are related to posterior vitreous detachment, pediatric retinal detachment are often related to trauma or an underlying congenital abnormalities or genetic syndrome. The anatomy of pediatric eyes, the often late presentation of the disease, and the high incidence of bilateral pathology in children all pose significant challenges in the management of these patients. We discuss the epidemiology of pediatric rhegmatogenous retinal detachment, review the genetic syndromes associated with a high incidence of retinal detachment, and examine other common causes of retinal detachment in this age group. We then outline an approach to evaluation and management and describe the expected outcomes of repair of retinal detachment in the pediatric population.Saudi Journal of Ophthalmology 07/2012; 26(3):255-63.