Nystagmus associated with macular dysplasia.

Purpose: To describe Optical Coherence Tomography (OCT) findings of the macula in patients with nystagmus, mainly the relationship between spectral-domain OCT (SD-OCT) images and nystagmus in macular dysplasia.Methods: In this study, 17 cases (29 eyes) with congenital macular abnormalities in patients with albinism, macular heterotopias, congenital aniridia, foveal hypoplasia, congenital macular coloboma, and congenital retinoschisis were retrospectively analyzed. Patients underwent multimodal retinal imaging examinations including ultra-widefield fundus imaging, SD-OCT, autofluorescence, and visual field. When the pit was not clearly presented, SD-OCT imaging was centered at the expected foveal center.Results: In cases of oculocutaneous albinism SD-OCT showed the absence of the foveal pit and increased foveal thickness, with nystagmus. Their fundus revealed a lack of pigment in retinal pigment epithelium with visible large choroidal vessels. SD-OCT in congenital aniridia showed a planar fovea in the macula with the lack of a foveal pit and nystagmus. SD-OCT showed the absence of a foveal pit in foveal hypoplasia with nystagmus. In cases of monocular macular heterotopia, no nystagmus was found; the fellow eye had good vision and the macular morphology was usually normal. Nystagmus was not found in patients with congenital macular coloboma and congenital retinoschisis in this study.Conclusion: SD-OCT plays an important role in the diagnosis and prognosis of macular dysplasia in patients with nystagmus. Absence of a normal foveal pit is an OCT-imaging characteristic of macular dysplasia associated with nystagmus.

Congenital muscular dystrophy-dystroglycanopathy, type A, featuring bilateral retinal dysplasia and vertical angle kappa.

Muscular dystrophy-dystroglycanopathy type A (MDDGA3), one of a group of diseases collectively known as congenital muscular dystrophies, is an alpha-dystroglycanopathy with characteristic brain and ocular abnormalities. We report the case of a 9-month-old boy with developmental delay whose family sought evaluation for esotropia. Subsequent examination, imaging, and testing revealed significant motor and cognitive delay, marked weakness with appendicular spasticity, and a diffuse brain malformation. In addition, the patient had poor visual acuity, nystagmus, optic nerve hypoplasia, bilateral retinal dysplasia and retinal dragging with a large vertical angle kappa, and an avascular peripheral retina. Genetic testing revealed two known heterozygous mutations in the POMGnT1 gene confirming MDDGA3. He was treated with botulinum toxin injections for his strabismus and continues to be followed, with planned laser ablation of the peripheral avascular retina.

A homozygous deleterious CDK10 mutation in a patient with agenesis of corpus callosum, retinopathy, and deafness.

The primary cilium is a key organelle in numerous physiological and developmental processes. Genetic defects in the formation of this non-motile structure, in its maintenance and function, underlie a wide array of ciliopathies in human, including craniofacial, brain and heart malformations, and retinal and hearing defects. We used exome sequencing to study the molecular basis of disease in an 11-year-old female patient who suffered from growth retardation, global developmental delay with absent speech acquisition, agenesis of corpus callosum and paucity of white matter, sensorineural deafness, retinitis pigmentosa, vertebral anomalies, patent ductus arteriosus, and facial dysmorphism reminiscent of STAR syndrome, a suspected ciliopathy. A homozygous variant, c.870_871del, was identified in the CDK10 gene, predicted to cause a frameshift, p.Trp291Alafs*18, in the cyclin-dependent kinase 10 protein. CDK10 mRNAs were detected in patient cells and do not seem to undergo non-sense mediated decay. CDK10 is the binding partner of Cyclin M (CycM) and CDK10/CycM protein kinase regulates ciliogenesis and primary cilium elongation. Notably, CycM gene is mutated in patients with STAR syndrome. Following incubation, the patient cells appeared less elongated and more densely populated than the control cells suggesting that the CDK10 mutation affects the cytoskeleton. Upon starvation and staining with acetylated-tubulin, γ-tubulin, and Arl13b, the patient cells exhibited fewer and shorter cilia than control cells. These findings underscore the importance of CDK10 for the regulation of ciliogenesis. CDK10 defect is likely associated with a new form of ciliopathy phenotype; additional patients may further validate this association.

Ocular manifestations of microcephaly with or without chorioretinopathy, lymphedema or intellectual disability (MCLID) syndrome associated with mutations in KIF11.

PURPOSE: Microcephaly with or without chorioretinopathy, lymphedema or intellectual disability (MCLID) is an autosomal dominant condition. Mutations in KIF11 have been found to be causative in approximately 75% of cases. This study describes the ocular phenotype in patients with confirmed KIF11 mutations. METHODS: Standard ophthalmic examination and investigation including visual acuity, refraction and fundus examination was carried out in all patients. Fundus autofluorescence imaging (FAF) was performed in three patients, and four patients underwent spectral domain optical coherence tomography (OCT). Flash electroretinography (ERG) was performed in seven patients, and five underwent additional pattern electroretinography (PERG). RESULTS: The patients ranged in age from 2 to 10 years. Most presented with visual acuity loss. Fundus examination revealed lacunae of chorioretinal atrophy. Pigmentary macular changes and optic disc pallor were present in three of seven patients. Fundus autofluorescence demonstrated hypoautofluorescence at the macula in two of three patients. The lacunae of chorioretinal atrophy were hypoautofluorescent. The OCT showed atrophic maculae in three of four patients. Follow-up in one patient showed no deterioration of the vision over a 9-year period. The lesions appear not to be progressive on the follow-up imaging. Electrophysiology showed generalized rod and cone dysfunction and severe macular dysfunction. Inner retinal dysfunction was evident in three of seven patients. CONCLUSIONS: Patients with KIF11 mutations show a specific ocular phenotype with variable expressivity and intrafamilial variability. Macular atrophy and dysfunction have not been consistently documented before. The fundus lesions appear non-progressive. The findings assist in providing an accurate diagnosis and thus improving the management and follow-up of patients with this syndrome.

Retinal dysplasia in the crab-eating fox (Cerdocyon thous) / Displasia retiniana em cachorro-do-mato (Cerdocyon thous)

Previously described in humans and domestic animals, retinal dysplasia has three clinical forms: focal/multifocal, geographic and total. A young orphan crab-eating fox (Cerdocyon thous) from wildlife, male, approximately 45 days old referred to the Wildlife Medicine and Ophthalmology Services of the "Governador Laudo Natel" Veterinary Hospital of the Universidade Estadual Paulista, Jaboticabal Campus, SP, Brazil, where it received primary outpatient care. The patient was in good general health condition, without hematological, biochemistry or serological alterations and no signs of visual impairment. Indirect binocular ophthalmoscopy showed retinal changes in the left eye, distributed over the tapetal area in the form of grayish folds and rosettes. In the affected areas, tapetal reflectivity was reduced. No other ophthalmic abnormalities were observed. This is the first report of retinal dysplasia in the crab-eating fox (Cerdocyon thous) from wildlife.(AU)

Descrita no homem e em animais domésticos, a displasia de retina, se apresenta nas formas focal/multifocal, geográfica e completa. Um espécime de cachorro-do-mato (Cerdocyon thous) de vida livre, macho, com 45 dias de vida foi capturado e encaminhado aos Serviços de Medicina de Animais Selvagens e de Oftalmologia do Hospital Veterinário "Governador Laudo Natel" da Universidade Estadual Paulista ­ Unesp, Câmpus Jaboticabal-SP, Brasil, onde recebeu atendimento primário ambulatorial. O paciente apresentava-se em bom estado geral, sem alterações hematológicas e sorológicas, e não havia sinais de déficit visual. A oftalmoscopia binocular indireta mostrou alterações retinianas no olho esquerdo, distribuídas na área tapetal na forma de pregas e de rosetas de coloração acinzentada. Nas áreas acometidas, a reflectividade tapetal estava reduzida. Não foram observadas outras alterações oftálmicas. Trata-se do primeiro relato de literatura sobre displasia retiniana em cachorrodo-mato (Cerdocyon thous).(AU)

Acute Blindness.

Sudden loss of vision is an ophthalmic emergency with numerous possible causes. Abnormalities may occur at any point within the complex vision pathway, from retina to optic nerve to the visual center in the occipital lobe. This article reviews specific prechiasm (retina and optic nerve) and cerebral cortical diseases that lead to acute blindness. Information regarding specific etiologies, pathophysiology, diagnosis, treatment, and prognosis for vision is discussed.

Peters anomaly in cri-du-chat syndrome.

The cri-du-chat syndrome is a rare genetic disorder caused by deletions in the short arm of chromosome 5. It presents with a distinctive catlike high-pitched cry, psychomotor delays, microcephaly, craniofacial abnormalities, and, in many cases, ocular findings. We report the first child with cri-du-chat and the findings of unilateral corneal staphyloma due to Peters anomaly and retinal dysplasia.

Retinal dysplasia of holoprosencephaly.

Retinal dysplasia occurs in the setting of sporadic and syndromic holoprosencephaly, which often has associated ocular malformations. The pathology of this dysplasia, which includes rosettes, has been previously described. However, its funduscopic findings have not been well documented. The authors present the fundus images of a patient with severe holoprosencephaly with retinal dysplasia and bilateral optic nerve colobomas that resulted in death 2 weeks after birth.

Congenital microcephaly and chorioretinopathy due to de novo heterozygous KIF11 mutations: five novel mutations and review of the literature.

The microcephaly-lymphedema-chorioretinal dysplasia (MLCRD) syndrome is a distinct microcephaly syndrome. The hallmark features, microcephaly, chorioretinopathy, and lymphedema are frequently recognized at birth. Another clinical entity, the chorioretinal dysplasia, microcephaly and mental retardation syndrome (CDMMR) is a highly overlapping syndrome characterized by more variable lymphedema. Recently, heterozygous mutations in KIF11, a gene encoding a critical spindle motor protein of the Kinesin family, have been reported in individuals with MLCRD, and in individuals with CDMMR. This finding is suggestive of a single clinically variable spectrum. Here, we report on de novo novel mutations of KIF11 in five individuals with severe microcephaly, marked simplification of the gyral pattern on neuroimaging, bilateral chorioretinopathy, and developmental delay. Three patients had congenital lymphedema, and one had congenital bilateral sensorineural hearing loss. This report, therefore, further expands the clinical and molecular spectrum of KIF11-associated microcephaly.

Phenotypic overlap between familial exudative vitreoretinopathy and microcephaly, lymphedema, and chorioretinal dysplasia caused by KIF11 mutations.

IMPORTANCE: Retinal detachment with avascularity of the peripheral retina, typically associated with familial exudative vitreoretinopathy (FEVR), can result from mutations in KIF11, a gene recently identified to cause microcephaly, lymphedema, and chorioretinal dysplasia (MLCRD) as well as chorioretinal dysplasia, microcephaly, and mental retardation (CDMMR). Ophthalmologists should be aware of the range of presentations for mutations in KIF11 because the phenotypic distinction between FEVR and MLCRD/CDMMR portends management implications in patients with these conditions. OBJECTIVE: To identify gene mutations in patients who present with a FEVR phenotype and explore the spectrum of ocular and systemic abnormalities caused by KIF11 mutations in a cohort of patients with FEVR or microcephaly in conjunction with chorioretinopathy or FEVR. DESIGN, SETTING, AND PARTICIPANTS: Clinical data and DNA were collected from each participant between 1998 and 2013 from the clinical practices of ophthalmologists and clinical geneticists internationally. Twenty-eight FEVR probands with diagnoses made by the referring physician and without a known FEVR gene mutation, and 3 with microcephaly and chorioretinopathy, were included. At least 1 patient in each pedigree manifested 1 or more of the following: macular dragging, partial retinal detachment, falciform folds, or total retinal detachment. EXPOSURES: Whole-exome sequencing was conducted on affected members in multiplex pedigrees, and Sanger sequencing of the 22 exons of the KIF11 gene was performed on singletons. Clinical data and history were collected and reviewed. MAIN OUTCOMES AND MEASURES: Identification of mutations in KIF11. RESULTS: Four novel heterozygous KIF11 mutations and 1 previously published mutation were identified in probands with FEVR: p.A218Gfs*15, p.E470X, p.R221G, c.790-1G>T, and the previously described heterozygous p.R47X. Documentation of peripheral avascular areas on intravenous fluorescein angiography was possible in 2 probands with fibrovascular proliferation demonstrating phenotypic overlap with FEVR. CONCLUSIONS AND RELEVANCE: Mutations in KIF11 cause a broader spectrum of ocular disease than previously reported, including retinal detachment. The KIF11 gene likely plays a role in retinal vascular development and mutations in this gene can lead to clinical overlap with FEVR. Cases of FEVR should be carefully inspected for the presence of microcephaly as a marker for KIF11-related disease to enhance the accuracy of the prognosis and genetic counseling.

A novel KIF11 mutation in a Turkish patient with microcephaly, lymphedema, and chorioretinal dysplasia from a consanguineous family.

Microcephaly-lymphedema-chorioretinal dysplasia (MLCRD) syndrome is a rare syndrome that was first described in 1992. Characteristic craniofacial features include severe microcephaly, upslanting palpebral fissures, prominent ears, a broad nose, and a long philtrum with a pointed chin. Recently, mutations in KIF11 have been demonstrated to cause dominantly inherited MLCRD syndrome. Herein, we present a patient with MLCRD syndrome whose parents were first cousins. The parents are unaffected, and thus a recessive mode of inheritance for the disorder was considered likely. However, the propositus carries a novel, de novo nonsense mutation in exon 2 of KIF11. The patient also had midline cleft tongue which has not previously been described in this syndrome.

Microcephaly-lymphedema-chorioretinal dysplasia associated with pachymicrogyria and atrophy of the cerebellar vermis: an integration of brain-ocular migration disorders.

BACKGROUND: Microcephaly-lymphedema-chorioretinal dysplasia (OMIM 152950) is a rare malformative inherited disorder that can be associated with other systemic features. Other ocular and brain anomalies rather than microcephaly and chorioretinal dysplasia have been inconstantly reported in this syndrome. METHODS: We present a case of microcephaly-lymphedema-chorioretinal dysplasia with a dysmorphic facies, hypertonicity in the extremities and neuropsychomotor delay. Ophthalmological examination revealed bilateral nystagmus, microphthalmia, posterior subcapsular cataratacts, extensive chorioretinal dysplasia, optic nerve aplasia, persistent fetal vasculature, and absent retinal vessels. RESULTS: Magnetic resonance revealed pachymicrogyria and discrete atrophy of vermis cerebelosum and confirmed optic nerve hypoplasia. CONCLUSIONS: The developmental alterations observed in the retina of this patient could be analogous to central nervous system anomalies, reflecting a reduction in neural population. Ophthalmic examination of children with microcephaly is warranted.

[Retinal imaging in hereditary chorioretinal dystrophies]. / Imagistica in distrofii corio-retiniene ereditare.

The paper presents retinal imaging (color and red-free photografs, fluorescein angiograms and optical coherence tomography) of the most common hereditary chorioretinal dystrophies: retinitis pigmentosa, Stargardt's disease, choroideremia, cone dystrophy vitteliform dystrophy. Retinal imaging has an important role in the diagnosis and the follow-up of these diseases, but genetic investigations are frequently necessary.