Showing papers in "Ophthalmic Genetics in 2004"

Rab escort protein 1 (REP1) in intracellular traffic: a functional and pathophysiological overview.

Abstract: The intracellular distribution of proteins, compartments, substrates, and products is an active process called intracellular traffic. Control of intracellular traffic is established by small GTP-binding proteins (Rab proteins). Rab proteins are modified by geranyl-geranyl moieties necessary for membrane association and target-protein recognition. Geranyl-geranyl groups are transferred to Rab proteins by geranyl-geranyl transferase 2 (GGTase2). GGTase2 requires Rab escort protein 1 (REP1) to bind Rab proteins. REP1null mutations underlie an X-linked retinal degeneration called choroideremia (CHM). This review summarizes the current biochemical and clinical knowledge on REP1 and CHM.

Color vision testing

Abstract: The science of color vision testing has evolved since its inception in the late 1700s. Since then, the rudimentary technique of comparing color names has been replaced by more sophisticated methods...

Leber congenital amaurosis: a genetic paradigm.

Abstract: Leber congenital amaurosis (LCA; estimated prevalence 1 : 50,000-100,000) is an early-onset inherited cause of childhood blindness characterized by a severe retinal dystrophy immediately after birth. Variants in at least six genes, AIPL1, CRB1, CRX, GUCY2D, RPE65, and RPGRIP1, have been associated with a diagnosis consistent with LCA or early-onset retinitis pigmentosa and together account for less than 50% of all LCA cases. Genetically heterogeneous inheritance has complicated the molecular analysis of LCA cases, especially sporadic ones where conventional methods are of limited value. Until recently, the management of patients with LCA relied mainly on clinical examination, electrophysiology, and other ancillary tests. Genotyping, i.e., determining the exact genetic defect causing LCA in each specific case, was not routinely performed since the comprehensive screening of six genes by SSCP and/or direct sequencing is relatively inefficient and cost-prohibitive. Patients, therefore, were often left with no specific information on their disease status. Recent advances in genotyping technologies have allowed the introduction of comprehensive and affordable screening procedures to determine causal genetic variation, resulting in precise molecular diagnosis, more accurate visual prognosis, and suggestions towards treatment options.

Association of EFEMP1 With Malattia Leventinese and Age-Related Macular Degeneration: A Mini-Review

Abstract: Malattia leventinese (ML) or Doyne honeycomb retinal dystrophy (DHRD) was the first clinically and histopathologically described Mendelian maculopathy. The gene responsible for ML/DHRD, EFEMPI (fibulin-3/SI-5/FBNL) encodes a member of the fibulin family, a newly recognized family of extracellular matrix proteins. EFEMPImutations have not been found in age-related macular degeneration (AMD) patients despite the close phenotypic similarities between ML/DHRD and AMD. This non-correlating genotype/phenotype relationship between inherited and age-related conditions is typical for common age-related diseases. Biochemical pathways delineated in other diseases indicate that the gene associated with the inherited condition is nonetheless critical in age-related forms. This review summarizes current knowledge relating to ML/DHRD and EFEMPI,with discussion of why EFEMPI mutations are absent in AMD and how EFEMPI may be involved in the pathogenesis of ML/DHRD and AMD.

Molecular basis of Peters anomaly in Saudi Arabia.

Abstract: Peters anomaly (PA) and primary congenital glaucoma (PCG) are genetically and phenotypically distinct conditions. Mutations in cytochrome P4501B1 (CYP1B1) are the most common cause of PCG in Saudi Arabia. Recent evidence suggests that there may be common genetic factors to these conditions. To determine the molecular basis of PA, 11 study subjects with PA from 10 Saudi Arabian families were recruited. Experienced ophthalmologists examined all affected subjects and most of their available unaffected relatives. The diagnosis of PA was confirmed by pathological examination of excised corneal buttons in seven subjects. The coding exons of FOXC1, PITX2, and PAX6 were screened and those of CYP1B1 and FOXE3 sequenced. Homozygous CYP1B1 mutations were identified in six individuals in five families. Five individuals were homozygous for G61E and one was homozygous for 143del10. No mutations were identified in FOXC1, PITX2, PAX6, or FOXE3. The clinical or pathologic phenotype of the subjects with CYP1B1 mutations wa...

Activity of topotecan in retinoblastoma

Abstract: Purpose: To report our experience with topotecan in children with relapsed/refractory metastatic and intraocular retinoblastoma. Patients and methods: Topotecan was administered intravenously as a 30-min infusion at a dose of 2mg/m 2 /d for five consecutive days and repeated after three weeks. If obvious progression was detected by physical examination in patients with overt extraocular disease or if progressive disease was noted after fundoscopic examination in patients with intraocular disease, a second cycle was not administered. Response was evaluated at Week 6. Results: Nine patients (6 extraocular, 3 intraocular) were treated from November 1998 to March 2002. A total of 16 cycles were administered. In patients with extraocular disease, there were three partial responses, two cases of stable disease, and one case of progressive disease. Two patients with relapsed/resistant intraocular disease had partial response, allowing local therapy to be performed, and the third patient had progressive disease. ...

Evaluation of the ARMD1 locus on 1q25-31 in patients with age-related maculopathy: genetic variation in laminin genes and in exon 104 of HEMICENTIN-1.

Abstract: The age-related maculopathy (ARM) genetics program at Columbia University utilizes comprehensive genetic analysis of candidate genes in large case-control studies to determine genotypes associated with the ARM complex trait. Genes encoding laminins, a class of extracellular matrix proteins, represent attractive candidates for two reasons. First, the presence of laminins in the basal lamina of the retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris suggests a possible role in the pathophysiology of ARM. Second, three laminin genes, LAMC1, LAMC2, and LAMB3, are located in the 1q25–31 region, within the previously mapped ARMD1 locus. The entire open reading frame of the three laminin genes was screened for variants by denaturing high-performance liquid chromatography (DHPLC) and direct sequencing in at least 92, and up to 368 ARM patients and matched unaffected controls. Sixty-nine sequence variants were detected in the 69 exons of the LAMC1, LAMC2, and LAMB3 genes. Screening of exon 104...

Autosomal dominant familial exudative vitreoretinopathy in two Japanese families with FZD4mutations (H69Y and C181R)

Abstract: Background:Familial exudative vitreoretinopathy (FEVR) is a hereditary disorder characterized by impaired vascularization of parts of the peripheral retina. Autosomal dominant FEVR (adFEVR), a major form of FEVR and assigned to chromosome 11q13–23 (EVR1) locus, is caused by deletion mutations in the C-terminal region of the frizzled-4 (FZD4) gene. This paper describes the clinical phenotype of adFEVR in two Japanese families with two different mutations in the FZD4gene. Methods:We encountered three Japanese patients with adFEVR and studied them using mutation analysis of the FZD4gene with PCR, sequencing, and a restriction enzyme digestion. Results:Two previously unreported missense mutations, p.H69Y and p.C181R, were identified in the N-terminal extracellular region of two of the patients. This region was highly conserved among other vertebrate species and FZD family members, unlike the C-terminal region. Co-segregation analysis revealed that all affected individuals carried one of these mutations, while...

Cytochrome P4501B1 mutations cause only part of primary congenital glaucoma in Ecuador

Abstract: Purpose: To determine the role of cytochrome P4501B1 ( CYP1B1 ) mutations in causing primary congenital glaucoma (PCG) in a cohort of Native Americans from Quito, Ecuador. Materials and methods: Seventeen patients with PCG from 15 Native American families were recruited from the Ophthalmology Clinic at Hospital Metropolitano, Quito, Ecuador. Experienced ophthalmologists examined all affected study subjects. Purified DNA was prepared from peripheral blood samples and CYP1B1 coding exons (exons 2 and 3) were amplified and sequenced. Southern blot was performed only on those affected patients who showed no mutations in the CYP1B1 coding exons. Results: The molecular basis of PCG in two families was determined: two novel mutations (a deletion and a point mutation) and one novel polymorphism in CYP1B1 were identified in addition to a previously described single amino acid substitution. Southern blot analyses on whole genomic DNA from affected individuals in whom no mutations were identified by the direct PCR/s...

Ocular findings in ichthyosis follicularis-alopecia-photophobia (IFAP) syndrome.

Abstract: Purpose:To report the ocular findings in two siblings with IFAP and their mother and to review the natural course of the keratopathy of this disease. Methods:Clinical ophthalmological examination of all patients and fundus photography of the carrier mother were performed. Results:Both affected male children had severe photophobia, total superficial and deep corneal vascularization, and reduction of vision to counting fingers. The mother had tortuous retinal vessels. Conclusions:Males with IFAP have an inexorable progression of corneal vascularization and loss of vision. Retinal vascular tortuosity may be another clinical sign of carrier status in females.

A novel KERAmutation associated with autosomal recessive cornea plana

Abstract: Purpose:To report a novel KERAmutation associated with autosomal recessive cornea plana in members of a nuclear family and to describe their ophthalmic phenotypes Methods:Ophthalmic examination, biometry, and direct sequencing of KERA Results:Five of the 6 siblings were affected and had small flat corneas, variable anterior chamber depths, and short axial lengths The remaining brother and the 2 parents had normal ophthalmic examinations Genetic testing revealed a novel homozygous nonsense mutation in exon 3 [937C>T] in the clinically affected individuals The clinically unaffected parents were confirmed as carriers The clinically unaffected sibling had no KERAmutation This mutation leads to replacement of an arginine by a stop codon at position 313 of keratocan protein Conclusions:This novel point mutation in KERAis the fourth thus far described The ocular phenotype is characteristic of autosomal recessive cornea plana

Clinical relevance of optineurin sequence alterations in Japanese glaucoma patients

Abstract: Purpose:To study the clinical relevance of sequence alterations in the optineurin gene (OPTN) among Japanese patients with open-angle glaucoma, including both primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). Methods:Genomic DNA was isolated from 83 patients with open-angle glaucoma (55 with POAG and 28 with NTG) and 58 control subjects. The 13 exons of OPTN corresponding to the coding region were amplified by polymerase chain reaction and directly sequenced. Clinical factors were compared between glaucoma patients with and without a certain nucleotide change. Results:The reported heterozygous mutations, c.458G > A(Glu50Lys) in exon 4 and c.691_692insAG in exon 6, were not found in any glaucoma patients or control subjects. The reported c.603T > A(Met98Lys) in exon 5 was significantly more prevalent in the POAG (8/55, 14.5%, p = 0.0147) and NTG (4/28, 14.2%, p = 0.0369) patients, and even in both the POAG and NTG patients combined (12/83, 14.4%, p = 0.0149, Fisher exact probability tes...

Mutation analysis of KIF21A in congenital fibrosis of the extraocular muscles (CFEOM) patients

Abstract: Purpose: CFEOM type 1 refers to a group of congenital eye movement disorders that is characterized by nonprogressive ophthalmoplegia affecting all the extraocular muscles Individuals with the classic form of CFEOM are born with bilateral ptosis, infraducted eyes, and impossibility to raise their eyes above midline This phenotype is often inherited as an autosomal dominant trait CFEOM1 maps to the FEOM1 locus on chromosome 12 and is the consequence of mutations in the KIF21A gene We analyzed three families and one sproradic case for potential genetic heterogeneity Methods: Blood samples were collected from members of three families (Swiss, Turkish, and French origin) and one sporadic case (Iranian origin) In families, haplotype was tested for linkage to the autosomal dominant CFEOM1 locus on chromosome 12 Linkage studies were conducted using 2 polymorphic DNA microsatellite markers, D12S331 and D12S1048 Mutation analysis was performed by PCR amplification and bidirectional direct sequencing Result

A novel mutation in the PITX2 gene in a family with Axenfeld-Rieger syndrome.

Abstract: Purpose: To determine the underlying genetic cause of Axenfeld-Rieger syndrome (ARS) in a three-generation family. Introduction: ARS is a multisystem, autosomal dominant disorder characterized by specific ocular and non-ocular anomalies sometimes caused by mutations in the transcription factor gene, PITX2 . Methods: The three coding exons of the PITX2 gene, i.e., exons 2, 3, and 4, in affected and unaffected subjects were amplified by polymerase chain reaction (PCR) and sequenced. The PCR products of exon 4 were subcloned and sequenced to confirm the nature of the mutation. Results: A deletion of thymine (T) 1261 was identified, creating a frameshift mutation in codon 227. This change is predicted to create 11 novel amino acids downstream, followed by premature truncation of the protein. Conclusions: This mutation highlights the functional importance of a conserved 14-amino acid sequence at the C-terminus of the protein thought to be important in repressing DNA binding and in protein-protein interactions.

A novel RDS/peripherin gene mutation associated with diverse macular phenotypes

Abstract: Pattern dystrophy is a heterogeneous group of retinal dystrophies of which butterfly-shaped pattern dystrophy (BPD) and adult-onset foveomacular dystrophy (AOFMD) are the two most common forms. BPD is characterized by a butterfly-shaped, irregular, depigmented lesion at the level of the retinal pigment epithelium. In contrast, AOFMD is characterized by the presence of slightly elevated, symmetric, solitary, round to oval, yellow lesions at the level of the retinal pigment epithelium. We identified three independent kindreds with pattern dystrophy, one with four patients affected with BPD and the other two with 14 affected patients with AOFMD. We performed complete ophthalmic examination, fluorescein angiography, linkage mapping, and mutational screening in the RDS/peripherin gene in the affected patients. Patients affected with BPD had a best-corrected vision of 20/20 to 20/25, whereas vision in the eyes of patients with AOFMD ranged from 20/20 to 20/400. In all three kindreds, sequence analysis identified an A-to-G change at nucleotide position 422 of the RDS/peripherin gene, predicting a novel Tyr-141-Cys substitution. A haplotype analysis revealed that these three kindreds shared an identical disease haplotype at the RDS/peripherin locus, indicating that the mutation reflects a founder effect. The sequence change that segregated with the disease phenotype was not observed in 200 control chromosomes. Our results identified a novel mutation in the RDS/ peripherin gene that can cause diverse macular phenotypes. Genetic and clinical investigation of pattern dystrophy may provide useful diagnostic tools and new treatment strategies for this disorder.

Oculodentodigital dysplasia: study of ophthalmological and clinical manifestations in three boys with probably autosomal recessive inheritance.

Abstract: Oculodentodigital dysplasia (ODDD) is a rare inherited disorder affecting the development of the face, eyes, teeth, and limbs. The majority of cases of ODDD are inherited as an autosomal dominant condition. There are few reports of probable autosomal recessive transmission. Affected patients exhibit a distinctive physiognomy with a narrow nose, hypoplastic alae nasi, and anteverted nostrils, bilateral microphthalmos, and microcornea. Sometimes iris anomalies and secondary glaucoma are present. There are malformations of the distal extremities such as syndactyly. In addition, there are defects in the dental enamel with hypoplasia and yellow discoloration of the teeth. Less common features include hypotrichosis, intracranial calcifications, and conductive deafness secondary to recurrent otitis media. We describe three brothers with ODDD. Their parents are first cousins and present no features of ODDD. These data are in favor of autosomal recessive inheritance and suggest genetic heterogeneity for this entity.

Fluorine-18 fluorodeoxyglucose positron emission tomography (PET) to detect vital retinoblastoma in the eye: Preliminary experience

Abstract: Background/aims: To report our first experience with FDG-PET in the detection of vital retinoblastoma. Methods: Four newly diagnosed retinoblastoma patients, two treated retinoblastoma patients, and four control patients were enrolled in this pilot study. F18-FDG uptake was assessed in the light of clinical and histopathological features. Results: PET discriminated between new patients and controls, although tumor uptake varied widely. PET added no useful information with regard to possible vital tissue in tumor scars in the eye of the two treated retinoblastoma patients. Moreover, PET findings did not correlate with clinical or histopathological features. Conclusion: Based on this small pilot study, F18-PET shows little promise in the detection of retinoblastoma. More research on other radiofarmacons is recommended.

Mutation analysis of the KIF21A gene in an Indian family with CFEOM1: implication of CpG methylation for most frequent mutations.

Abstract: Purpose: To carry out the mutation analysis of the KIF21A gene in a four-generation Indian family affected with CFEOM1 and to find out the molecular basis of the most frequent mutations c.2860C>T and c.2861G>A in exon 21 of the KIF21A gene. Methods: Mutational analysis was carried out by direct automated sequencing of the PCR products from exons 8, 20, and 21 of the KIF21A gene. Allele specific oligo hybridization analysis was carried out to study the segregation of the mutation within the family. Methylation status of the mutated CpG dinucleotide in exon 21 was detected using bisulfite genomic sequencing technique on genomic DNA isolated from blood and sperms. Results: We found a previously reported missense mutation c.2860C>T (p.954R>W) in exon 21 of the KIF21A gene in our family. This mutation was found in a CpG dinucleotide. Bisulfite genomic sequencing revealed that all the CpG dinucleotides in exon 21 including the one which harbored the two most frequent mutations were methylated both in the genomic DNA from blood and sperms. Conclusions: CFEOM1 phenotype in our family was caused by a previously reported most frequent missense mutation, c.2860C>T. This mutation occurred at the C residue in a CpG dinucleotide, which was found to be methylated. Previous work has demonstrated that this CpG dinucleotide is a mutational hotspot in the KIF21A gene, and our finding suggests that its high mutability may result, in part, from its methylated state.

Mutations in KIF21A are responsible for CFEOM1 worldwide.

Abstract: The classification of syndromes with congenital limitation of eye movements from cranial nerve dysgenesis continues to evolve. Normal extraocular muscle (EOM) function depends on normal cranial nuclear motoneuron formation from neuronal precursors, normal axonal pathfinding from the cranial nuclei to developing EOMs, and the establishment and maintenance of normal connections between mature neurons and their target cells. The term ‘congenital cranial dysinnervation disorders’ (CCDDs) has been coined to encompass congenital disorders that result from aberrant innervation of the ocular and facial musculature. These include Duane retraction syndrome (DRS), the several types of congenital fibrosis of the extraocular muscles (CFEOM), Möbius syndrome, and congenital horizontal gaze palsy with progressive scoliosis (HGPPS). Other conditions with isolated motor, sensory, or combination of cranial nerve abnormalities could also be grouped under this rubric. Abnormalities of cranial nerve development have been clearly demonstrated in some of these conditions using magnetic resonance imaging or postmortem examination. Mutations in genes important in motoneuronal nuclear development or in the integrity and normal function of cranial nerves have been demonstrated to cause some of these disorders. These genes include PHOX2A (ARIX), SALL4, KIF21A, and ROBO3. Mutations in these genes result in isolated abnormalities of ocular motility, or in complex syndromes in which cranial nerve dysfunction is accompanied by skeletal or other systemic abnormalities. There appear to be three main mechanisms through which congenital cranial nerve dysfunction occurs in patients with congenital ocular movement disorders. The first involves failure of the cranial nerve nuclei to develop normally and their motoneuron component cells to

A missense mutation in GUCY2D acts as a genetic modifier in RPE65-related Leber Congenital Amaurosis.

Abstract: Leber congenital amaurosis (LCA) is a clinically and genetically heterogeneous severe retinal dystrophy presenting in infancy. To explain the phenotypical variability observed in two affected siblings of a consanguineous pedigree diagnosed with LCA and establish a genotype-phenotype correlation, we screened GUCY2D, RPE65, CRX, AIPL1, and RPGRIP1for mutations. The more severely affected sibling carried a heterozygous missense mutation in the GUCY2Dgene (Ile539Val), which did not segregate with the disease phenotype. Subsequently, a homozygous nonsense mutation (Glu102STOP) in the RPE65gene was identified in both affected siblings, thus identifying the causative gene. This data provides evidence for the presence of genetic modulation in LCA. It appears that the heterozygous GUCY2D mutation further disrupts the already compromised photoreceptor function resulting in more severe retinal dysfunction in the older sibling. We suggest that the unusual phenotypic variability in these two siblings with LCA is cause...

Genetic analysis of an Indian family with members affected with juvenile-onset primary open-angle glaucoma

Abstract: Purpose: Glaucoma is the second leading cause of blindness. In India, ~1.5 million people are blind due to glaucoma. Mutations in the MYOC gene located at the GLC1A locus on chromosome 1q21–q31 have been found in patients with juvenile-onset primary open-angle glaucoma (J-POAG). The purpose of the present study was to identify the genetic cause of glaucoma in a four-generation Indian family affected with J-POAG. Methods: Peripheral blood samples were obtained from individuals for genomic DNA isolation. To determine if this family was linked to the GLC1A locus, haplotyping analysis was carried out using microsatellite markers from the GLC1A candidate region. Exon-specific primers from exon 3 of the MYOC gene were used to amplify DNA samples from individuals. Mutation analysis was carried out using PCR-SSCP and DNA sequence analyses. Results: Pedigree analysis suggested that glaucoma in this family segregated as an autosomal dominant trait. Of six patients, five had J-POAG and one had adult-onset POAG (A-POAG). Haplotype analysis suggested linkage of this family to the GLC1A locus. Mutation and sequence analyses showed a novel missense mutation, c.821C > G (p.P274R), in the C-terminal olfactomedin domain coded by exon 3 of the MYOC gene. One patient was found to be homozygous for this mutation with a severe phenotype. Conclusions: This study reports a novel missense mutation in a four-generation Indian family with all but one member affected with J-POAG. The total number of mutations described so far in the MYOC gene, including the one reported here, is 59 with a clustering of 52 mutations in exon 3.

Ocular manifestations of mosaic trisomy 22: a case report and review of the literature

Abstract: Mosaic trisomy 22 is rare, but can be compatible with prolonged life. Patients with mosaic trisomy 22 usually present with intrauterine growth retardation, mental retardation, failure to thrive, and craniofacial asymmetry. We report the case of a five-year-old boy who had a birth weight of 3.8kg and normal developmental milestones. He presented with unilateral ocular manifestations of ptosis, double elevator palsy, high myopia, and choroidal coloboma involving the macula. Cytogenetic evaluation showed a low level of trisomy 22 in peripheral blood lymphocytes (1 in 100) and in cultured fibroblasts from a conjunctival biopsy of the affected eye (1 in 60). Our case demonstrates the value of chromosomal analysis of the tissues involved rather than just karyotyping of the blood lymphocytes to detect mosaicism in patients with localised and unilateral congenital malformations.

Refinement of the X-linked cataract locus (CXN) and gene analysis for CXN and Nance-Horan syndrome (NHS).

Abstract: The X-linked congenital cataract (CXN) locus has been mapped to a 3-cM (approximately 35 Mb) interval on chromosome Xp2213, which is syntenic to the mouse cataract disease locus Xcat and encompasses the recently refined Nance-Horan syndrome (NHS) locus A positional cloning strategy has been adopted to identify the causative gene In an attempt to refine the CXN locus, seven microsatellites were analysed within 21 individuals of a CXN family Haplotypes were reconstructed confirming disease segregation with markers on Xp2213 In addition, a proximal cross-over was observed between markers S3 and S4, thereby refining the CXN disease interval by approximately 400 Kb to 32 Mb, flanked by markers DXS9902 and S4 Two known genes (RAI2 and RBBP7) and a novel gene (TL1) were screened for mutations within an affected male from the CXN family and an NHS family by direct sequencing of coding exons and intron- exon splice sites No mutations or polymorphisms were identified, therefore excluding them as disease-causative in CXN and NHS In conclusion, the CXN locus has been successfully refined and excludes PPEF1 as a candidate gene A further three candidates were excluded based on sequence analysis Future positional cloning efforts will focus on the region of overlap between CXN, Xcat, and NHS

Are Duane syndrome and infantile esotropia allelic

Abstract: Purpose:To evaluate the clinical overlap of families with Duane syndrome and infantile esotropia to determine whether the identification of genes for Duane syndrome may explain some cases of infantile esotropia. Methods:Three separate groups of patients were evaluated. 1) Families with features of infantile esotropia were identified through the Strabismus Inheritance Study Tasmania (SIST). Clinical details of participants and their families were reviewed for any cases of Duane syndrome. 2) Cases of Duane syndrome were identified through the clinical diagnostic database at the Royal Children's Hospital, Melbourne, and private ophthalmology clinics in Melbourne and Tasmania. Previous medical notes were reviewed and family history of strabismus noted. All affected individuals were invited for re-examination in cases where a positive family history of strabismus was reported; siblings, parents, and other family members, where appropriate, were invited to be examined for signs of Duane syndrome or infantile es...

Fundus features of a case of neurocutaneous melanosis

Abstract: A 5-year-old girl with giant cutaneous congenital melanocytic nevi was examined because of right esotropia. She had multiple uveal coloboma-like lesions of various sizes and irregular areas of retinal pigment epithelial alterations in the right fundus. Magnetic resonance imaging studies demonstrated right-sided ventriculomegaly, right intraventricular presumed dysplastic neuroectodermal tumor, and right-sided cortical migration anomaly. The clearly lateralized ocular, cutaneous, and central nervous system findings in this patient may point towards a probable common underlying pathogenetic mechanism involving the neural crest cells at the center stage. These findings also help to strengthen the view that neurocutaneous melanosis may represent a rare form of phakomatosis.

A second primary tumor in a patient with retinoma.

Abstract: Aim: To evaluate the frequency of the co-occurrence of a retinoma and another primary tumor. Method: Presentation of a case report and review of the literature. Results: A cutaneous melanoma was observed in a 52-year-old man, who was known to have two retinomas in the right eye. Five other cases were found in a review of the literature, suggesting the possibility of an increased risk of developing a second primary tumor in patients with retinoma. The occurrence of cutaneous melanoma as a second primary tumor after retinoma and/or retinoblastoma is discussed. Conclusion: There might be an increased risk for patients with retinoma to develop another primary tumor, necessitating regular follow-up of these patients.

Neurofibromatosis type 1 associated with central nervous system lymphoma.

Abstract: Purpose: To report the occurrence of central nervous system (CNS) lymphoma in a patients with neurofibromatosis type 1 (NF1). Design: Interventional case report. Methods: A 47-year-old male with a ...

Lack of activity of oral etoposide for relapsed intraocular retinoblastoma.

Abstract: Background: Intravenous etoposide is widely used in multiagent chemotherapy regimens for intraocular retinoblastoma despite the lack of phase II data documenting its efficacy. Because oral etoposide has been found to be highly effective in patients with relapsed medulloblastoma and neuroblastoma who had previously received intravenous etoposide, we investigated its use for intraocular retinoblastoma. Procedure: A pilot trial of oral etoposide (50mg/m 2 /day for 21 days) in five children (6 eyes) with relapsed refractory intraocular retinoblastoma was performed. All had previously received chemotherapy, including intravenous etoposide in four patients, and all had received radiation therapy. Three patients (3 eyes) had vitreous seeds. Response was evaluated after one cycle. Results: No serious acute toxicity was encountered, and no responses were noted. Four patients (5 eyes) had progressive disease. Stable disease was noted in one eye without vitreous disease. One patient developed secondary acute myeloid...

Ontogenetic development of visual acuity over the first three postnatal years

Abstract: Introduction Spatial vision is arguably the most important of all visual functions, and measurement of visual acuity, which represents the limits of a patient’s spatial resolution, is by far the internationally accepted index. Clinically, tests of visual acuity (e.g., Snellen, log MAR, and Illiterate E charts) are important, both for the diagnosis of ocular and CNS pathology as well as for monitoring the functional success of treatment and recovery. Measurement of visual acuity in adults and older children is performed easily, and repeatability is excellent. However, for both preverbal (infant) and nonverbal (neurologically-impaired) patients, communication and attentional limitations render traditional clinical tools unuseable. Assessment of functional vision in infants is critical for two reasons. First, although routine structural examination (including ophthalmoscopy, ocular motility/alignment) can reveal the presence of patent ocular abnormalities, more subtle aberrations such as a slight strabismus or opacity, anisometropia, unbalanced monocular output, significant refractive error, or altered neuro-ophthalmic development, are not detected easily in this population.These infantile conditions, all of which can be revealed by sub-normal visual acuity, are significant as they are the direct precursors of untreatable eye diseases in later childhood such as amblyopia or poor binocular functioning. Second, early detection and treatment of visual anomalies during the relatively brief but most significant portion of the period of visual system plasticity (roughly, the first three postnatal years) can result in substantially improved prognoses. In recent years, several tests have emerged that attempt to measure early visual acuity, primarily with the use of black-and-white squarewave grating patterns. The most well-known of these, the Teller acuity

Autosomal dominant brachydactyly, coloboma and anterior segment dysgenesis

Abstract: A three-generation family presenting with ocular developmental abnormalities, including anterior segment dysgenesis and coloboma, associated with brachydactyly and clinodactyly is presented. Several conditions incorporating ocular and bony limb abnormalities have been described. However, we believe that this family manifests a previously undescribed syndrome due to autosomal dominant or possibly x-linked inheritance with variable expression.