Retinal Mottling Research Articles

Seizures and Cardiomyopathy in a Patient with Pallister-Killian Syndrome due to Hexasomy 12p Mosaicism

Pallister-Killian syndrome (PKS) is a rare disorder presenting with developmental delay, numerous dysmorphic features, and skin pigmentation anomalies. It is caused by mosaic tetrasomy of the short arm of chromosome 12. In most instances, tetrasomy is due to a supernumerary isochromosome i(12)(p10). Although mitotic instability is a generally accepted behavior for supernumerary chromosomes, hexasomy 12p due to a gain of an isochromosome 12p, has been hardly ever reported. We report a 10 year follow-up on a girl with 2 copies of isochromosome consisting of the short arm of chromosome 12, who has craniofacial features seen in PKS, such as sparse hair with an unusual pattern, sparse eyebrows, lacrimal duct stenosis, submucous cleft palate, Pallister lip (a relatively long philtrum continuing into the vermillion border of the upper lip), narrow palate, and wide alveolar ridges. She also has other abnormalities, including unilateral renal dysgenesis, rectovaginal fistula, pre-axial polydactyly of the right hand, severe global developmental delay, and hypotonia as well as some features suggestive of mosaicism such as bilateral asymmetry, patchy areas of rough skin, and retinal mottling. Initial cytogenetic studies from peripheral blood showed a normal female karyotype. Further cytogenetic studies on a skin biopsy showed mosaicism with 2 copies of the supernumerary isochromosome 12p.

Retinitis Pigmentosa and Bilateral Idiopathic Demyelinating Optic Neuritis in a 6-Year-Old Boy with OFD1 Gene Mutation.

To identify the cause of a sudden binocular vision decrease in patients with retinitis pigmentosa and bilateral idiopathic demyelinating optic neuritis is difficult, but early diagnosis and treatment significantly improve the prognosis. Here, we report a 6-year-old boy with a progressive binocular vision decrease in 38 days. The patient had a history of night blindness, a mottled retina without pigmentation, extinguished electroretinographic response, tritanopia, and an absent ellipsoid zone outside the macula fovea by optical coherence tomography in both eyes. His condition was diagnosed as retinitis pigmentosa (RP) with idiopathic demyelinating optic neuritis (IDON). After corticosteroid therapy, visual acuity recovered to OD: 0.5 and OS: 0.4. Genetic analysis revealed a G985S variant in the oral-facial-digital syndrome 1 gene. Ophthalmologists should pay attention to the existence of other complications in patients with RP who suffer a sudden decrease in vision. A gene survey can help clarify this diagnosis. To our knowledge, this is the first report of a patient with RP and ON, as well as genetic testing results. Nevertheless, the pathogenicity of the variant needs further confirmation.

English

INTRODUCTION: HISTORY: A 30 year old lady in her 32 weeks gestation period was referred to our ophthalmology clinic with chief complaints of diminution of vision in both eyes for 4 months duration. Her medical history was suggestive of uncontrolled hypertension. On Ophthalmic evaluation she had best corrected visual acuity of 20/200 in both eyes with normal color vision. Her pupils were bilaterally equal in size and normally reacting to light. The intraocular pressure was within normal range and anterior segment evaluation was within normal limits. Dilated fundus evaluation revealed only arterio-venous crossing changes, mottled retina and resolving hard exudates in both eyes [Fig 1a, & 1b]. The fundus picture could not explain the severity of vision loss in the patient which prompted us for further workup.

Occurrence and pattern of ocular disease in children with cholestatic disorders

To describe visual function and ocular manifestations in patients with onset of cholestasis during the neonatal period. Patients with neonatal cholestasis, either transitory or chronic, who came for assessment to our tertiary referral centre were included in a cross-sectional study and underwent ophthalmological examinations including fundus photography. A total of 57 patients (24 girls and 33 boys), aged 0.4-18.0 years, were included. Of these, 28 patients had biliary atresia, 11 had Alagille's syndrome, five had progressive familiar intrahepatic cholestasis and nine had different disorders such as pituitary insufficiency, alpha-1-antitrypsin deficiency, mitochondriopathy, congenital infections or cholestasis caused by unknown reasons. Visual dysfunction and/or one or several ocular manifestations occurred in 39 out of 57 patients. Major ocular malformations occurred in five patients. Out of three patients with biliary atresia, one patient had severe visual impairment caused by microphthalmia and chorioretinal coloboma, one patient with Cat Eye syndrome had bilateral uveochorioretinal coloboma and one patient had Rieger's anomaly. Two patients, both with pituitary deficiency and transient cholestasis, had severe unilateral visual impairment caused by optic nerve hypoplasia. The majority (68%) of the patients with cholestasis had ocular manifestations. Although the severity of ocular complications varied with diagnosis, and was most apparent among patients with biliary atresia or pituitary deficiency, no conclusion can be drawn regarding the connections between these conditions from the present study. Nevertheless, ocular assessment is important for diagnostic purposes and for early intervention in patients with cholestasis.

Ocular characteristics in 10 children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: a cross-sectional study with long-term follow-up

Ocular characteristics in 10 children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: a cross-sectional study with long-term follow-up

Two mouse retinal degenerations caused by missense mutations in the β-subunit of rod cGMP phosphodiesterase gene

We report the chromosomal localization, mutant gene identification, ophthalmic appearance, histology, and functional analysis of two new hereditary mouse models of retinal degeneration not having the Pde6b rd1 (“ r”, “ rd”, or “rodless”) mutation. One strain harbors an autosomal recessive mutation that maps to mouse chromosome 5. Sequence analysis showed that the retinal degeneration is caused by a missense point mutation in exon 13 of the β-subunit of the rod cGMP phosphodiesterase (β-PDE) gene ( Pde6b). The gene symbol for this strain was set as Pde6b rd10 , abbreviated rd10 hereafter. Mice homozygous for the rd10 mutation showed histological changes at postnatal day 16 (P16) of age and sclerotic retinal vessels at four weeks of age, consistent with retinal degeneration. Retinal sections were highly positive for TUNEL and activated caspase-3 immunoreactivity, specifically in the outer nuclear layer (ONL). ERGs were never normal, but rod and cone ERG a- and b-waves were easily measured at P18 and steadily declined over 90% by two months of age. Protein extracts from rd10 retinas were positive for β-PDE immunoreactivity starting at about the same time as wild-type (P10), though signal averaged less than 40% of wild-type. Interestingly, rearing rd10 mice in total darkness delayed degeneration for at least a week, after which morphological and functional loss progressed irregularly. With the second strain, a complementation test with rd1 mice revealed that the retinal degeneration phenotype observed represents a possible new allele of Pde6b. Sequencing demonstrated a missense point mutation in exon 16 of the β-subunit of rod phosphodiesterase gene, different from the point mutations in rd1 and rd10. The gene symbol for this strain was set as Pde6b nmf137 , abbreviated nmf137 hereafter. Mice homozygous for this mutation showed retinal degeneration with a mottled retina and white retinal vessels at three weeks of age. The exon 13 missense mutation ( rd10) is the first known occurrence of a second mutant allele spontaneously arising in the Pde6b gene in mice and may provide a model for studying the pathogenesis of autosomal recessive retinitis pigmentosa (arRP) in humans. It may also provide a better model for experimental pharmaceutical-based therapy for RP because of its later onset and milder retinal degeneration than rd1 and nmf137.

MORM syndrome (mental retardation, truncal obesity, retinal dystrophy and micropenis), a new autosomal recessive disorder, links to 9q34

A consanguineous pedigree is described where 14 individuals are affected with a novel autosomal recessive disorder, which causes static moderate mental retardation, truncal obesity, a congenital nonprogressive retinal dystrophy and micropenis in males. We have tentatively named this condition MORM syndrome. It shows similarities to Bardet-Biedl syndrome and Cohen syndrome, but can be distinguished by clinical features; the age of onset and nonprogressive nature of the visual impairment, the lack of characteristic facies, skin or gingival infection, microcephaly, 'mottled retina', polydactyly and small penis without testicular anomalies. Furthermore, linkage to the known Bardet-Biedl (BBS1-8) and Cohen syndrome loci was excluded. Autozygosity mapping identified a single homozygous subtelomeric region shared by all affecteds on chromosome 9q34.3, with a maximum LOD score of 5.64. We believe this to be the first example of the identification of a subtelomeric recessive locus by autozygosity mapping.

Cytomegalovirus retinitis in a patient with non-Hodgkins lymphoma: A diagnostic dilemma.

Patients with lymphoma can rarely develop cytomegalovirus (CMV) retinitis. Clinically it is difficult to distinguish from intraocular lymphoma. Also, in such cases the CD4+ count may be high. The authors report a rare case of bilateral CMV retinitis in a patient with non-Hodgkins lymphoma with high CD4+ counts. Observational case report with review of literature. CMV retinitis was clinically suspected due to the presence of large areas of retinal necrosis and hemorrhages in one eye and a demarcation line with white mottled retina in the other eye. Other differential diagnoses considered were intraocular lymphomatous infiltration and acute retinal necrosis due to herpes group of viruses. The diagnosis of CMV retinitis was confirmed by polymerase chain reaction performed on vitreous sample. CMV retinitis can develop in cases of lymphoma despite high CD4+ counts. An early diagnosis can be established by performing PCR on vitreous biopsy. (Eur J Ophthalmol 2005; 15: #-7).

Cytomegalovirus Retinitis in a Patient with Non-Hodgkin's Lymphoma: A Diagnostic Dilemma

Patients with lymphoma can rarely develop cytomegalovirus (CMV) retinitis. Clinically it is difficult to distinguish from intraocular lymphoma. Also, in such cases the CD4+ count may be high. The authors report a rare case of bilateral CMV retinitis in a patient with non-Hodgkin's lymphoma with high CD4+ counts. Observational case report with review of literature. CMV retinitis was clinically suspected due to the presence of large areas of retinal necrosis and hemorrhages in one eye and a demarcation line with white mottled retina in the other eye. Other differential diagnoses considered were intraocular lymphomatous infiltration and acute retinal necrosis due to herpes group of viruses. The diagnosis of CMV retinitis was confirmed by polymerase chain reaction performed on vitreous sample. CMV retinitis can develop in cases of lymphoma despite high CD4+ counts. An early diagnosis can be established by performing PCR on vitreous biopsy.

Case of acute zonal occult outer retinopathy resembling retrobulbar optic neuropathy

We report a case of acute zonal occult outer retinopathy (AZOOR) with a central scotoma and normal fundus. A 17-year-old man presented with reduced vision in his right eye.A relative afferent pupillary defect was not present, and his fundi were normal. He had a central scotoma in the right eye, but the left eye was normal. Central flicker fusion and color vision were normal in both eyes. Fluorescein angiography showed a somewhat mottled retina in the midperiphery of the right eye. The visually evoked potentials were reduced bilaterally. The a- and b-waves of the photopic ERGs and the amplitude of the flicker ERGs were reduced. In addition, the multifocal electroretinograms (mERGs) were reduced. A diagnosis of AZOOR was made. Electrophysiological studies were helpful in making a diagnosis of AZOOR in this case.

The Cohen syndrome: Does mottled retina separate a finnish and a jewish type?

A new familial cases of the Cohen syndrome in two brothers of one-half second-cousin parents is reported. Typical clinical manifestations of the syndrome; i.e., mental deficiency, hypotonia, characteristic facial appearance, long, narrow hands and feet with elongated fingers, and mottled retinae were present in both patients. Both patients also had leukopenia. Clinical manifestations of the Cohen syndrome in patients are highly variable, and mottled retina has been observed in 22 of 87 patients (25%). However, an association of mottled retina in patients with the Cohen syndrome is likely to be related to the families and ethnic groups. Among 19 familial cases, mottled retina was observed in all affected sibs from five families, but in 13 families none of the affected sibs had the mottled retina. All Finnish patients had the mottled retina, but this was noted in only one of 39 Jewish patients. Based on these data, we hypothesize that two alleles at the gene locus for the Cohen syndrome exhibit different clinical manifestations: one is a Finnish type with mottled retina, and the other is a Jewish type without retinal anomalies.