Mutation in MPDZ causes severe congenital hydrocephalus.

BACKGROUND: Congenital hydrocephalus is an important birth defect that is heterogeneous in aetiology and clinical presentation. Although genetics is believed to play an important role in the aetiology of non-syndromic congenital hydrocephalus, the overwhelming majority of cases lack mutations in L1CAM, the only disease gene identified to date. The purpose of this study is to identify a novel genetic cause of congenital hydrocephalus. METHODS: Families with congenital hydrocephalus were phenotyped clinically and, in one family, autoyzogisty mapping and linkage analysis were pursued. Sequencing of the genes within the candidate locus was followed by targeted sequencing of the likely candidate gene in two other families. RESULTS: We have identified a family in which severe congenital hydrocephalus of the communicating type follows an autosomal recessive mode of inheritance. Linkage analysis and autozygosity mapping narrowed the critical interval to 6.9 Mb on 9p24.1-p22.3 spanning just six genes. Direct sequencing of these genes revealed a truncating mutation in MPDZ, encoding a tight junction protein. Remarkably, we have also identified the same founder mutation in a stillbirth with massive congenital hydrocephalus from another family. CONCLUSIONS: Our data strongly support the candidacy of MPDZ as a novel congenital hydrocephalus disease gene.

Efficacy of topical cysteamine in nephropathic cystinosis.

PURPOSE: The aim of this study is to evaluate the efficacy of topical cysteamine 0.55% eye drops in the treatment of corneal cystine crystal deposits in patients with nephropathic cystinosis. METHODS: Thirty-two patients with nephropathic cystinosis were prospectively included in the study. Patients with corneal cystinosis were treated with topical cysteamine 0.55% eye drops. They were examined before treatment, on each monthly visit and after treatment at the last follow-up. Photophobia was classified as grade 0 (none) for no photophobia, grade 1 (mild) for photophobia in bright light, grade 2 (moderate) for photophobia in room light and grade 3 (severe) for photophobia in dim light. Corneal cystine crystals were graded as grade 0=none, grade 1=1-10 crystals/mm2, grade 2=11-50 crystals/mm2, grade 3=more than 50 crystals/mm2. The main outcome measure was evaluation of photophobia and resolution of corneal cystine crystals. RESULTS: There were 13 male and 19 female patients. The mean age was 8 years with an age range of 8 months to 19 years. The mean follow-up period was 4.1 years with a range of 2-8 years. Improvement of photophobia was not clinically significant in symptomatic patients. Patients displayed statistically significant worsening of corneal cystine deposits during the follow-up period. CONCLUSIONS: This study has shown that topical 0.55% cysteamine eye drops may have limited effects in decreasing the corneal cystine deposits in patients with severe forms of nephropathic cystinosis. TRIAL REGISTRATION NUMBER: NCT02766855, Results.

Ophthalmic manifestations of Sanjad-Sakati syndrome.

BACKGROUND: Sanjad-Sakati syndrome (SSS) is a rare disorder characterized by hypoparathyroidism, growth and developmental delay, and dysmorphism. The purpose of this report is to describe the ophthalmic manifestations of Sanjad-Sakati syndrome (SSS; hypoparathyroidism-mental retardation-dysmorphism syndrome, HRD) (OMIM 241410). PATIENTS: We included a total of 17 patients who were seen at two hospitals in Riyadh. METHODS: Each patient underwent a complete ophthalmologic evaluation including visual acuity assessment, orthoptic workup, slit-lamp biomicroscopy, intraocular pressure measurement, cycloplegic retinoscopy, funduscopy, corneal diameter, and axial length measurement. RESULTS: All 17 (100%) of the patients had normal visual acuity. All patients had microphthalmia with normal intraocular pressure. Eight (47%) of the patients had esotropia and four (23%) had exotropia. Ophthalmoscopy revealed tortuous retinal blood vessels in all patients. Hyperopic astigmatism was present in 16 (94%) patients. CONCLUSION: Patients with SSS display a variety of ocular findings including errors of refraction, strabismus, and retinal vascular tortuousity.

Ocular manifestations of systemic lupus erythematosus in children.

OBJECTIVE: To determine the prevalence and spectrum of ocular manifestations in children with systemic lupus erythematosus (SLE) and to examine the correlation of the ocular manifestations with disease activity, other organ involvement and the presence of circulating autoantibodies. METHODS: In this cross-sectional study, we performed at King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia from June 2000 to November 2002, a comprehensive evaluation including detailed eye examination, measuring circulating autoantibodies (antinuclear, antiphospholipid antibodies) and calculation of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). RESULTS: Fifty-two consecutive children (45 females) with SLE completed the evaluation. The mean age of the patients was 11.3 years and the mean SLEDAI was 9.5. Thirty patients (57.7%) had the disease for more than one year. Eighteen patients (34.6%) had ocular manifestations. Seven patients had abnormal Schirmer s test (2 bilateral, 5 unilateral). Five patients had (4 unilateral, one bilateral) retinal vascular lesions. One patient had bilateral iridocyclitis. Three patients had unilateral optic neuropathy and 11 patients had visual field defects (4 bilateral, 7 unilateral). Fisher exact test revealed positive correlation between optic neuropathy and central nervous system (CNS) involvement (p<0.002). There was no correlation among other variables; probably due to the sample size. CONCLUSION: Ocular manifestations including sight threatening complications are not rare in children with SLE. Optic neuropathy has strong prediction for CNS lupus.

Ocular manifestations in chronic granulomatous disease in Saudi Arabia.

INTRODUCTION: Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by a genetic defect in the NADPH oxidase complex of phagocytic cells. Recent reports indicate that chorioretinal lesions are more common than previously suspected. In this study, ocular findings of CGD patients are described with particular emphasis on chorioretinal lesions as a potentially serious ocular complication of CGD. METHODS: Medical records of CGD patients attending an immunodeficiency clinic at a tertiary care center from January 2004 to December 2006 were reviewed. Patients underwent full ophthalmologic examination. Patients with chorioretinal lesions were investigated for various causes of chorioretinitis. Molecular studies for common CGD-causing genes were performed in patients with chorioretinal lesions. RESULTS: This cohort included 32 CGD patients: 14 (44%) had abnormal eye findings, 11 (34%) had anterior segment disease, and 4 (12.5%) had chorioretinal lesions. Posterior segment findings consisted of uniformly similar hypopigmented atrophic punched-out chorioretinal scars around the arcades and mid-equator sparing of the macula. One patient had exudative hemorrhagic total retinal detachment in the right eye. Two siblings with chorioretinal lesions had mutation in CYBB, an X-linked gene. Another patient carried a missense mutation in NCF2, causing autosomal-recessive disease. CONCLUSIONS: While ocular manifestation is common in CGD, chorioretinal lesions seem less frequent. However, they present potential risk of visual loss; it is recommended that patients undergo regular ophthalmologic examinations. This report provides further evidence that chorioretinal lesions occur not only in X-linked, but they can also occur in the autosomal-recessive form of CGD.

Infliximab effects compared to conventional therapy in the management of retinal vasculitis in Behçet disease.

PURPOSE: To assess the outcome of retinal vasculitis in patients with Behçet disease treated with infliximab compared to treatment with conventional therapy. DESIGN: Nonrandomized, retrospective comparative clinical study. METHODS: Patients with Behçet disease with all four major criteria were included in this study. Patients had recurrent episodes of uveitis and retinal vasculitis. Thirty-three patients (Group 1) were treated with oral prednisone, cyclosporine, and azathioprine or methotrexate for a minimum period of three months. Ten patients (Group 2) who failed to respond to conventional therapy were given infliximab at a dose of 5 mg/kg in a single intravenous infusion on day 1 and every two weeks for a total of six doses. Patients were given the same treatment during each subsequent relapse. The main outcome measures were the number of relapses, visual outcome, and ocular complications. RESULTS: The mean follow-up period was 36 months in Group 1 and 30 months in Group 2. The mean number of relapses was significantly reduced and the duration of remission was longer in the infliximab therapy group compared to conventional therapy group (P < .0001). The visual acuity at 24 months follow-up was significantly better in patients treated with infliximab (Group 2) when compared to conventional therapy (Group 1) (P = .0059). CONCLUSIONS: Patients with Behçet disease had significant decrease in inflammation, improvement of visual acuity, and reduced ocular complications following infliximab when compared to conventional therapy. The number of relapses was less in the infliximab treatment group than the conventional therapy group.