Tonic pupil in child after chicken pox.

This is a case report of a 3-year-old boy who presented with unilateral anterior uveitis and tonic pupil following varicella-zoster virus (VZV) Infection. The patient had red and irritated eyes and photophobia. Ophthalmological findings included anterior uveitis and tonic pupil accompanied by reduced vision and accommodation. An MRI of the cerebrum was normal. To ease the symptoms the patient was prescribed photophobia glasses with correction of hyperopia. Tonic pupil due to VZV infection is a rare complication, but may have long-term consequences, why patients with eye-involving VZV infection need to be examined by an ophthalmologist.

Choline transporter-like 1 deficiency causes a new type of childhood-onset neurodegeneration.

Cerebral choline metabolism is crucial for normal brain function, and its homoeostasis depends on carrier-mediated transport. Here, we report on four individuals from three families with neurodegenerative disease and homozygous frameshift mutations (Asp517Metfs*19, Ser126Metfs*8, and Lys90Metfs*18) in the SLC44A1 gene encoding choline transporter-like protein 1. Clinical features included progressive ataxia, tremor, cognitive decline, dysphagia, optic atrophy, dysarthria, as well as urinary and bowel incontinence. Brain MRI demonstrated cerebellar atrophy and leukoencephalopathy. Moreover, low signal intensity in globus pallidus with hyperintensive streaking and low signal intensity in substantia nigra were seen in two individuals. The Asp517Metfs*19 and Ser126Metfs*8 fibroblasts were structurally and functionally indistinguishable. The most prominent ultrastructural changes of the mutant fibroblasts were reduced presence of free ribosomes, the appearance of elongated endoplasmic reticulum and strikingly increased number of mitochondria and small vesicles. When chronically treated with choline, those characteristics disappeared and mutant ultrastructure resembled healthy control cells. Functional analysis revealed diminished choline transport yet the membrane phosphatidylcholine content remained unchanged. As part of the mechanism to preserve choline and phosphatidylcholine, choline transporter deficiency was implicated in impaired membrane homeostasis of other phospholipids. Choline treatments could restore the membrane lipids, repair cellular organelles and protect mutant cells from acute iron overload. In conclusion, we describe a novel childhood-onset neurometabolic disease caused by choline transporter deficiency with autosomal recessive inheritance.

[Good social function in a child with severe visual loss due to colobomas]. / God social funktion hos et barn med kraftig synsnedsættelse på grund af korioretinale kolobomer

A child born with bilateral colobomas was referred to the department of ophthalmology. At birth the child was assumed to be blind. During the follow-up period of seven years his visual acuity improved to 0.08 and he became a socially and intellectually well-functioning child. He attended a normal school, and in his spare time he was able to ride his bike, swim and play football. This example illustrates how difficult it is to predict the visual and social function of a newborn with poor vision.

[Traumatic optic neuropathy after fall with a bamboo stick]. / Udvikling af opticusneuropati efter beskedent øjetraume.

Traumatic optic neuropathy (TON) is a rare and potentially vision-threatening condition caused by ocular or head trauma. The treatment of TON is controversial with no evidence-based guidelines. We describe a case of an eight-year-old boy, who lost his vision on the right eye after having had a trauma of his left lower eyelid when he fell with a bamboo stick. Vision loss was not detected until ten days after the accident, where there were no light perception and a relative afferent pupillary defect. We attributed the vision loss to TON and no treatment was given. Within months optic disc pallor developed.

Association of CHRDL1 mutations and variants with X-linked megalocornea, Neuhäuser syndrome and central corneal thickness.

We describe novel CHRDL1 mutations in ten families with X-linked megalocornea (MGC1). Our mutation-positive cohort enabled us to establish ultrasonography as a reliable clinical diagnostic tool to distinguish between MGC1 and primary congenital glaucoma (PCG). Megalocornea is also a feature of Neuhäuser or megalocornea-mental retardation (MMR) syndrome, a rare condition of unknown etiology. In a male patient diagnosed with MMR, we performed targeted and whole exome sequencing (WES) and identified a novel missense mutation in CHRDL1 that accounts for his MGC1 phenotype but not his non-ocular features. This finding suggests that MMR syndrome, in some cases, may be di- or multigenic. MGC1 patients have reduced central corneal thickness (CCT); however no X-linked loci have been associated with CCT, possibly because the majority of genome-wide association studies (GWAS) overlook the X-chromosome. We therefore explored whether variants on the X-chromosome are associated with CCT. We found rs149956316, in intron 6 of CHRDL1, to be the most significantly associated single nucleotide polymorphism (SNP) (p = 6.81×10(-6)) on the X-chromosome. However, this association was not replicated in a smaller subset of whole genome sequenced samples. This study highlights the importance of including X-chromosome SNP data in GWAS to identify potential loci associated with quantitative traits or disease risk.

Mortality in patients with central retinal vein occlusion.

PURPOSE: To assess mortality in patients with central retinal vein occlusion (CRVO). DESIGN: Registry-based cohort study. PARTICIPANTS AND CONTROLS: Four hundred thirty-nine photographically verified CRVO patients and a control cohort of 2195 unexposed subjects matched by age and gender and alive on the date CRVO was diagnosed in the corresponding case. METHODS: Data from nationwide registries were used to compare mortality rates in CRVO patients with a control cohort over a mean follow-up of 5.1 years for cases and of 5.7 years for controls. MAIN OUTCOME MEASURES: Hazard ratios (HRs) obtained by Cox regression and standardized mortality ratios (SMRs) stratified by age and gender served as measures of relative mortality risk. RESULTS: Mortality was higher in patients with CRVO (HR, 1.45; 95% confidence interval [CI], 1.19-1.76) than in the control cohort, adjusted for age, gender, and time of diagnosis. Mortality was comparable between the 2 groups (HR, 1.19; 95% CI, 0.96-1.46) when adjusting for overall occurrence of cardiovascular disease and diabetes. Subgroup analysis found that the age-stratified mortality rate was increased significantly in the total group of men (SMR, 1.27; 95% CI, 1.03-1.56) and in women 60 to 69 years of age (SMR, 1.94; 95% CI, 1.22-3.08). CONCLUSIONS: Central retinal vein occlusion was associated with an overall increase in mortality compared with controls that was attributed statistically to cardiovascular disorders and diabetes. We recommend treatment of hypertension and diabetes, if present, and referral of patients found to have CRVO who are not already being treated by a primary care physician.

Xeroderma Pigmentosum-Trichothiodystrophy overlap patient with novel XPD/ERCC2 mutation.

Xeroderma Pigmentosum (XP), Trichothiodystrophy (TTD) and Cockayne Syndrome (CS) are rare, recessive disorders caused by mutational defects in the Nucleotide Excision Repair (NER) pathway and/or disruption of basic cellular DNA transcription. To date, a multitude of mutations in the XPD/ERCC2 gene have been described, many of which give rise to NER- and DNA transcription related diseases, which share certain diagnostic features and few overlap patients have been described. Despite increasing understanding of the roles of XPD/ERCC2 in mammalian cells, there is still weak predictability of somatic outcome from many of these mutations. We demonstrate a patient, believed to represent an overlap between XP and TTD/CS. In addition to other organ dysfunctions, the young man presented with Photosensitivity, Ichthyosis, Brittle hair, Impaired physical and mental development, Decreased fertility and Short stature (PIBIDS) suggestive of TTD, but lacking the almost patognomonic "tiger tail" banding of the hair under polarized light. Additionally, he developed basal cell carcinoma aged 28, as well as adult onset kidney failure, features normally not associated with TTD but rather XP/CS. His freckled appearance also suggested XP, but fibroblast cultures only demonstrated x2 UV-sensitivity with expected NER and TFIIH-activity decrease. Genetic sequencing of the XPD/ERCC2 gene established the patient as heterozygote compound with a novel, N-terminal Y18H mutation and a known C-terminal (TTD) mutation, A725P. The possible interplay between gene products and the patient phenotype is discussed.

Comorbidity in patients with branch retinal vein occlusion: case-control study.

OBJECTIVES: To evaluate comorbidity before and after the diagnosis of branch retinal vein occlusion to determine whether it is a consequence of arterial thickening and therefore could serve as a diagnostic marker for other comorbidities and to evaluate the risk factors for the development of such occlusion. DESIGN: Case-control study with prospective follow-up data from Danish national registries. SETTING: Four secondary referral centres covering about 80% of the Danish population (4.4 million). PARTICIPANTS: 1168 patients with photographically verified branch retinal vein occlusion and 116,800 controls alive and aged ≥ 40 when the occlusion was diagnosed in the corresponding case. MAIN OUTCOME MEASURES: The risk of comorbidity 10 years and 1 year before the diagnosis of branch retinal vein occlusion and the incident comorbidity in a mean period of seven years after the diagnosis, with odds ratios and incidence rate ratios adjusted for age, sex, and year of diagnosis. RESULTS: Risk factors present 10 years and 1 year before the diagnosis of branch retinal vein occlusion included peripheral artery disease (odds ratio 1.83, 95% confidence interval 1.14 to 2.95), diabetes (1.74, 1.40 to 2.17) and arterial hypertension (2.16, 1.86 to 2.51). After the diagnosis, patients had an increased risk of developing arterial hypertension (incidence rate ratio 1.37, 95% confidence interval 1.15 to 1.57), diabetes (1.51, 1.17 to 2.04), congestive heart failure (1.41, 1.12 to 1.68), and cerebrovascular disease (1.49, 1.27 to 1.76). CONCLUSION: Diabetes, hypertension, and peripheral artery disease are associated with an increased risk of developing branch retinal vein occlusion up to a decade later. Branch retinal vein occlusion was associated with an increased risk of subsequently developing hypertension, diabetes, congestive heart failure, and cerebrovascular disease, emphasising the importance of preventive initiatives. These results fit the assumption that branch retinal vein occlusion is a consequence of arterial thickening and that the arteriovenous crossing signs that precede it are hallmarks of arterial disease.

[Two cases of Richner-Hanhart syndrome (oculocutaneous tyrosinemia)]. / To tilfaelde af Richner-Hanharts syndrom (okulokutan tyrosinaemi).

Richner-Hanhart syndrome or oculocutaneous tyrosinemia is characterized by painful palmo-plantar keratoderma, keratitis with photophobia and progressive mental impairment. The syndrome is caused by deficient hepatic tyrosine aminotransferase and is inherited as an autosomal recessive trait. We report a 28 year-old woman with lifelong photophobia, eye pain and painful plantar hyperkeratotic lesions, necessitating use of a wheelchair. A few days after instituting tyrosine lowering therapy, her eye symptoms disappeared and she could walk without pain. Her brother was later diagnosed with the same disease.

Mortality in patients with branch retinal vein occlusion.

PURPOSE: To assess the impact of branch retinal vein occlusion (BRVO), a condition related to arteriolar wall thickening, as a prognostic marker of mortality. DESIGN: Long-term follow-up study comparing cases with background population. PARTICIPANTS: Patients diagnosed with BRVO. METHODS: Diagnosis of BRVO confirmed by fundus photographic records including color diapositives and fluorescein angiograms. MAIN OUTCOME MEASURES: Observed and expected numbers of deaths determined from comprehensive civic records in cases compared with the background population (5.4 million). RESULTS: Branch retinal vein occlusion was found in 329 patients (173 women, 156 men) born between 1902 and 1956, who were 39 to 91 years old when diagnosed between 1973 and 1998. Follow-up was concluded on July 8, 2004, when 144 deaths were recorded in patients (74 women, 70 men), compared with an expected number of 145.5 deaths in the background population (standardized mortality rate, 0.99; 95% confidence interval, 0.84-1.16). Stratified analyses revealed no significant effect of age, gender, or time of diagnosis. CONCLUSIONS: In this study of 329 patients with BRVO, we found no significant difference in mortality between patients and the background population. An association between BRVO and cardiovascular/cerebrovascular risk factors has previously been documented in cross-sectional studies. The contrasting outcome in this longitudinal study may have been influenced by interventions instituted after the diagnosis of BRVO was made and by preferential survival before the diagnosis of BRVO of the more fit patients with the necessary precursor condition of having arteriovenous nicking, which is more prevalent in subjects with diabetes and hypertension.