Two cases of Wolfram syndrome

Wolfram syndrome is a rare autosomal recessive neurodegenerative disease; it is characterized by the appearance of diabetes mellitus in childhood associated with bilateral optic atrophy that often leads to blindness. Insipid diabetes, deafness, psychiatric disorders, anosmia, anomalies of the urinary tract, nystagmus, ataxia, and myoclonias are less frequent. We report two cases of Wolfram syndrome, diagnosed in a 12-year-old girl and a 13-year-old boy. In each case, there was a history of diabetes mellitus; they consulted for a progressive loss of vision. Ophthalmologic examination objectified that visual acuity was reduced to finger counting in both eyes as well as isolated bilateral optic atrophy and constriction of the peripheral visual field. Through these two cases and a review of the literature, we propose to study the genetic and clinical aspects of Wolfram syndrome.     

Wolfram syndrome. Three case reports

Wolfram syndrome is a rare disorder defined by the occurrence of diabete mellitus, diabete insipidus, optic atrophy and deafness; DIDMOAD is a commonly accepted acronym. We report 3 further cases: two girls and one boy. Their age ranged from 12 to 17 years. The diagnosis was based on the presence of juvenile diabete mellitus, bilateral optic atrophy, urologic signs, with urinary tract dilation; and deafness in two cases. The ophthalmic signs of Wolfram syndrome are progressive decrease in visual acuity, constriction of the peripheral visual field with or without central scotoma, color vision disturbances and bilateral optic disc atrophy. Diabetic retinopathy is a rare complication. The other clinical features are discussed so as to differentiate between Wolfram syndrome and other optic atrophies associated with diabete mellitus. We discuss of the pathogenic hypothesis including the mitochondrial dysfunction.     

Evidence of retinal degeneration in Wolfram syndrome

Purpose: Wolfram syndrome is characterized by early onset diabetes mellitus, diabetes insipidus, deafness, and optic atrophy, but retinal degeneration has not been described as a major component of the phenotype. We present two cases with Wolfram syndrome and evidence of retinal degeneration.

Materials and Methods: Observational case series. Patients underwent complete ocular examinations as well as retinal imaging and electroretinography.

Results: Both patients had electroretinographic evidence of retinal dysfunction/degeneration in addition to optic atrophy with an otherwise normal-appearing retina.

Conclusions: Some patients with Wolfram syndrome have a mild retinal degeneration that may be a manifestation of the neuronal involvement that is present in this condition.     

Ophthalmologic findings in fifteen patients with Wolfram syndrome

PURPOSE: To look for ophthalmologic abnormalities in 15 patients with Wolfram syndrome, also known as DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and deafness). METHODS: Fifteen patients from four inbred families diagnosed as having Wolfram syndrome at the National Center for Diabetes, Endocrinology and Genetics, in Amman, Jordan, were evaluated ophthalmologically. Their examination included best-corrected visual acuity, color vision testing, pupillary light reflexes, slit-lamp biomicroscopy and fundus examination. Fundus fluorescein angiography was done in all patients. RESULTS: The prevalence of optic atrophy was (93.3%), colordefect (92.9%), cataract (66.6%), pigmentary retinopathy (30%) and diabetic retinopathy (20%). Abnormal pupillary light reflexes and nystagmus were also reported. CONCLUSIONS: Although ourgroup of patients was genetically heterogeneous, the ophthalmic findings are consistent with those reported in other series, except for cataract which was highly prevalent but mild and did not contribute significantly to loss of vision.     

Pigmentary maculopathy in a patient with Wolfram syndrome

CASE REPORT: We describe a rare association of pigmentary maculopathy with Wolfram syndrome not previously reported in the literature. A 12-year-old boy presented to the retina service with a diagnosis of Wolfram syndrome and a history of poor central vision. The patient was found to have bilateral atrophic pigmentary maculopathy that was confirmed with fluorescein angiography. COMMENTS: Wolfram syndrome may present with a pigmentary maculopathy and this rare finding may assist the clinician in making appropriate genetic referral when this diagnosis is suspected.     

Wolfram syndrome: A clinical study of two cases

Two unrelated patients with two different images of Wolfram (or DIDMOAD) syndrome are presented: a 19—year old woman suffering from all the important features of this syndrome, and a 38—year old man showing two major characteristics but several minor abnormalities. This syndrome should be considered in young diabetic patients with unexplained visual loss or with polyuria and polydipsia in the presence of adequate blood sugar control. An early diagnosis is important to prevent unnecessary diagnostic investigations.     

Wolfram综合征一家系的临床及遗传学分析

目的:研究由WFS1基因突变所导致的常染色体隐性遗传Wolfram综合征的临床特征和遗传学背景。方法:应用临床检查,基因分析和生物信息学方法研究一常染色体隐性遗传Wolfram综合征家系。结果:发现先证者及哥哥患糖尿病、色弱及视神经病变,此外其兄患尿崩症。全外显子组分析显示在兄弟二人的WFS1基因8号外显子存在两种杂合变异,即c.941G>A(p.W314X)和c.2309T>G(p.F770C),并在该家系中与临床表型共分离。结论:WFS1基因的复合杂合突变与该家系Wolfram综合征相关,其中c.941G>A(p.W314X)尚未见报道。     

Wolfram syndrome: clinical and genetic analysis in two sisters

Wolfram syndrome is a severe genetic disorder defined by the association of diabetes mellitus, optic atrophy, deafness, and diabetes insipidus. Two sisters complained of progressive visual loss. Fundus examination evidenced optic atrophy. Their past medical history revealed diabetes mellitus and deafness since childhood. The association of these symptoms made the diagnosis of Wolfram syndrome possible. It was confirmed by molecular analysis, which evidenced composite WFS1 heterozygous mutations inherited from both their mother and father. Ophthalmologists should be aware of the possibility of Wolfram syndrome when diagnosing optic atrophy in diabetic children.     

Incomplete Wolfram syndrome: Clinical and electrophysiologic study of two familial cases

Wolfram, or DIDMOAD, syndrome is a genetic disorder characterized by diabetes insipidus, diabetes mellitus, optic atrophy and deafness. We studied a family in which only diabetes mellitus and primary optic atrophy were present in three female siblings. Two of these patients, fraternal twins, were subjected to a complete electrophysiologic examination. The possibility of an incomplete clinical expression of Wolfram syndrome, hypotheses of its genetic transmission, and diagnostic problems are discussed.     

A long-term follow-up of a patient with DIDMOAD (Wolfram) syndrome

A 19-year-old Japanese woman developed diabetes mellitus, diabetes insipidus and optic atrophy. Other abnormal ocular findings included color blindness, elevated dark adaptation threshold and constriction of visual fields. Diabetic retinopathy, which is considered to be rare in this syndrome, also was found in the fundi of this patient. During the nine-year follow-up period, diabetic retinopathy deteriorated despite treatment by photocoagulation and vitrectomy, suggesting the importance of ophthalmological examinations in patients with DIDMOAD syndrome.     

Clinical variability in hereditary optic neuropathies: Two novel mutations in two patients with dominant optic atrophy and Wolfram syndrome

Dominant optic atrophy (DOA) and Wolfram syndrome share a great deal of clinical variability, including an association with hearing loss and the presence of optic atrophy at similar ages. The objective of this paper was to discuss the phenotypic variability of these syndromes with respect to the presentation of two clinical cases.We present two patients, each with either DOA or Wolfram syndrome, and contribute to the research literature through our findings of two novel mutations.The overlapping of several clinical characteristics in hereditary optic neuropathies can complicate the differential diagnosis. Future studies are needed to better determine the genotype-phenotype correlation for these diseases.     

Wolfram syndrome 1 (WFS1) protein expression in retinal ganglion cells and optic nerve glia of the cynomolgus monkey

Wolfram syndrome (WFS1, OMIM 222300) is a rare genetic disorder associated with multiple organ abnormalities, most prominently optic nerve atrophy and diabetes. Mutations in the WFS1 gene coding for wolframin have been identified. The pathogenesis for optic nerve atrophy remains elusive. We here tested the hypothesis that wolframin is expressed in glial cells of the optic nerve and in retinal ganglion cells in the cynomolgus monkey. Paraffin sections through the retina and optic nerve were examined with immunohistochemistry using affinity-purified antibodies to wolframin. Retinal ganglion cells and optic nerve glial cells were found to be strongly labeled. Dual dysfunction of wolframin in optic nerve glial cells and retinal ganglion cells may explain the progressive optic nerve atrophy in Wolfram syndrome.     

Wolfram Syndrome: a rare optic neuropathy in youth with type 1 diabetes

Wolfram Syndrome (WS) is a rare, autosomal recessive disorder that causes non-autoimmune type 1 diabetes. The etiology involves a single gene mutation of the wolframin protein inducing endoplasmic reticulum stress and apoptosis in selected cell types with resultant diabetes insipidus, diabetes mellitus, optic atrophy, and sensory-neural deafness. Symptoms are initially absent and signs within the posterior segment of the eye are usually the earliest indicator of WS.These cases characterize unusual and poorly described findings of pigmentary maculopathy in WS and illustrate the importance of collaboration between diabetes and eye care providers; especially in cases of non-autoimmune type 1 diabetes exhibiting atypical human leukocyte-associated antigen haplotypes.     

假性剥脱综合征中的Charles Bonnet综合征(英文)

目的:报道1例进展期假性剥脱性青光眼中的Charles Bonnet综合征。方法:病例报告。结果:一例92岁的马来男性诉2a前出现幻视,并加重2mo。称看见成人及百余儿童生动活泼地出现在不同场合。他甚至有几次看见一只兔子偶尔跑过他的房间。但是,他觉察到这是一种异常的经历。与同年龄人相比,他的认知功能是正常的。精神病学评估包括精神状态检查是正常的。他曾经被诊断患有开角型青光眼,左眼以前接受过常规的白内障手术和小梁切除术。其视力为右眼手动,左眼6/7.5(0.8)伴管状视野。眼底镜检查显示左眼进行性青光眼性视杯加深。目前诊断为右眼大泡性角膜病变合并绝对期青光眼,左眼进展期假性剥脱性青光眼,有功能性滤过泡。结论:对诉有幻视的老年患者,特别是在痴呆和精神病的诊断标准不明确的情况下,诊断通常是很困难的。如果这些患者洞察到不复存在的东西进入其视觉范围,并伴有视觉功能恶化,应高度怀疑患有Charles Bonnet综合征的可能。