Bilateral Optic Nerve Atrophy Research Articles

Expanding phenotype of MED13-associated syndrome presenting novel de novo missense variant in a patient with multiple congenital anomalies

BackgroundWhole exome sequencing allows rapid identification of causative single nucleotide variants and short insertions/deletions in children with congenital anomalies and/or intellectual disability, which aids in accurate diagnosis, prognosis, appropriate therapeutic interventions, and family counselling. Recently, de novo variants in the MED13 gene were described in patients with an intellectual developmental disorder that included global developmental delay, mild congenital heart anomalies, and hearing and vision problems in some patients.ResultsHere we describe an infant who carried a de novo p.Pro835Ser missense variant in the MED13 gene, according to whole exome trio sequencing. He presented with congenital heart anomalies, dysmorphic features, hydrocephalic changes, hypoplastic corpus callosum, bilateral optic nerve atrophy, optic chiasm atrophy, brain stem atrophy, and overall a more severe condition compared to previously described patients.ConclusionsTherefore, we propose to expand the MED13-associated phenotype to include severe complications that could end up with multiple organ failure and neonatal death.

MRI Findings in Leber’s Hereditary Optic Neuropathy: A case report

Background: Leber’s hereditary optic neuropathy (LHON) is a rare genetic condition which is mainly presented with painless, sub-acute central unilateral vision loss followed by contralateral vision loss after few weeks to months. Young adults are typically affected with men preponderance. Relatively, it is a common cause of blindness as a result of mutation in mitochondrial DNA (mtDNA). Case report: We reported the case of two brothers, who had recent history of vision loss. Fundoscopy examination revealed bilateral optic nerve atrophy along with vessel narrowing and absent macular reflex. We performed MRI bilateral orbits with contrast which revealed abnormal signals and atrophy of the optic nerves suggesting optic neuritis. Conclusion: Whenever young males develop bilateral sequential vision loss with a positive family history, the diagnosis of Leber’s hereditary optic neuropathy should be suspected. Ophthalmological examination may reveal signs suggestive of Leber’s hereditary optic neuropathy. MRI may demonstrate edema signals in both optic nerve along with thinning of nerve fibers suggesting nerve atrophy. MRI is considered an useful tool to show optic nerve abnormality and optic neuritis.

OUR EXPERIENCE IN THE TREATMENT OF CHOROIDAL OSTEOMA

Choroidal osteoma is a rare, benign formation of the choroid, which occurs most often in women of working age and characterized by the formation of neovascularization in 31-47% of cases, even the development of bilateral optic nerve atrophy is described. The etiology of the disease remains unknown, persistent associations with other ocular or systemic diseases, as well as with any disorders of calcium or phosphorus metabolism, have not been described in the literature. The paper presents a clinical case of diagnosis and treatment of choroidal osteoma, which was combined with secondary serous retinal detachment. A patient underwent a closed subtotal vitrectomy with endotamponade with 1300cc silicone oil due to an existing choroidal osteoma, which was complicated by secondary retinal detachment. The course of the early postoperative period was uneventful, but 2 weeks after surgical treatment, signs of inflammation of the anterior part of the vascular tract occurred with the formation of precipitates and secondary ophthalmohypertension, decrease in visual acuity, the Tyndall effect, which gradually led to the formation of a pigmented exudate in the anterior chamber. Anti-inflammatory and hypotensive therapy allowed to minimize the manifestation of inflammatory changes and to restore normotonia. As a result of the complex treatment, it was possible to improve the visual acuity and restore the morphological structure of the retina, but the functional results after the treatment remained low, which, in our opinion, may be related to the topographical location of the osteoma, since localization in the paramacular zone can not have some positive prognosis in postoperative period. Also, the existing long-term retinal detachment and complications in the early postoperative period could affect the low functional results after the surgical treatment.

NKX6-2 Disease in Two Unrelated Patients with Early-Onset Spastic Quadriplegia and Diffuse Hypomyelinating Leukodystrophy

Recently, biallelic variants in NKX6-2 have been reported to cause central nervous system hypomyelination. Clinical presentation of previously reported patients included two distinct phenotypes: a neonatal-onset with severe presentation, and a milder childhood-onset form. To date, there have been 40 individuals in 24 unrelated families from different ethnic backgrounds, due to 16 distinct variants identified by whole exome sequencing. We report two individuals from two unrelated families who presented with hypomyelination, spastic quadriplegia, nystagmus, and global developmental delay. Using clinical whole exome sequencing, we identified a newly reported, pathogenic, nonsense variant in case 1 (c.475C>T (p.Gln159Ter)), and a novel frameshift variant (c.234delG (p.Leu79CysfsX109)) in case 2. The clinical phenotype and the neuroimaging were similar in both patients and consistent with the neonatal onset form. The phenotypic overlap with other CNS hypomyelinating disorders, the intrafamilial and interfamilial variability and the non-diagnostic initial genetic and metabolic work up add significant diagnostic challenge. We thus, recommend comprehensive molecular testing by whole exome/genome sequencing as the initial test for patients presentingwith early onset nystagmus, hypotonia, rapidly progressive spastic quadriplegia, bilateral optic nerve atrophy, and diffuse hypomyelination.

Magnetic resonance imaging negative myelopathy in Leber’s hereditary optic neuropathy: a case report

BackgroundLeber’s hereditary optic neuropathy (LHON) is a common form of mitochondrial disease. The typical clinical presentation of LHON is subacute, painless loss of vision resulting from bilateral optic nerve atrophy. Moreover, extra-ocular manifestations such as cardiac conduction abnormalities and neurological manifestations such as multiple sclerosis (MS) like disease or parkinsonism are encountered in some patients. Abnormal findings in spinal cord MR imaging or in the cerebrospinal fluid (CSF) have been observed in previous cases of LHON-associated myelopathy.Case presentationWe report a male patient with LHON who developed symptoms of myelopathy including gait unsteadiness, enhanced deep tendon reflexes and sensory loss of the lower extremities. Imaging of the brain and spinal cord, CSF analysis, as well as neurography and electromyography did not disclose any abnormalities. The somatosensory evoked potential (SEP) findings were suggestive of dorsal column dysfunction.ConclusionsThe patient case demonstrates that myelopathy associated with LHON can present without abnormal findings in central nervous system MR imaging or in the CSF, and without evidence suggestive of multiple sclerosis or MS-like disease. The dorsal column seems to be particularly vulnerable to myelopathy changes in LHON. Evoked potential investigations may assist in confirming the diagnosis, when clinical features are in line with myelopathy but findings in CSF analysis and central nervous system imaging are normal.

A case of cutis verticis gyrata‐mental retardation syndrome accompanied by various neurological abnormalities

AbstractWe report a 44‐year‐old male with cutis verticis gyrate (CVG)‐mental retardation syndrome. His backhead skin formed several folds, which were diagnosed as CVG. Neurological examinations revealed bilateral marked visual acuity loss, deaf‐mutism, mild mental retardation, bilateral Babinski's sign, severe spastic paraplegia, and cerebellar ataxia. Brain magnetic resonance imaging showed atrophy of the cerebellum and the corpus callosum. The fundus showed bilateral optic nerve atrophy. The clinical features had the primary non‐essential form in the CVG classification. Our patient was important because of the low frequency of this form in mental retardation.

The Novel KIF1A Missense Variant (R169T) Strongly Reduces Microtubule Stimulated ATPase Activity and Is Associated With NESCAV Syndrome.

KIF1A is a microtubule-dependent motor protein responsible for fast anterograde transport of synaptic vesicle precursors in neurons. Pathogenic variants in KIF1A have been associated with a wide spectrum of neurological disorders. Here, we report a patient presenting a severe neurodevelopmental disorder carrying a novel de novo missense variant p.Arg169Thr (R169T) in the KIF1A motor domain. The clinical features present in our patient match with those reported for NESCAV syndrome including severe developmental delay, spastic paraparesis, motor sensory neuropathy, bilateral optic nerve atrophy, progressive cerebellar atrophy, epilepsy, ataxia, and hypotonia. Here, we demonstrate that the microtubule-stimulated ATPase activity of the KIF1A is strongly reduced in the motor domain of the R169T variant. Supporting this, in silico structural modeling suggests that this variant impairs the interaction of the KIF1A motor domain with microtubules. The characterization of the molecular effect of the R169T variant on the KIF1A protein together with the presence of the typical clinical features indicates its causal pathogenic effect.

Neurofilament light chain as biomarker in idiopathic intracranial hypertension.

Damage of the optic nerve is the major complication of idiopathic intracranial hypertension. A biomarker indicative for optic nerve damage would help identifying high-risk patients requiring surgical procedures. Here, we studied the potential of cerebrospinal fluid neurofilament to predict idiopathic intracranial hypertension-induced optic nerve damage. In two centers, serum and cerebrospinal fluid of 61 patients with clinically suspected idiopathic intracranial hypertension were prospectively collected. Neurofilament concentrations were measured and related to ophthalmological assessment. The average cerebrospinal fluid neurofilament concentration in patients with moderate and severe papilledema was increased compared to patients with minor and no papilledema (1755 ± 3507 pg/ml vs. 244 ± 102 pg/ml; p < 0.001). Cerebrospinal fluid neurofilament concentrations correlated with the maximal lumbar puncture opening pressure (r = 0.67, p < 0.001). In patients fulfilling the Friedman criteria for idiopathic intracranial hypertension with or without papilledema (n = 35), development of bilateral visual field defects and bilateral atrophy of the optic nerve were associated with increased average age-adjusted cerebrospinal fluid neurofilament concentrations. At last follow-up (n = 30), 8/13 of patients with increased, but only 3/17 with normal, cerebrospinal fluid neurofilament had developed bilateral visual field defects and/or bilateral optic nerve atrophy resulting in a sensitivity of 72.7% and a specificity of 73.7% of cerebrospinal fluid neurofilament to detect permanent optic nerve damage. Cerebrospinal fluid neurofilament is a putative biomarker for optical nerve damage in idiopathic intracranial hypertension.

Optic Nerve Atrophy in Heroin Intoxication

Drug dependence is one of important social problems in modern society. It became more actual because of the high morbidity in young working-age patients. The central nervous system is the main target for psychoactive substances. Long-term drug intoxication results in functional and structural brain alterations, it leads to cognitive impairment and disturbances of higher mental functions rendering patients’ disadapted in their work and daily life activities. Eye disorders due to drug abuse are multifaceted and can vary from conjunctival damage to severe endogenous endophthalmitis. Opioid dependence can result not only from intentional self-administration of narcotic drugs, but also from long-term prescribed use of these medicinal products owing to their potent analgesic effect exhibited in somatically ill patients with severe chronic pain. Opioid derivatives act as partial or full agonists of three types of opioid receptors (δ, κ, and µ) extensively expressed by the neurons of the central and, to a lesser extent, peripheral nervous system. The most dangerous complication of intoxication with this group narcotic drugs is opioid induced-respiratory depression resulting in hypoxaemia and hypercapnia. The paper presents a case report of bilateral optic nerve atrophy that developed in a young female patient after a long period of intravenous heroin use. There are practically no reports of optic nerve damage due to heroin intoxication in the current literature. Possible optic nerve atrophy mechanisms under discussion include generalized hypoxia developing against a background of chronic heroin intoxication and direct toxicity of admixtures used to dilute home-made narcotic drugs. In view of the growing use of these substances, physicians have to consider their effects in the differential diagnosis in patients with atypical eye disorders.

Ocular Phenotype and Complications in Patients with Tuberous Sclerosis Complex (TSC)

Evaluation and comparison of the ocular phenotype in patients diagnosed with tuberous sclerosis complex (TSC). Analysis of ocular complications during follow-up. A retrospective chart review was performed of patients with TSC who had received an ocular examination at the eye clinic of the University Hospital Zurich. Data were analysed on visual acuity (VA) assessment, refraction, anterior and posterior eye examination including the distinction of different types of hamartomas and, when available, visual fields. The study was approved by the Cantonal Ethics Committee of Zurich. A total of 30 patients who were diagnosed with TSC (19 female, 11 male) were included in the analysis. The age at first examination varied from 7 months to 44 years (mean 13.3 years, standard deviation 11.31). 17/30 patients received a follow-up examination between 4 months and 19 years (mean 4.3 years, standard deviation 5.24). Data of VA were available in 26/30 patients, of whom 22 had normal vision in both eyes. The causes of reduced VA in the 4 patients were: complications of a subependymal giant cell astrocytoma followed by a bilateral optic nerve atrophy; vigabatrin-associated optic atrophy; anterior segment dysgenesis; unilateral amblyopia. Adequate VA testing was not possible in 4 patients because of intellectual disabilities. Retinal hamartomas were described in 15/30 patients: 8 unilateral, 7 bilateral. The flat hamartoma type was described in 10/15 patients, the multinodular type in 6/15 patients. The ocular phenotype in our patient cohort shows similar TSC involvement to that described in the literature. Patients diagnosed with TSC require regular ophthalmic examinations to diagnose secondary ocular complications, such as papilloedema, severe vision loss or visual field constriction.

A novel homozygous AP4B1 mutation in two brothers with AP‐4 deficiency syndrome and ocular anomalies

Adaptor protein complex-4 (AP-4) is a heterotetrameric protein complex which plays a key role in vesicle trafficking in neurons. Mutations in genes affecting different subunits of AP-4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been recently associated with an autosomal recessive phenotype, consisting of spastic tetraplegia, and intellectual disability (ID). The overlapping clinical picture among individuals carrying mutations in any of these genes has prompted the terms "AP-4 deficiency syndrome" for this clinically recognizable phenotype. Using whole-exome sequencing, we identified a novel homozygous mutation (c.991C>T, p.Q331*, NM_006594.4) in AP4B1 in two siblings from a consanguineous Pakistani couple, who presented with severe ID, progressive spastic tetraplegia, epilepsy, and microcephaly. Sanger sequencing confirmed the mutation was homozygous in the siblings and heterozygous in the parents. Similar to previously reported individuals with AP4B1 mutations, brain MRI revealed ventriculomegaly and white matter loss. Interestingly, in addition to the typical facial gestalt reported in other AP-4 deficiency cases, the older brother presented with congenital left Horner syndrome, bilateral optic nerve atrophy and cataract, which have not been previously reported in this condition. In summary, we report a novel AP4B1 homozygous mutation in two siblings and review the phenotype of AP-4 deficiency, speculating on a possible role of AP-4 complex in eye development.

Juvenile nephronophthisis and dysthyroidism: a rare association.

Nephronophthisis, an autosomal recessive kidney disease, represents the most frequent genetic cause of end-stage kidney disease in the first three decades of life. A 27-year-old male was presented with gait imbalance, sever pruritus since 10days prior time of admission. In past medical history, he had bilateral cataract, torsional nystagmus, and bilateral optic nerve atrophy since 2years of age. He was also mentioned history of multinodular goiter with dysfunctional thyroid state since 2years before admission. At admission bilateral blindness, torsional nystagmus, asymmetric thyromegaly with nodularity was found in physical examination. Laboratory tests showed elevated urea and creatinine (200, 10.7mg/dl), hypomagnesemia (1.1mEq/l), decreased thyroid stimulating hormone (<0.004mIU/l). Ophthalmologist consultation confirmed retinitis pigmentosa. Renal sonography showed small-sized kidneys. Brain magnetic resonance imaging did not reveal molar tooth sign. Genetic testing performed and a large homozygous deletion at the NPHP1 gene locus was found. The patient was diagnosed with juvenile nephronophthisis and consideration of dysthyroidism as extrarenal manifestation of nephronophthisis is suggested in this case. Furthermore, loss of function mutation in SLC41A1 gene that leads to magnesium depletion must be noted in patients with suspected to nephronophthisis.

Bilateral Posterior Ischaemic Optic Neuropathy Secondary to Diabetic Ketoacidosis: An Unfortunate Cure for Diabetic Retinopathy

Purpose: To report a case of bilateral posterior ischaemic optic neuropathy secondary to diabetic ketoacidosis. Methods: Case history with multimodal imaging, including colour fundus photography, fundus fluorescein angiography, optical coherence tomography, and magnetic resonance imaging with high resolution diffusion weighted imaging. Results: We report a 29-year-old female with bilateral posterior ischaemic optic neuropathy following diabetic ketoacidosis resulting in no perception of light vision in both eyes, confirmed on magnetic resonance imaging with high resolution diffusion weighted imaging. We also document the resolution of proliferative diabetic retinopathy following the onset of bilateral optic nerve atrophy. Conclusion: Bilateral posterior ischaemic optic neuropathy can occur following diabetic ketoacidosis, and proliferative diabetic retinopathy can resolve following the onset of optic nerve atrophy. If posterior ischaemic optic neuropathy is suspected, magnetic resonance imaging with high resolution diffusion weighted imaging may aid in confirming the diagnosis.

Bilateral Compressive Optic Neuropathy Secondary to Tuberculum Sella Meningioma in Pregnancy

A 37-year-old primigravida in her second trimester presented with bilateral painless progressive visual loss. Her vision was hand motion in both eyes. Both pupils were dilated with sluggish reaction to light. Both fundus appeared myopic with bilateral optic atrophy. Magnetic resonance imaging (MRI) of the brain revealed a suprasellar mass with optic chiasm compression and bilateral optic nerve atrophy. As the mass has compromised her vision, a semi-emergency craniotomy and excision of tumour was performed. Histopathological examination confirmed the diagnosis of low grade meningothelial meningioma. Both mother and foetus were well after the surgery. However, post-operatively her vision remained poor due to optic nerve atrophy.

Tardily accelerated neurologic deterioration in two-step thallium intoxication

Thallium intoxication was reported in cases with accidental ingestion, suicide attempt, and criminal adulteration. Reported cases were mostly one-time ingestion, therefore, the clinical course of divisional ingestion has not been fully known. Here, we report a case with two-step thallium intoxication manifesting as tardily accelerated neurologic deterioration. A 16-year-old adolescent was cryptically poisoned with thallium sulfate twice at an interval of 52days. After the first ingestion, neurologic symptoms including visual loss, myalgia, and weakness in legs developed about 40days after the development of acute gastrointestinal symptoms and alopecia. After the second ingestion, neurologic symptoms deteriorated rapidly and severely without gastrointestinal or cutaneous symptoms. Brain magnetic resonance imaging exhibited bilateral optic nerve atrophy. Nerve conduction studies revealed severe peripheral neuropathies in legs. Thallium intoxication was confirmed by an increase in urine thallium egestion. Most of the neurologic manifestations ameliorated in two years, but the visual loss persisted. The source of thallium ingestion was unraveled afterward because a murder suspect in another homicidal assault confessed the forepast adulteration. This discriminating clinical course may be attributable to the cumulative neurotoxicity due to the longer washout-time of thallium in the nervous system than other organs. It is noteworthy that the divisional thallium intoxication may manifest as progressive optic and peripheral neuropathy without gastrointestinal or cutaneous symptoms.

Spectrum of MRI findings in 58 patients with methanol intoxication: Long-term visual and neurological correlation

PurposeTo describe MRI and DWI spectrum of brain and optic pathway changes in cases who survived acute methanol poisoning and explore whether there is correlation between imaging features and long-term visual and neurological sequelae. Materials and methodsWe retrospectively reviewed the conventional MRI and DWI of 58 consecutive patients with methanol poisoning. All patients were examined in the chronic phase. ResultsOptic nerve enhancement and atrophy were detected in 33 cases (56.9%). Degree of optic nerve atrophy correlated well with cupping and time lag since initial exposure to methanol. Bilateral putamen necrosis was present in 45 cases (77.6%), 19 showed asymmetrical involvement, and caudate was involved in 6 cases. Asymmetrical necrosis and caudate involvement were correlated with higher grade of neurological deficit. Twenty-one cases (36.2%) showed combination of bilateral putamen necrosis and optic nerve enhancement. Subcortical white matter high SI was detected in 25 patients (43.1%). DWI clearly depicted putamen necrosis with non-restricted pattern. ConclusionSpectrum of residual MRI Findings in patients who survived methanol poisoning included bilateral optic nerve atrophy and enhancement, bilateral putamen and caudate necrosis as well as subcortical white matter high SI at T2WI. Diffusion WI did not have additional value in chronic stage.

‘Why are my diabetes symptoms getting worse?’

During a routine follow-up visit, a 15-year-old male with type 1 diabetes has complained of decreased visual activity and worsening of his polydipsia and polyuria. His past medical history included being diagnosed for type 1 diabetes at the age of eight years and under poor control due to lack of parental supervision. His review of systems was negative for chest pain, claudication and headache. His family history included type 2 diabetes in his paternal grandmother who suffered a vision loss attributed to it. His physical examination showed bilateral mild optic nerve atrophy. There was no thyromegaly. Tanner staging was 4. Laboratory testing showed haemoglobin A1c of 12.8% and negative urine microalbumin. The possibility of diabetes complications affecting the eyes and kidneys was considered, although it was unlikely due to the relatively short duration of diabetes. Ophthalmology consultation confirmed the bilateral optic nerve atrophy without any diabetic retinopathy. This prompted consideration of Wolfram (DIDMOAD) syndrome that consists of diabetes insipidus, diabetes mellitus, optic nerve atrophy and deafness. Extensive laboratory work-up including water deprivation test confirmed the diagnosis of diabetes insipidus. The patient was started on DDAVP (desmopressin) therapy; his polydipsia and polyuria resolved. He started complying better with his diabetes care. Genetic testing showed a mutation in the WFS1 gene confirming the diagnosis of Wolfram syndrome type 1. Auditory testing did not show any hearing deficit. The patient and family were sent for genetic counselling. The aetiology and prognosis of different organ involvement of the syndrome were explained, including blindness, deafness and urinary dysfunction as well as the usual prognosis of diabetes. Wolfram syndrome is an autosomal recessive neuro-endocrine degenerative disorder.1 The syndrome is also known as DIDMOAD as mentioned above. The first and major aspect of Wolfram syndrome is a persistent hyperglycaemia that is insulin dependent in a young child most commonly diagnosed as type 1 diabetes.1, 2 Other organ involvement may start occurring later and may present at different times in life.3 Optic nerve atrophy is often the next sign to appear after diabetes.3, 4 Diabetes insipidus affects almost 70% of patients with this syndrome while deafness occurs in around 65%.4 Other conditions that may occur with this syndrome include hypogonadism, urinary tract problems and neuropsychiatric disorders.4 Many cases of Wolfram syndrome may remain misdiagnosed as type 1 diabetes mellitus.5 Some patients may be misdiagnosed with complications of diabetes due to renal and ophthalmic symptoms.6 Diabetes complications, however, are extremely rare in paediatric diabetes patients. Genetically, there are two types of Wolfram syndrome. Type 1 is the most common type (90%) and is due to mutations in the WFS1 gene. This gene provides instructions for producing a protein called wolframin that is thought to regulate the amount of calcium in cells.1, 4 Wolframin's function is important to produce functional proinsulin.4 WFS1 gene mutations lead to the production of a wolframin protein that has reduced or absent function which triggers apoptosis of beta cells in the pancreas causing diabetes and in the optic nerve leading to blindness.1, 4 Wolfram syndrome type 2 is caused by another mutation in the CISD2 gene which causes the production of a defective protein in the mitochondria that leads to its death.4 When multiple organ involvement is seen in young patients with diabetes, certain syndromes should be considered including Wolfram syndrome or mitochondrial disorders.

Wolfram Syndrome: A Genetic Analysis of 2 Brothers

ABSTRACT Objective: Wolfram syndrome (WS) is a rare, autosomal recessive, progressive disease associated with considerable morbidity, even for heterozygous individuals. Our aim was to describe the cases of 2 brothers with WS and emphasize the importance of this syndrome as a differential diagnosis for autoimmune type 1 diabetes. Methods: Two cases of WS were studied by reviewing medical files and performing clinical and imaging examinations and laboratory tests, including WFS1 gene sequencing. Results: The patients were 2 brothers who were both diagnosed with early onset diabetes mellitus (DM) and were found to have bilateral optic nerve atrophy during screening for chronic complications. In investigating other manifestations of the syndrome, both brothers were found to have diabetes insipidus (DI), moderate hypoacusis, and urinary tract alterations. In addition, there were personal and family histories of psychiatric problems. WS was confirmed through genetic sequencing by a homozygous mutation of the WF...

The Expanding MEGDEL Phenotype: Optic Nerve Atrophy, Microcephaly, and Myoclonic Epilepsy in a Child with SERAC1 Mutations.

The inborn errors of metabolism associated with 3-methylglutaconic aciduria are a diverse group of disorders characterized by the excretion of 3-methylglutaconic and 3-methylglutaric acids in the urine. Mutations in several genes have been identified in association with 3-methylglutaconic aciduria. We describe a patient of Saudi Arabian descent with 3-methylglutaconic aciduria, sensorineural hearing loss, encephalopathy, and Leigh-like pattern on MRI (MEGDEL syndrome), as well as developmental delay and developmental regression, bilateral optic nerve atrophy, microcephaly, and myoclonic epilepsy. The patient had an earlier age of onset of optic atrophy than previously described in other MEGDEL syndrome patients. Whole exome sequencing revealed two loss-of-function mutations in SERAC1 in trans: c.438delC (p.T147Rfs*22) and c.442C>T (p.R148X), confirmed by Sanger sequencing. One of these mutations is novel (c.438delC). This case contributes to refining the MEGDEL phenotype.

Bilateral total optic atrophy due to transdermal methanol intoxication

In this case report, we document a 54-year-old woman with total bilateral optic nerve atrophy after local application of methanol containing spirit. Almost all the reported cases of methanol intoxication in the literature are caused by oral ingestion. In this rare case, we present transdermal absorption of methanol that may cause irreversible blindness in addition to intracerebral lesions.