Cerebroretinal Microangiopathy Research Articles

Neurological Improvement in a Patient with Cerebroretinal Microangiopathy with Calcifications and Cysts-1 Treated with Bevacizumab

Neurological Improvement in a Patient with Cerebroretinal Microangiopathy with Calcifications and Cysts-1 Treated with Bevacizumab

Coats plus syndrome: a rare cause of severe gastrointestinal tract bleeding in children \u2013 a case report

BackgroundCoats plus syndrome, cerebroretinal microangiopathy with calcifications and cysts, is a rare disease with autosomal recessive pattern occurring due to a mutation in CTC1, encoding conserved telomere maintenance component 1, gene. Besides retinal involvement, abnormalities in brain and osteopenia, serious life-threatening bleeding in gastrointestinal tract and portal hypertension can be observed.Case presentationA 6-year-old girl with Coats plus syndrome presented to the pediatric emergency department with vomiting blood and blood in stool. An upper and lower gastrointestinal endoscopy revealed esophageal varices and vascular telangiectasia in the pyloric antrum, duodenum, and colon. She received palliative care and the bleeding was stopped after receiving intravenous octreotide. She then was followed in the pediatric gastroenterology, neurology, and ophthalmology clinics. She was later hospitalized and admitted to the intensive care unit as she continued to have intermittent gastrointestinal system bleeding. She eventually died due to severe gastrointestinal system bleeding.ConclusionsCoats plus syndrome can lead to life-threatening gastrointestinal bleeding and portal hypertension. As Coats plus syndrome is quite rare, there is little published data on this syndrome. This report presents a case of Coats plus syndrome as a rare cause of gastrointestinal bleeding and portal hypertension.

Heterozygous CTC1 Variants in Acquired Bone Marrow Failure

Germ line (GL) alterations of telomerase machinery genes may lead to inherited telomeropathies, but recent analysis of large control populations revealed that some of the previously assumed pathologic variants are present in comparable frequencies in healthy individuals. Pathogenic telomerase gene variants can be found, but are rare in idiopathic aplastic anemia (AA) and are associated with excessive telomere attrition. Previously, in a cohort of patients with MDS, pathogenic germ line variants of telomerase genes were very extremely rare.Recently a patient with bone marrow failure and liver cirrhosis presented with a biallelic CTC1 gene mutation. CTC1 is a member of the CTC complex, located on Chr 17p13.1, and critical for telomere replication. GL alterations of this gene were found to cause inherited disease, including Coats plus (CP), dyskeratosis congenital (DC) and cerebroretinal microangiopathy with calcifications and cysts (CRMCC) in a compound heterozygous manner. Our patient (age 28) had compound heterozygous CTC1 germline mutations (p.Lys242Leufs*41 and p.Cys985del) resulting in early childhood presentation of DC, subsequent severe AA at the age of 19, and a significant shortening of telomeres. Both parents as confirmed CTC1 variant carriers showed normal blood counts.Based on this index case and literature reports, manifest CTC1 diseases follow a recessive trait, however, but it is possible that heterozygous carriers may indeed have also an increased, albeit attenuated risk of BMF leading to a later manifestation or incomplete penetrance. To test this possible scenario we screened a cohort of acquired BMF (n=538) with AA/PNH (172), MDS/AML (n=366), with deep NGS of all coding regions of CTC1. In total, we identified 10 heterozygous CTC1 variants in 10 unrelated patients (8 AA/PNH and 2 MDS); 4/10 variants (1 stop gain R1202X and 3 frameshift deletions D405fs, P999fs, E454fs) were fulfilled the criteria of Tier-1 lesions and were found in AA/PNH patients (4/172, 2.3%), The remaining 6 missense variants were of uncertain significance or likely benign(Tier-2), 2 of which (H1092G and E1136K) were found in a compound heterozygous configuration in a AA/PNH patient. K438N, as a novel missense variant, was recurrently present in 2 MDS pts. Given the expected frequency of the CTC1 variants found in controls (104/33370, 0.3%), CTC1 variants appear to be enriched in AA/PNH subgroup (p<0.001). Of note is that none of the carriers of pathogenic CTC1 mutations showed any physical signs of inherited congenital BMF syndromes or any family history of leukemia, BMF and any other cancers. Interestingly, patients with sAA/PNH syndrome and biallelic CTC1 variant eventually evolved to MDS, while the other monoallelic CTC1 carriers showed stable disease and responsed to immunosuppression. Flow cytometric telomere length measurement (adjusted for age) showed a markedly shortened telomere in the index case, as well as 1 SAA case carrying biallelic CTC1 variants and 1 AA case with co-concurrent POT1 and CTC1 variants when compared with age matched controls. A significant difference was seen when comparing telomere length between CTC1 variants carriers and age-matched normal controls, while no difference was seen among CTC1 variants carriers, AA/PNH group without any variants.Because of the curious co-incidence of heterozygous CTC1 variants and AA/PNH, we further analyzed this subgroup for the presence of other telomerase gene mutations, 11/172 Tier-1 variants, while 6 Tier-1 GLVs detected in MDS. Most frequent SNVs were found in POT1 with 5/172 (3%) in AA/PNH and 3/366 (0.8%) in MDS/AML. Notably, in one AA/PNH patient POT1 stop gain variant (Q364X) was co-concurrent with CTC1 heterozygous frame shift deletion (P999fs). The enrichment of variants in TELO-related genes in AA/PNH subgroup was found in comparison to MDS/AML (p<.01) and ExAC database controls (p<.01). Further clinical phenotype analysis indicated that 3 AA/PNH cases harboring POT1, TINF2 and TERT Tier-1 variants had family history of cancer. Family history of cancer was also found in a MDS patient with a TINF2 variant.In sum, our results indicate that heterozygous CTC1 variants were associated with otherwise typical AA with clonal outgrowth of PNH clone and the presence of this variant does not seem to preclude response to immunosuppression. DisclosuresMaciejewski:Ra Pharmaceuticals, Inc: Consultancy; Ra Pharmaceuticals, Inc: Consultancy; Apellis Pharmaceuticals: Consultancy; Apellis Pharmaceuticals: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) or "Coats plus": when peripheral retinal vasculature signals neurologic disease

Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) or "Coats plus": when peripheral retinal vasculature signals neurologic disease

Retinopathy and bone marrow failure revealing Coats plus syndrome

The inherited bone marrow failure syndromes (IBMFS) are a group of clinically heterogeneous disorders in which at least one hematopoietic cell lineage is significantly reduced in number.1 Dyskeratosis congenita (DC),...

Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) or “Coats Plus”: when peripheral retinal vasculature signals neurologic disease

An 8-month-old girl presented with vitreous hemorrhage, peripheral retinal arteriovenous anastomosis, and hypoplasia of the thumb. Magnetic resonance imaging of the brain showed multiple hyperintensities, cysts, and calcifications in the white matter. DNA testing showed a mutation in one allele of the CTC gene, supporting the diagnosis of cerebroretinal microangiopathy with calcifications and cysts (CRMCC), or Coats plus disease, despite which designation this condition can present without subretinal exudate. In infants with peripheral retinal vascular disease, neuroimaging can identify the characteristic abnormalities of CRMCC.

Identification of novel SNORD118 mutations in seven patients with leukoencephalopathy with brain calcifications and cysts.

Leukoencephalopathy with brain calcifications and cysts (LCC) is neuroradiologically characterized by leukoencephalopathy, intracranial calcification, and cysts. Coats plus syndrome is also characterized by the same neuroradiological findings together with defects in retinal vascular development. Indeed, LCC and Coats plus were originally considered to be the same clinical entity termed cerebroretinal microangiopathy with calcifications and cysts, but evidence suggests that they are genetically distinct. Mutations in CTS telomere maintenance complex component 1 (CTC1) and small nucleolar RNA, C/D box 118 (SNORD118) genes have been found to cause Coats plus and LCC, respectively. Eight unrelated families with LCC were recruited. These patients typically showed major neuroradiological findings of LCC with no signs of extra-neurological manifestations such as retinal abnormality, gastrointestinal bleeding, or hematological abnormalities. SNORD118 was examined by Sanger sequencing in these families. Seven out of eight probands carry compound heterozygous mutations, suggesting that SNORD118 mutations are the major cause of LCC. We identified a total of eight mutation, including four that were novel. Some of the variants identified in this study present heterozygously in public databases with an extremely rare frequency (<0.1%). Biallelic SNORD118 mutations were exclusively found in most unrelated families with LCC.

A Novel Homozygous CTC1 Germline Mutation Associated with Bone Marrow Failure

Iron deficiency in young adult males is rare and necessitates prompt investigations. Here we describe a previously healthy 22-year-old male suffering from gastrointestinal bleeding leading to iron deficiency anemia and explained by a constitutional disease. His diagnosis was obtained after detecting a homozygous CTC1 mutation in his germline DNA. Conserved telomere maintenance component 1 (CTC1) is a part of the conserved telomere-associated complex (CST) participating in telomere replication. CST seems to have a role in resolving replication stress also in non-telomeric regions, but little is known about the exact mechanisms. Biallelic, typically compound heterozygous mutations in CTC1 are known to cause cerebroretinal microangiopathy with calcifications and cysts(CRMCC), which is considered as a telomere disease. It is a highly pleiotropic multi-organ disease characterized by abnormalities e.g. in the brain, retina, intestinal vasculature, as well as bone marrow failure (BMF). Some CRMCC patients have dyskeratosis congenita (DC) -like skin, nail, mucosal, and hair changes. Most patients are diagnosed in early childhood and die before teens. To date 37 patients with CRMCC and CTC1 mutations have been reported.The patient was referred to hematology due to iron deficiency anemia with coinciding thrombocytopenia. He also had a notable lymphopenia but no tendency for viral infections or other signs of immunodeficiency. Imaging revealed a patent umbilical vein, widened portal vein, and hepatosplenomegaly without parenchymal changes or lymphadenopathy. Gaucher's disease was excluded by glucocerebrosidase and genetic tests. Histology of a liver biopsy was normal. Based on these findings an idiopathic portal hypertension was diagnosed. Endoscopy revealed gastric antral vascular ectasia. The bone marrow was hypoplastic and pancytopenia persisted after supplementation with iron. He had no known family history of BMF. The patient's telomere length analyzed by a semi-quantitative PCR-test was within the normal range compared to healthy controls of the same age group. We then sequenced the patient's germline exome. Roche MedExome kit was used to target the coding regions of the genome and sequencing conducted using an Illumina HiSeq1500 sequencer. The quality of the data was assessed and the sequence data analyzed using an in-house developed analysis pipeline. The mutation analysis was targeted to genes previously reported to cause immune deficiencies, myelodysplastic syndrome and BMF. The average sequence coverage was 59x, translating into 95% of the exome being covered with a minimum of 20x.Common polymorphisms were excluded from the analysis. The patient was identified to carry a homozygous variation in CTC1 exon 12; c.1994T>G, p.V665G (rs199473676). The variant has previously been reported pathogenic, but all previously reported cases of p.V665G are compound heterozygous (in the majority of cases V665G and a frameshift mutation). The minor allele frequency for this variant in Finns is 0.0015 (10/6612 alleles) and 0.0001 (13/120608) in total (ExAC database) suggesting this mutation is a Finnish founder mutation. We validated the finding by capillary sequencing. The variant was detected heterozygous in both parents ruling out a larger deletion and verifying the mode of inheritance. A healthy sister did not carry the mutation. Identification of CTC1 p.V665G homozygosity raised a high suspicion of CRMCC and further investigations were indicated. Retinal examination as well as brain MRI/MRA revealed multiple lesions characteristic for CRMCC.This is the first report on homozygous CTC1 p.V665G and the second describing CTC1-homozygosity associated with CRMCC, strengthening the disease-causality of biallelic missense mutations in CTC1. The identification of a homozygous CTC1 p.V665G may also open new prospects for studying the effects of the mutation. Our case shows the importance and capacity of new genomic techniques in clinical management, as well: The patient's primary phenotype with iron deficiency anemia, thrombopenia and hepatosplenomegaly could have been explained by only an idiopathic portal hypertension. However, with exome sequencing we were able to reveal a more complex disease entity with major impact on patient's future care and genetic counseling, highlighting the value of germline sequencing in modern diagnostics. DisclosuresNo relevant conflicts of interest to declare.

Cerebro-retinal microangiopathy with calcifications and cysts due to recessive mutations in the CTC1 gene

Cerebro-retinal microangiopathy with calcifications and cysts (CRMCC) or Coats plus syndrome is a pleiotropic disorder affecting the eyes, brain, bone and gastrointestinal tract. Its primary pathogenesis involves small vessel obliterative microangiopathy. Recently, autosomal recessively inherited mutations in CTC1 have been reported in CRMCC patients. We herein report an adolescent referred to our hospital following new seizures in a context of an undefined multisystem disorder. Cerebral imaging disclosed asymmetrical leukopathy, intracranial calcifications and cysts. In addition, he presented other typical CRMCC features i.e. a history of intrauterine growth retardation, skeletal demineralization and osteopenia, bilateral exudative vitreo-retinopathy reminiscent of Coats disease, recurrent gastrointestinal hemorrhages secondary to watermelon stomach and variceal bleeding of the esophagus due to idiopathic portal hypertension and telangiectatic and angiodysplasic changes in the small intestine and colon, and anemia due to recurrent bleeding and bone marrow abnormalities. The patient was diagnosed with Coats plus syndrome. CTC1 gene screening confirmed the diagnosis with the identification of heterozygous deleterious mutations. CRMCC due to CTC1 mutations has a broad clinical expressivity. Our case report illustrates the main possible associated phenotypes and their complications, demonstrating the need for a careful etiological search in order to initiate appropriate therapeutic and preventive measures.

Adult-Onset Genetic Leukoencephalopathies. Focus on the More Recently Defined Forms.

Inherited white matter (WM) disorders include a heterogenous group of disorders affecting brain white matter and associated with myelin, axonal and glial cells or vascular pathology. Often a wide range of overlapping neurological manifestations possibly associated with variable systemic involvement are found in these disorders making clinical diagnosis challenging. Advances in molecular genetics enabled the identification of the responsible genes of an increasing number of previously undefined forms. This review focuses on genetic leukoencephalopathies with exclusive adulthood presentation, most of which have an autosomal dominant inheritance. The most common forms are related to vascular pathology, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), COL4A1-related leukoencephalopathy, retinal vasculopathy with cerebral leukodystrophy (RVCL), and polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). Also cerebroretinal microangiopathy with cysts and calcifications (CRMCC), which presents a prevalent infantile onset, will be detailed because of the vascular based myelin damage and the recent genetic characterization. Other adult onset (AO) leukoencephalopathies, such as the recently genetically defined hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS), adult-onset autosomal dominant leukodystrophy (ADLD) due to LMNB1 duplication, adult polyglucosan body disease (APBD), and fragile X-associated tremor/ataxia syndrome (FXTAS) will be detailed shortly. Short notes on the clinical and MRI features of late onset variants of the classical infantile-onset leukodystrophies mostly related to metabolic disorders will also be given. Finally, palliative, curative and experimental treatment options are here summarized.

Update on several/certain adult-onset genetic leukoencephalopathies: clinical signs and molecular confirmation.

Adult-onset leukoencephalopathies are clinically and pathologically heterogeneous diseases, characterized by overlapping clinical and neuroradiological features and a difficult diagnostic process. Nevertheless, knowledge of the metabolic and genetic basis of leukoencephalopathies is constantly increasing. This article provides an overview of currently known leukoencephalopathies in adulthood, emphasizing, in addition to the classical forms, their atypical clinical presentations. In particular, we review the clinical spectrum and the molecular pathogenesis of certain adult-onset leukoencephalopathies, including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), cerebroretinal microangiopathy with calcifications and cysts (CRMCC), hereditary diffuse leukoencephalopathy with spheroids (HDLS), fragile X-associated tremor/ataxia syndrome (FXTAS), vanishing white matter disease (VWM), autosomal dominant leukodystrophy due to lamin B1 duplication (ADLD), and vascular leukoencephalopathy mapping to chromosome 20q13.

Leukoencephalopathy, cerebral calcifications and cysts: a family study.

We present a clinical, neuro-radiological and genetic study on a family with members suffering from an autosomal dominantly inherited syndrome characterised by epilepsy, cerebral calcifications and cysts, bone abnormalities; progressive neuro-cognitive deterioration and paranasal sinusitis. This syndrome shares several features with leukoencephalopathy with calcifications and cysts also called Labrune syndrome and the condition of cerebroretinal microangiopathy with calcifications and cysts (CRMCC; Coats plus syndrome). Genetic studies in this family did not reveal mutations in the CTC1 gene defected in CRMCC. We interpret our results as those supporting recent findings that despite clinical similarities, late-onset Labrune and Coats plus syndrome might be distinct entities. This family may have Labrune syndrome or a yet unclassified entity; exploration of similar cases could help classifying this one, and related conditions.

Hallazgos por neuroimagen de la microangiopatía cerebral retiniana con calcificaciones y quistes

Cerebroretinal microangiopathy with calcifications and cysts is a rare condition characterized by brain, retinal and bone anomalies, as well as a predisposition to gastrointestinal bleeding. There are few reported cases of this condition in adults, among whom the incidence is low. Neuroimaging findings are characteristic, with bilateral calcifications, leukoencephalopathy and intracranial cysts. The purpose of this article was to do a literature survey and illustrate two cases diagnosed with the aid of neuroimaging.

EVER‐Acta lecture: Telomere maintenance and retinal vascularisation

AbstractAbnormal development of the retinal vasculature is an important cause of vision loss in infancy, childhood and, occasionally, in adult life. In addition to retinopathy of prematurity from exposure to oxygen after preterm birth, several genetic defects affecting retinal vascularization have recently been discovered, affecting either Wnt signaling or telomere maintenance. The canonical norrin–beta‐catenin pathway of Wnt signaling is deranged by mutations in frizzeld‐4 (FZD4), low density lipoprotein receptor‐related protein 5 (LRP5), norrin (NDP) and other genes. These lead to vascular leakage, vitreoretinal traction or both in Coats’ disease, familial exudative vitreoretinopathy (FEVR), Norrie’s disease and osteoporosis‐pseudoglioma syndrome. Mutations in telomeric repeat‐binding factor 1‐interacting nuclear factor 2 (TINF2) and CTS telomere maintenance complex component 1 (CTC1) in Revesz syndrome and cerebroretinal microangiopathy with calcifications and cysts (CRMCC) can even cause retinal angiomas. Wnt signaling initially was the suspect for them as well, because all six diseases share more or less widespread retinal avascularity as a hallmark. Indeed, a link between the two pathways is still possible. The manifestations of the telomere‐related syndromes are more protean than those of Wnt‐related ones, which have no other significant systemic findings than osteoporosis if LRP5 is mutated. The former may lead to a cerebral and intestinal vasculopathy or hepatopathy, all of which can be fatal, and to skin and hair abnormalities. Milder forms can escape diagnosis until adulthood. It is useful to recognize these genetic vasculopathies. Genes for cases which still go unexplained remain to be discovered.

Adult-onset leukoencephalopathy, brain calcifications and cysts: a case report

IntroductionLeukoencephalopathy, brain calcifications and cysts, known as Labrune syndrome, is a rare syndrome. The etiology is unknown; in some cases it is difficult to differentiate from Coats plus syndrome and diagnosed as cerebroretinal microangiopathy with calcifications and cysts. We present the case of a patient with adult leukoencephalopathy, brain calcifications and cysts and discuss recently described entities in view of the relevant literature.Case presentationA previously healthy 19-year-old Chinese man presented with weakness of his right limbs that rapidly worsened over a short interval. Computed tomography and magnetic resonance imaging showed numerous low-density cysts, calcifications, and abnormal signal change of white matter. A visual field examination showed irregular visual field defects in both eyes. A neuro-ophthalmologic examination did not find evidence of Coats retinopathy. A larger excisional biopsy was carried out and a diagnosis of leukoencephalopathy, brain calcifications and cysts was confirmed.ConclusionsWe present an example of adult-onset leukoencephalopathy, brain calcifications and cysts and have expanded the clinical spectrum of features associated with this syndrome. Previous reports have not, to the best of our knowledge, previously reported visual field defects. Based on the latest findings, we believe that leukoencephalopathy, brain calcifications and cysts and Coats plus syndrome are genetically distinct entities.

Cerebroretinal Microangiopathy With Calcifications and Cysts Associated With CTC1 and NDP Mutations

Mutations in the conserved telomere maintenance component 1 (CTC1) gene were recently described in Coats plus syndrome and in cerebroretinal microangiopathy with calcifications and cysts. Norrie disease protein (NDP) gene was found mutated in Norrie disease, in Familial Exudative Vitreoretinopathy, and in Coats syndrome. Here we describe a boy affected by Norrie disease who developed typical features of cerebroretinal microangiopathy with calcifications and cysts. Direct sequencing of the CTC1 and NDP genes in this patient shows the presence of compound heterozygosity for 2 mutations in CTC1 (c.775G>A, pV259M and a novel microdeletion c.1213delG) and a missense mutation in the NDP gene (c.182T>C, p.L61P). Based on these genetic findings and on the expression of both genes in endothelial cells, we postulate that microangiopathy might be a primary underlying pathologic abnormality in cerebroretinal microangiopathy with calcifications and cysts. This hypothesis is further supported by magnetic resonance imaging (MRI) data showing multiple minute calcifications in the deep gray nuclei and in terminal arteriolar zones.

Recognizable phenotypes associated with intracranial calcification

In this observational study, we adopted a systematic approach to the radiological phenotyping of disorders associated with intracranial calcification, with the aim of determining if characteristic patterns could be defined as an aid to the future diagnosis of known conditions and the identification of new disorders. A cranial imaging-based scoring system was devised using both computed tomography and magnetic resonance imaging data. Patients were grouped into diagnostic categories where a definitive molecular diagnosis was known, or where the clinical and radiological features suggested a specific diagnosis. For patients in whom the diagnosis was unknown, subgroups were defined according to shared radiological features. Data on 244 scans from 119 patients were analysed. A specific diagnosis was available for 59 patients (31 males, 28 females; median age 50 mo, range 1 wk to 54 y). These were as follows (number of patients in brackets): Aicardi-Goutières syndrome (33), cerebroretinal microangiopathy with calcification and cysts (10), band-like calcification with simplified gyration and polymicrogyria (6), COL4A1-related disease (3), Degos disease (2), Krabbe disease (2), Alexander disease (1), mitochondrial disease (1), and tetrasomy 15 (1). In 60 patients the aetiology was unknown. Within this group, subsets demonstrating shared characteristics suggestive of a specific calcification phenotype could be identified. This study confirms the value of a systematic approach to radiological phenotyping of disorders associated with intracranial calcification.

Progressive cerebroretinal microangiopathy with calcifications and cysts syndrome: An unusual cause of complex partial seizure

PROGRESSIVE CEREBRORETINAL MICROANGIOPATHY syndrome is characterized by cerebral calcification and cyst formation (CRMCC), as defined in recent years,1 and is described in the published reports as Coats plus syndrome, Labrune syndrome and leukoencephalopathy calcification and cysts (LCC) syndrome.2 Cerebral, ophthalmic, skeletal, intestinal involvement can be seen. CRMCC determined in late adolescence is limited. Autosomal recessive inheritance is reported.3 In the majority of patients, neurological findings showing progression have been reported, such as spasticity, dystonia, ataxia and loss of cognitive abilities. Imaging findings with laboratory data should support the diagnosis.4 The case presented here is of a 20-year-old male patient whose indications began in late adolescence and were defined as CRMCC characterized by central nervous system involvement. The patient had a history of febrile convulsions at the age of 2, and until 20 years old had suffered no seizures. He started to have complex partial seizure (CPS) with an aura of loss of speech and extremity numbness followed by extremity spasms accompanied by spasm of the head and neck area, versive rotation movements and manual automatisms after 20 years of age. Familial inheritance was not shown. The neurological and ophthalmological examination was normal. There were no psychiatric, psychological or behavioral problems besides CPS. Memory disturbance due to left temporal lobe dysfunction was determined by the Wechsler Memory Scale (WMS) psychometric tests. Under observation in the video electroencephalography monitorization unit, CPS were seen three times. Seizures lasting up to 1 min were observed, before the seizure, showing a defining aura of loss of speech and numbness on the right side of the body, while during the seizure he had a behavioral arrest, his head was versive turned to the right and there were oral-alimentary and bilateral manual automatisms. Spike, sharp and slow wave activities were observed starting from the left frontal region and emitting to the temporal region during the seizure. For this reason, the seizure from the left frontal region and spread to the left temporal region was concluded. Computed tomography showed multiple calcified foci in the cyst wall, basal ganglia, thalami and cerebral white matter. Magnetic resonance (MR) imaging revealed signal abnormalities in the cerebral white matter, and a right thalamo-caudate cyst and a smaller pontine cyst. There was no restriction of diffusion-weighted MR images. MR spectroscopy demonstrated minimal increase in the choline peak, mild decrease in the N-acetylaspartate peak, and a lactate peak. Serology positive data were not determined. CRMCC cases generally show indications at an early age and the number of cases determined in late adolescence and older is relatively limited. Cases may present with different clinical tables related to the system involvement. To the best of our knowledge, cases of CRMCC-related complex partial seizures have not been reported. In the radiological imaging data of CRMCC syndrome as leukoencephalopathy (demyelinization and white matter edema), calcification and cyst formation were found. It is a syndrome which may accompany retinal microangiopathy. A differential diagnosis of CRMCC should be considered for cases presenting with CPS and radiological imaging findings. The patient gave the authors written informed consent to publish this report. We would like to thank Patricia E. Miller, University of Rochester Medical Center, NY, USA.

Response to the article by Linnankivi et al., entitled ‘Cerebroretinal microangiopathy with calcifications and cyst, Revesz syndrome and aplastic anemia’

Response to the article by Linnankivi et al. , entitled ‘Cerebroretinal microangiopathy with calcifications and cyst, Revesz syndrome and aplastic anemia’

Cerebroretinal microangiopathy with calcifications and cysts, Revesz syndrome and aplastic anemia

Cerebroretinal microangiopathy with calcifications and cysts, Revesz syndrome and aplastic anemia