Long-term follow-up of a case of choroidal neovascularization secondary to reticular pigmentary retinal dystrophy / Seguimento de longo-prazo de um caso de neovascularização de coroide secundária à distrofia reticular pigmentar da retina

ABSTRACT Reticular pigmentary retinal dystrophy, also known as Sjögren's reticular dystrophy, is a rare condition characterized by macular lesions with a reticular pattern, which are best seen on fluorescein angiogram. Choroidal neovascularization secondary to this type of dystrophy is even less common. This report describes a case of reticular pigmentary retinal dystrophy with vision loss due to neovascular membrane, which responded well to treatment with anti-vascular endothelial growth factor.

RESUMO A distrofia reticular pigmentar da retina, também conhecida como distrofia reticular de Sjögren, é uma doença rara, caracterizada por lesões maculares com um padrão reticular, que são mais bem visualizadas na angiografia com fluoresceína. A neovascularização de coroide secundária a este tipo de distrofia é ainda menos comum. Este relato descreve um caso de distrofia reticular pigmentar da retina, com perda de visão devido à membrana neovascular, que respondeu bem ao tratamento com fator de crescimento endotelial antivascular.

Definición diagnóstica en una familia con malattia leventinese en Colombia / Diagnostic definition of malattia leventinese in a family from Colombia

Resumen La malattia leventinese es una enfermedad hereditaria autosómica dominante, cuyos síntomas se inician entre la segunda y la cuarta décadas de la vida. Se caracteriza por la aparición de drusas localizadas entre el epitelio pigmentario de la retina y la membrana de Bruch; suele reducir la visión drásticamente y progresar a ceguera. La variante patogénica p.Arg345Trp en el gen EFEMP1 se ha asociado con esta enfermedad. Se presenta aquí la caracterización clínica y molecular de una familia con malattia leventinese mediante un manejo integral que involucró a oftalmólogos, pediatras y genetistas, lo que es de gran importancia, ya que el fenotipo de esta enfermedad suele confundirse con la degeneración macular. A todos los individuos de la familia se les hizo la evaluación oftalmológica con imágenes diagnósticas de retina y extracción de ADN a partir de una muestra de sangre periférica. Todos los exones del gen EFEMP1 se amplificaron y secuenciaron. La variante patogénica p.Arg345Trp se identificó en los individuos afectados. Este es el primer reporte de malattia leventinese en una familia con la variante patogénica p.Arg345Trp en Colombia. El diagnóstico molecular de las distrofias retinianas es fundamental para diferenciar este tipo de enfermedades.

Abstract The malattia leventinese is an autosomal dominant inherited disease whose symptoms appear between the second and fourth decades of life. It is characterized by the appearance of drusen located between the retinal pigment epithelium and the Bruch membrane. It is usually associated with low vision and may progress to blindness. The pathogenic variant p.Arg345Trp in the EFEMP1 gene has been associated with this disease. We characterized clinically and molecularly a family with malattia leventinese using a comprehensive approach that involved ophthalmologists, pediatricians, and geneticists. This approach is of great importance since the phenotype of this disease is often confused with macular degeneration. All family members underwent ophthalmological evaluation and DNA extraction from a peripheral blood sample. All exons of the EFEMP1 gene were amplified and sequenced. The pathogenic variant p.Arg345Trp was identified in affected individuals in this family. This is the first report of malattia leventinese in a family with the p.Arg345Trp pathogenic variant in Colombia. The molecular diagnosis of retinal dystrophies is essential to differentiate this type of pathology.

Comparison study of whole exome sequencing and targeted panel sequencing in molecular diagnosis of inherited retinal dystrophies / 北京大学学报(医学版)

OBJECTIVE@#To evaluate and compare whole exome sequencing (WES) and targeted panel sequencing in the clinical molecular diagnosis of the Chinese families affected with inherited retinal dystrophies (IRDs).@*METHODS@#The clinical information of 182 probands affected with IRDs was collected, including their family history and the ophthalmic examination results. Blood samples of all probands and their relatives were collected and genomic DNA was extracted by standard protocols. The first 91 cases were subjected to the WES and the other 91 cases were subjected to a specific hereditary eye disease enrichment panel (HEDEP) designed by us. All likely pathogenic and pathogenic variants in the candidate genes were determined by Sanger sequencing and co-segregation analyses were performed in available family members. Copy number variations (CNVs) detected by HEDEP were further validated by multiplex ligation-dependent probe amplification (MLPA). As PRGR ORF15 was difficult to capture by next generation sequencing (NGS), all the samples were subjected to Sanger sequencing for this region. All sequence changes identified by NGS were classified according to the American College of Medical Gene-tics and Genomics and the Association for Molecular Pathology (ACMG/AMP) variant interpretation guidelines. In this study, only variants identified as pathogenic or likely pathogenic were included, while those variants of uncertain significance, likely benign or benign were not included.@*RESULTS@#In 91 cases with WES, pathogenic or likely pathogenic variants were determined in 30 cases, obtaining a detection rate of 33.00% (30/91); While in 91 cases with HEDEP sequencing, pathogenic or likely pathogenic variants were determined in 51 cases, achieving the diagnostic rate of 56.04% (51/91), and totally, the diagnostic rate was 44.51%. HEDEP had better sequencing coverage and read depth than WES, therefore HEDEP had higher detection rate. In addition, HEDEP could detect CNVs. In this study, we detected disease-causing variants in 29 distinct IRD-associated genes, USH2A, ABCA4 and RPGR were the three most common disease-causing genes, and the frequency of these genes in Chinese IRDs population was 11.54% (21/182), 6.59% (12/182) and 3.85% (7/182), respectively. We found 43 novel variants and 6 cases carried variants in RPGR ORF15.@*CONCLUSION@#NGS in conjunction with Sanger sequencing offers a reliable and effective approach for the genetic diagnosis of IRDs, and after evaluating the pros and cons of the two sequencing methods, we conclude that HEDEP should be used as a first-tier test for IRDs patients, WES can be used as a supplementary molecular diagnostic method due to its merit of detecting novel IRD-associated genes if HEDEP or other methods could not detect disease-causing va-riants in reported genes. In addition, our results enriched the mutational spectra of IRDs genes, and our methods paves the way of genetic counselling, family planning and up-coming gene-based therapies for these families.

Retinal dystrophies and variants in PRPH2 / Distrofias retinianas e variantes em PRPH2

ABSTRACT - This report presents three patients diagnosed with macular dystrophies with variants in PRPH2. Peripherin-2, the protein of this gene, is important in the morphogenesis and stabilization of the photoreceptor outer segment. Peripherin-2 deficiencies cause cellular apoptosis. Moreover, pathogenic variants in PRPH2 are associated with various diseases, such as pattern, butterfly-shaped pattern, central areolar, adult-onset vitelliform macular, and cone-rod dystrophies as well as retinitis pigmentosa, retinitis punctata albescens, Leber congenital amaurosis, fundus flavimaculatus, and Stargardt disease.

RESUMO - Este relato apresenta três pacientes com diagnóstico de distrofias maculares com mutações no PRPH2. Periferina 2, a proteína deste gene, é importante na morfogênese e estabilização do segmento externo dos fotorreceptores. Deficiências de periferina 2 causam apoptose celular. Além disso, variantes patogênicas no PRPH2 estão relacionadas a diferentes doenças, como distrofia padrão, distrofia padrão em asa de borboleta, distrofia central areolar, distrofia viteliforme do adulto, retinose pigmentar, distrofia de cones e bastonetes, retinite punctata albscens, amaurose congênita de Leber, fundus flavimaculatus e doença de Stargardt.

Sjögren's Reticular Retinal Dystrophy

PURPOSE: To report a rare case of Sjögren's reticular retinal dystrophy. CASE SUMMARY: A 54-year-old male presented with blurred vision and metamorphopsia in both eyes since a few years prior to his initial visit. There was a bilateral reticular network of yellow deposits throughout the posterior pole on fundus examination, which was hyperautofluorescent in fundus autofluorescence photographs. The pigment alterations were more visible with fluorescein angiography, which showed hypofluorescent lesions with hyperfluorescent borders. Spectral-domain optical coherence tomography showed elevations of the outer retina associated with the presence of subretinal hyperreflective material. Based on the conclusive correlation with clinical features, we diagnosed Sjögren's reticular retinal dystrophy. CONCLUSIONS: Sjögren's reticular retinal dystrophy is characterized by its specific pigment changes at the level of clinical manifestations and the retinal pigment epithelium. In cases of Sjögren's reticular retinal dystrophy, close monitoring is required because it has a lifetime risk of choroidal neovascularization.

Síndrome de Bardet-Biedl: série de caso e revisão da literatura / Bardet- Biedl Syndrome: case series and literature revision

Resumo A Síndrome de Bardet-Biedl é uma desordem autossômica recessiva rara, com heterogeneidade clínica e genética. As principais características são retinopatia pigmentar, obesidade, polidactilia, dificuldades de aprendizado, diversos graus de deficiência intelectual, anomalias renais e hipogonadismo. O objetivo desse trabalho é relatar dois casos de síndrome de Bardet-Biedl em pacientes diagnosticados no Instituto Benjamin Constant e fazer uma revisão literária da síndrome. Revisão de prontuário e pesquisa bibliográfica nas bases de dados do PubMed, SciELO, MEDLINE e LILACS. Atualmente não há tratamento para a Síndrome de Bardet-Biedl, mas o diagnóstico precoce é importante para orientar a gestão da criança através de uma avaliação regular da pressão arterial, peso, estudos de imagiologia renais, exames oftalmológicos e apoio psicológico.

Abstract The Bardet-Biedl Syndrome is a rare autosomal recessive disorder with clinical and genetic heterogeneity. Its main characteristics are pigmentary retinopathy, obesity, polydactyly, learning disabilities, various degrees of intellectual disability, renal anomalies and hypogonadism. The objective of this study is to report two cases of the Bardet-Biedl syndrome in patients diagnosed at the Benjamin Constant Institute and to perform a literary review of the syndrome. Review of medical records and bibliographic research were made from the PubMed, SciELO, MEDLINE and LILACS databases. Currently, treatment for the Bardet-Biedl Syndrome does not exist, but early diagnosis is important to guide the child through a regular assessment of blood pressure, weight, renal imaging studies, eye exams and psychological support.

Causes of low vision and blindness in a Turkish adult population: the Izmir eye study

Background: Data from Turkey show that sense organ diseases were the second leading cause of years lost due to disability in 2015. However, there are no reliable data on either the baseline causative disorders of visual impairment or the burden of these disorders on the population in Izmir region. Izmir is the third most populated city of Turkey with a population of approximately 4.2 million. Aim: The purpose of this study was to define the baseline disorders causing low vision and blindness in accordance with World Health Organization criteria in an adult population in Izmir. Methods: We evaluated the ophthalmologic reports of 20 790 people in Izmir, Turkey. Age- and sex-specific causes of low vision and blindness were identified. Results: Bilateral low vision and blindness was detected in 347 people, 172 males and 175 females. For those aged 18–50 years, retinal dystrophies [37%], congenital eye anomalies [14%] and myopic degenerations [13%] were the most common causes. For those aged 50+ years, age-related macular degeneration [21%] was the leading cause. Diabetic retinopathy [17%], corneal opacities [14%], cataract [12%] and glaucoma [9%] were also important. Sex was not a significant determinant. Conclusion: The specific causes of visual impairment vary greatly with age, however, unavoidable retinal pathologies were the predominant causes at all ages

Degeneración marginal de Terrien / Terrien marginal degeneration

La degeneración corneal marginal de Terrien es una enfermedad ocular rara, generalmente bilateral y asimétrica, caracterizada por el adelgazamiento marginal de la córnea. Presentamos una paciente de 58 años quien asistió a consulta por lagrimeo y en la biomicroscopia mostraba adelgazamiento y opacidad marginal circunferencial en 360º con línea bien diferenciada de depósitos lipoideos y vascularización periférica nasal. En las imágenes de Scheimpflug se observó espesor corneal central conservado con adelgazamiento periférico. El mapa paquimétrico mostró valores inferiores en la zona nasal que correspondía con áreas de mayor valor queratométrico en el mapa de curvatura y con el área de mayor adelgazamiento por biomicroscopia. Por las características descritas se trata de una degeneración marginal de Terrien. Esta es una enfermedad de curso lento y progresivo, sin afectación de la córnea central, por lo que su pronóstico, en general, es bueno. Aquellos casos en los que se produce descemetocele o perforación periférica pueden necesitar una queratoplastia periférica lamelar penetrante(AU)

Terrien marginal corneal degeneration is a rare eye disease, generally bilateral and asymmetrical, which is characterized by marginal attenuation of the cornea. Here is a 58 years-old patient, who attended the doctor´s office for lachrymation; the biomicroscopy evinced corneal attenuation and 360º circumferencial marginal opacity with a well differentiated line of lipoid deposits and peripheral nasal vascularization. Scheimpflug camera images showed a preserved central corneal thickness with peripheral attenuation. The pachymetric map showed lower values in the nasal area coinciding with areas of higher keratometric value in the curvature map and with the area of greater attenuation according to biomicroscopy. Due to the described characteristics, it has to do with Terrien´s Marginal Degeneration. This is a slow progressive disease, with no effect for the central cornea, so its prognosis is generally good. In those cases where the disease causes decemetocele or peripheral perforation, the patient may need penetrating lamellar peripheral keratoplasty(AU)

Whole Exome Sequencing in a Korean Child with Joubert Syndrome-related Disorders

Joubert syndrome and Joubert syndrome-related disorders (JSRDs) are rare autosomal recessive or X-linked disorders characterized by cerebellar vermis hypoplasia and a brain stem malformation, which presents as the “molar tooth sign” in magnetic resonance imaging (MRI). JSRDs are a group of clinically heterogeneous conditions that exhibit neurological manifestations and multiple organ involvement. JSRDs are also genetically heterogeneous, and approximately 20 causative genes that account for 45% of JSRDs have been identified. A 7-yr-old boy visited Wonkwang University Sanbon Hospital with the following presentations: no ocular fixation, ataxia, growth retardation, and hypotonia. Physical examination revealed facial dysmorphism, spindle shaped fingers, and height (99 cm) and weight (13 kg) below the third percentile. Ophthalmic examination revealed retinal dystrophy. A diagnosis of JSRDs was made based on clinical and brain MRI findings. We found two heterozygous variants c.2945 G>T; p.Arg982Met (G>T) and c.2216dupA; p.Phe740Valfs*2 (dupA) in AHI1, and a heterozygous c.3973C>T; p.Arg1325Trp (C>T) variant in KIF7 by whole exome sequencing (WES). Genetic analysis on the proband's father revealed that he had both AHI1 variants, but did not have the KIF7 variant, which was inconsistent with autosomal recessive inheritance. Therefore, the G>T variant and C>T variant were presumed to be of “uncertain significance.” Furthermore, one novel dupA variant was interpreted as “pathogenic,” while the second allele was not detected. Caution should be exercised while interpreting the significance of variants detected by WES. In addition, the involvement of genes other than the 20 known ones will require further investigation to elucidate the pathogenesis of JSRDs.

Epidemiologic Aspects of Medical Retirement from the Republic of Korea Army due to Visual Impairment

This study was done to report the epidemiologic characteristics of medical retirement from the Republic of Korea (ROK) Army due to visual impairment and to suggest a practical screening system for the draft. The medical records of 423 eyes of 301 patients who retired from the ROK Army due to visual impairment were reviewed retrospectively between January 2010 and December 2014. The patients were grouped by the presence of trauma, and each group was subdivided by military rank. We analyzed demographic and ophthalmic data, including the etiology of ophthalmologic disease. The etiology was classified into 5 anatomical categories (ocular surface, lens, retina, optic nerve and extraocular visual pathway, and extraocular muscle and orbit), which were then subdivided into the type of disease. The mean age was 24.5 years, and non-traumatic mechanisms accounted for 81.1% (343/423 eyes) of medical retirements. Visual acuity was better in patients without trauma. In enlisted soldiers, disease in the optic nerve and extraocular visual pathway was the most common anatomical category (40.5%), and primary open angle glaucoma (30.8%), retinal dystrophy (18.3%), congenital cataract (14.5%), and retinal detachment (9.7%) were the four most common diseases. Most medical retirements due to visual impairment resulted from non-traumatic mechanisms, even though patients were young. The fundus examination and visual field test would be more useful tools than a conventional vision test for large-scale draft screening for the most common two disease types: primary open angle glaucoma and retinal dystrophy.

Distrofia corneal granular / Granular corneal dystrophy

Las distrofias corneales constituyen un conjunto de enfermedades que presentan, en su mayoría, una baja incidencia y se caracterizan por acúmulo de material hialino o amiloide que disminuyen la transparencia corneal. La distrofia granular es una enfermedad autosómica dominante que presenta opacidades grises en el estroma superficial central de la córnea y se hacen visibles en la primera y segunda décadas de la vida, lo que provoca disminución de la visión más significativa cerca de los 40 años de edad. Presentamos dos casos clínicos de distrofia granular en pacientes hermanos de diferentes sexos, quienes acudieron a la consulta y refirieron visión nublada. El estudio de la historia familiar nos ayuda en el correcto diagnóstico y la biomicroscopia constituye el elemento más importante(AU)

Corneal dystrophies are a group of diseases that mostly have low incidence rates and are characterized by accumulation of hyaline or amyloid material that reduces the corneal transparency. Granular dystrophy is a dominant autosomal disease with gray opacities in the central superficial stroma of cornea, which are visible in the first and second decades of life and leads to significantly reduced vision when going into the 40 years of age. Here are two clinical cases of granular dystrophy in a pair of siblings who went to the doctor's because of blurred vision. The study of the family history helps the physician to reach a right diagnosis and the most important element is biomicroscopy(AU)

Distrofia de la membrana basal epitelial / epithelial basal membrane dystrophy

La distrofia de Cogan es la distrofia corneal anterior más común, frecuente en adultos del sexo femenino, entre 40-70 años de edad. Presentamos un caso de una paciente de 50 años de edad, del sexo femenino, quien refiere visión borrosa, lagrimeo y fotofobia. Al examen de la córnea en lámpara de hendidura se observan imágenes de color grisáceo en forma de huellas dactilares y de mapa. Esta afección es causada por alteraciones de la membrana basal epitelial que provoca la separación parcial o total del epitelio corneal. Generalmente asintomática, es la causa más frecuente de erosión corneal recurrente. Las opciones terapéuticas varían desde lubricantes, soluciones hipertónicas tópicas, lentes de contacto de vendaje, desbridamiento del epitelio central, micropunciones mecánicas o diatermia y fotoqueratectomía con láser excímer(AU)

Cogan's dystrophy is the most common anterior corneal dystrophy in adult females aged 40-70 years of age. Here is a 50 years-old female patient suffering from blurred vision, weeping eyes and photophobia. On examination, grayish images were observed in the form of fingerprints and map. This disease is caused by alterations of the epithelial basal membrane bringing about partial or total removal of the corneal epithelium. Often asymptomatic, it is the most common cause of recurrent corneal erosion. Treatment options range from lubricants, topical hypertonic solutions, bandage contact lenses, central epithelial debridement, mechanical or diathermy micropuncture and excimer laser photokeratectomy(AU)

Two siblings with Bardet-Biedl syndrome caused by mutations in BBS10: the first case identified in Korea

Bardet-Biedl syndrome (BBS) is a rare ciliopathy generally inherited with an autosomal recessive pattern. BBS is characterized by 6 primary features namely retinal dystrophy, obesity, postaxial polydactyly, renal dysfunction, learning difficulties, and hypogonadism and a wide range of secondary features. To date, mutations in 16 genes have been identified as causative factors for BBS. Among them, the BBS1 and BBS10 genes are major disease-causing genes, and each of these gene mutations presents in more than 20% of all BBS patients. Genotype-phenotype correlations have not been observed in BBS, and there can be phenotypic overlap between BBS and other ciliopathies. In Korea, no molecular, genetically confirmed case of BBS has been reported to date. Herein, we describe the case of the first Korean siblings with BBS resulting from 2 BBS10 gene mutations who showed typical clinical phenotypes, including retinal dystrophy, obesity, intellectual disability, cystic tubular disease, and postaxial polydactyly.

Morphologic Characteristics of the Outer Retina in Cone Dystrophy on Spectral-domain Optical Coherence Tomography

PURPOSE: To investigate the morphologic changes in the outer retina of patients with cone dystrophy, using spectral-domain optical coherence tomography (SD-OCT). METHODS: The medical records of 15 cone dystrophy patients examined from January 2007 to January 2012 were reviewed retrospectively. All patients underwent ophthalmic evaluation including best-corrected visual acuity (BCVA), color vision testing, fundus examination, full-field standard electroretinography (ERG), multifocal (mf) ERG, and SD-OCT. Qualitative and quantitative SD-OCT data and ERG responses were analyzed and compared among the patient categories and the normal control group. RESULTS: There were 4 major categories of SD-OCT findings, based on the status of the ellipsoid portion of the photoreceptor inner segment (ISe), outer segment (OS) contact cylinder, and retinal pigment epithelium (RPE) layer. Category 0 showed no structural abnormalities. Category 1 showed foveal ISe loss and obscurity of the border between the ISe band and the external limiting membrane (ELM). Category 2 showed foveal thinning and focal foveal ISe disruption with an intact ELM. Category 3 showed foveal thickening and perifoveal disruption of the ISe layer. Category 1 to 3 showed OS contact cylinder layer absence and RPE thickening. The patients in category 0 tended to be younger (mean, 10.0 years) than those in categories 1 to 3 (mean, 17.6 years), although this difference was not statistically significant. Category 1 to 3 patients exhibited statistically significant thinning of the central retina and outer nuclear layer and thickening of the RPE layer relative to the category 0 and normal control group. There was a significant correlation between the central foveal thickness and BCVA in the patients with cone dystrophy. ERG and mfERG responses did not differ significantly among the different cone dystrophy categories. CONCLUSIONS: The morphologic features of cone dystrophy as revealed by SD-OCT, could be categorized as either normal or 1 of 3 different types of outer retinal changes. The presence of normal retinal structures in young cone dystrophy patients with functional impairment (category 0) indicates that electrophysiologic studies are superior to current imaging modalities for the early diagnosis of cone dystrophy. The characteristic SD-OCT findings in cone dystrophy patients may aid in differential diagnosis and be useful for future research on the pathology of cone dystrophy.

A Case of Joubert Syndrome Associated with Nephrocalcinosis and Agenesis of Cerebellar Vermis

There are several diseases characterized by neurologic abnormalities and renal disease. Joubert syndrome is one of them. Joubert syndrome is a relatively rare autosomal recessive syndrome. The most significant and constant neurologic finding is hypoplasia of the cerebellar vermis. Joubert syndrome is associated with hypotonia, retinal dystrophy, abnormal eye movement, delayed development, abnormal respiratory pattern (neonatal episodic tachypnea or apnea) and nephronophthisis. We report a boy with Joubert syndrome associated with nephrocalcinosis and agenesis of the cerebellar vermis. This patient had also abnormal eye movement, hypotonia, abnormal respiratory pattern, delayed development and chronic renal failure.

A Case of Joubert Syndrome

Joubert syndrome is frequently associated with developmental delay and mental retardation, neonatal tachypnea and apnea, abnormal eye movements, and ataxia. It is inherited by an autosomal recessive trait. The most significant and constant neuropathological finding is partial or total agenesis of cerebellar vermis. Absence of the vermis results in a triangular -shaped mid-fourth ventricle and a "bat-wing"shaped fourth ventricle superiorly. The superior cerebellar peduncles are nearly horizontal. Retinal dystrophy, ocular motility disorders, and polydactyly may also occur. Symptoms may occur during the neonatal period and prognosis is grave. We report a typical case of Joubert syndrome in a 5 months-old female with developmental delay, tachypnea and intermittent apnea, abnormal eye movements, axial ataxia, and agenesis of the cerebellar vermis on brain MRI and SPECT and a brief review of related literature are also contained.

Clinical Study of Symptoms and Various Anomalies of Patients with Joubert Syndrome

PURPOSE: Joubert syndrome is known to be an autosomal recessive disorder characterized by cerebellar vermian dysgenesis with many symptoms and variety of other malformations. We studied the relevant symptoms and various malformations of seven patients diagnosed as Joubert syndrome at our institution. METHODS: Seven children with cerebellar vermian dysgenesis consistent with Joubert syndrome were included in our study. Each child was diagnosed at the Seoul National University Children's Hospital from Feb. 1991 to Feb. 1995. We studied the frequency of each symptom of Joubert syndrome and the associated malformations of the selected cases. RESULTS: All seven patients had no family members affected. Also their parental consanguinity were not found. Sex ratio was 1.3 : 1 (4 males and 3 females) showing no significant sex difference. Ages at diagnosis were less than one year old. Six patients in our study had developmental delay, which was the most frequent symptom. Four patients had ataxia; four patients had hypotonia; three patients had abnormal ocular movements such as nystagmus or saccadic palsy; only one patient had episodic tachypnea in neonatal period; and in one case there were tongue protrusion and seizure, respectively. In two cases there were occipital meningoceles, agenesis of corpus callosum, and cleft palates, respectively. In one case there were cystic renal disorder, neuronal heterotopia, absence of septum pellucidum, and polydactyly, respectively. None had retinal dystrophy or chorioretinal coloboma. CONCLUSIONS: The cardinal symptoms of Joubert syndrome are unexplainable episodic tachypnea alternating with apnea during neonatal period, abnormal ocular movement such as nystagmus or saccadic palsy, ataxia, hypotonia, and developmental delay. The presence of such symptoms should alert the clinician to apply appropriate test such as neuroradiologic study including brain MRI etc. Some of the inconstantly associated features of Joubert syndrome include congenital retinal dystrophy, chorioretinal coloboma, and cystic kidney disease. The patients should be examined routinely with electroretinogram, fundoscopy, and kidney ultrasonogram for early detection or exclusion of the associated anomalies. We stress the importance of genetic counselling for the families of Joubert syndrome as well as that of the prompt supportive therapy for the patient.

Congenital Ocular Motor Apraxia without Head Thrusts: A Case of Joubert Syndrome

Joubert syndrome is the very rare autosomal recessive disorder which is including agenesis of cerebellar vermis, respiratory discomfort, ocular motor apraxia, hereditary retinal dystrophy, ataxia and developmental retardation. To diagnose, the findings of electroretinography and visual evoked potential study can be useful and hypoplasia of cerebellar vermis in brain MRI can make certain diagnosis. We found ocular motor apraxia without head thrusts in 4-month little baby can't even control his head and neck, and then his electroretinography and visual evoked potential study was normal and there was agenesis of cerebellar vermis by MRI finding. So he was diagnosed as Joubert syndrome with ocular motor apraxia. Agenesis of cerebellar vermis is considered to be one of the causes of oculomotor apraxia, and the clinical presentation varies with the age and motor development of the child. So, we describe this case with a brief review of the literatures related to this disease.