Exome sequencing identifies novel genes underlying primary congenital glaucoma in the National Birth Defects Prevention Study.

BACKGROUND: Primary congenital glaucoma (PCG) affects approximately 1 in 10,000 live born infants in the United States (U.S.). PCG has a autosomal recessive inheritance pattern, and variable expressivity and reduced penetrance have been reported. Likely causal variants in the most commonly mutated gene, CYP1B1, are less prevalent in the U.S., suggesting that alternative genes may contribute to the condition. This study utilized exome sequencing to investigate the genetic architecture of PCG in the U.S. and to identify novel genes and variants. METHODS: We studied 37 family trios where infants had PCG and were part of the National Birth Defects Prevention Study (births 1997-2011), a U.S. multicenter study of birth defects. Samples underwent exome sequencing and sequence reads were aligned to the human reference sample (NCBI build 37/hg19). Variant filtration was conducted under de novo and Mendelian inheritance models using GEMINI. RESULTS: Among candidate variants, CYP1B1 was most represented (five trios, 13.5%). Twelve probands (32%) had potentially pathogenic variants in other genes not previously linked to PCG but important in eye development and/or to underlie Mendelian conditions with potential phenotypic overlap (e.g., CRYBB2, RXRA, GLI2). CONCLUSION: Variation in the genes identified in this population-based study may help to further explain the genetics of PCG.

Assessment of tear film parameters in females with refractive errors using a single device: An observational study.

This observational study aimed to evaluate the use of a single portable device to assess the non-invasive tear break-up time (NITBUT), tear meniscus height (TMH), and lipid layer patterns (LLP) in young females with refractive errors (REs). The study was conducted at the College of Applied Medical Science (Female campus), Riyadh, Saudi Arabia between January 5, 2021 to May 15, 2021. Forty young females, with mean age of 23.0± 4.3 years with REs (-2.53 ± 2.05 D) and 40 females, mean age 23.8± 4.5 years with healthy eyes were recruited. The tests were administered in the following order: Ocular Surface Disease Index (OSDI), followed by NITBUT, TMH, and LLP. Significant differences (via Mann-Whitney U test) were noted in the median ocular surface disease index (OSDI; p˂0.001), NITBUT (p=0.035), TMH (p=0.009), and LLP (p˂0.001) scores between the study and control groups. Females with REs have significantly lower lipid layer, TMH, and NITBUT scores than those with healthy eyes.

Findings of ocular examinations in healthy full-term newborns / Achados de exame ocular realizado em recém-nascidos a termo saudáveis

ABSTRACT Purpose: To assess the anterior and posterior segments of full-term neonates over a 1.5-year period. Methods: The findings of full-term neonates who underwent ophthalmological examinations between June 2019 and December 2020 were analyzed, and the results were retrospectively recorded. Results: The study comprised 2972 neonates with a mean birth week of 38.7 ± 1.2 weeks and a mean birth weight of 3235 ± 464 g. The neonates were examined on an average of 49.3 ± 18.9 postnatal days. Of the examined neonates, 185 (6.2%) showed abnormal ophthalmological findings, the most prevalent of which were retinal hemorrhage in 2.3% (n=68) and white changes in the peripheral retina in 1.9% (n=55) of the neonates. Cases of optic disc pathologies (n=20), choroidal nevus (n=10), iris-choroidal coloboma (n=5), subconjunctival hemorrhage (n=6), non-specific retinal pigmentary change (n=4), congenital cataract (n=3), posterior synechia (n=3), iris nevus (n=3), corneal opacity (n=1), choroidal coloboma (n=1), iris coloboma (n=1), buphthalmos (n=1), anophthalmos (n=1), microphthalmia (n=1), lid hemangioma (n=1), and vitreous hemorrhage (n=1) collectively accounted for approximately 2% of all neonates. Pathologies that could potentially impair vision, which were detected by ophthalmological examination, accounted for 1.2% of all neonates (n=37). Conclusion: The most prevalent finding of the ophthalmological examinations of neonates in the present study was retinal hemorrhage. Ophthalmological examinations of neonates can help in identifying diseases that may affect their vision and are curable or may lead to amblyopia in the long term.

RESUMO Objetivo: Avaliar os segmentos anterior e posterior em recém-nascidos a termo durante um período de 1,5 anos. Métodos: Foram analisados recém-nascidos a termo que tiveram os olhos examinados entre junho de 2019 e dezembro de 2020, e os resultados foram registrados retrospectivamente. Resultados: O estudo foi composto por 2.972 recém-nascidos com média de uma semana de nascimento de 38,7 ± 1,2 semanas e um peso médio ao nascer de 3235 ± 464 g. Os recém-nascidos foram examinados em média pós-natal de 49,3 ± 18,9 dias. Dos recém-nascidos, 185 (6,2%) apresentaram resultados oculares anormais. Os achados oculares anormais mais prevalentes foram hemorragia da retina em 2,3% (n=68) e alterações brancas na retina periférica em 1,9% (n=55) dos recém-nascidos. Casos de patologias de disco óptico (n=20), nevo de coroide (n=10), coloboma iris-coroide (n=5), hemorragia subconjuntival (n=6), alteração pigmentar da retina não específica (n=4), catarata congênita (n=3), Sinequia posterior (n=3), nevo da íris (n=3), opacidade da córnea (n=1), coloboma de coroide (n=1), coloboma de íris (n=1), buftalmos (n=1), anoftalmia (n=1), microftalmia (n=1), hemangioma de pálpebra (n=1) e hemorragia vítrea (n=1) contabilizaram coletivamente cerca de 2% dos recém-nascidos. As patologias que potencialmente prejudicam a visão, detectadas por exame ocular, representaram 1,2% dos recém-nascidos (n=37). Conclusão: O achado mais prevalente de exames oculares de recém-nascidos neste estudo foi hemorragia da retina. Exames oftalmológicos em recém-nascidos podem ser úteis na identificação de doenças que podem impactar a visão deles, podendo ser curáveis ou levar à ambliopia no longo prazo.

Eye Abnormalities in Children with Fetal Alcohol Spectrum Disorders: A Systematic Review.

PURPOSE: Although eye abnormalities are reported in fetal alcohol spectrum disorders (FASD), no systematic review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines has been undertaken. Our aim was to document the range and prevalence of eye abnormalities reported in children with prenatal alcohol exposure (PAE) and/or FASD. METHODS: Searches of electronic databases and manual searches. Eligible articles were observational studies in children with PAE and/or FASD; peer reviewed journal articles in the English language; and studies reporting quantitative or frequency data on functional/structural eye abnormalities. Pooled prevalence, odds ratio, and mean differences were calculated. RESULTS: Of the 1,068 retrieved articles 36 were eligible, including articles on children with diagnosed fetal alcohol syndrome/FASD (N = 31); PAE (N = 3); and FASD or PAE without FASD (N = 2). Structural and functional eye abnormalities were identified, the most prevalent being short palpebral fissure length (66.1%), visual impairment (55.5%), epicanthus (53.5%), subnormal stereoacuity (53.0%), abnormal retinal tortuosity (50.5%), impaired fixation ability (33.3%), telecanthus (31.7%), optic nerve hypoplasia (30.2%), and small optic discs (27.0%). Compared to non-exposed controls, strabismus, subnormal vision, ptosis, short palpebral fissure length, microphthalmos, smaller optic disc area, and retinal vessel tortuosity were more prevalent in children with FASD. CONCLUSIONS: Examination of eyes and vision should be considered in children with PAE and suspected or diagnosed FASD to enable early identification and optimal management. This first comprehensive, systematic literature review demonstrates the variety and frequency of eye abnormalities reported in PAE/FASD.

Mejoramiento estético en paciente con tisis bulbi

Introducción: El ojo es un órgano esencial para la relación con el entorno y para el desarrollo del ser humano, es fundamental poseer una adecuada salud visual. Objetivo: Describir la confección de una prótesis ocular para el mejoramiento estético en un paciente con tisis bulbi en ojo derecho. Caso clínico: Paciente masculino, de raza blanca, de 59 años de edad que llega a la consulta de Prótesis del Policlínico Universitario Julio Antonio Mella de la provincia Camagüey remitido de Servicios de Oftalmología con diagnóstico de tisis bulbi del ojo derecho. Al interrogatorio plantea que cuando niño, jugando con su hermano recibió un golpe en el ojo, por el cual fue tratado en el servicio de Oftalmología del Hospital Pediátrico Eduardo Agramonte Piña de la ciudad de Camagüey. Tuvo una pérdida visual progresiva que finalizó en ceguera y cambio de coloración del ojo. Refiere que nunca ha tenido dolor, pero le preocupa su estética. Conclusiones: El tratamiento protésico de la tisis del globo ocular, es una situación desafiante para el equipo rehabilitador, dada las características de este defecto. Con la utilización de este tipo de prótesis oculares en la rehabilitación del paciente, se logró mejorar su estética, lo que condujo a la recuperación física, psíquica y social.

Introduction: The eye is an essential organ for the relationship with the environment, and for the development of the human being it is essential to have adequate visual health. Objective: To describe the preparation of an ocular prosthesis for aesthetic improvement in a patient with phthisis bulbi in the right eye. Clinical case: A 59-year-old white male patient who arrived at the prosthesis clinic of the Julio Antonio Mella University Polyclinic in the province of Camagüey, referred from Ophthalmology Services with a diagnosis of phthisis bulbi of the right eye. Upon interrogation, he states that when he was a child, playing with his brother, he received a blow to the eye, for which he was treated at the ophthalmology service of the Eduardo Agramonte Piña Pediatric Hospital in the city of Camagüey. He had progressive visual loss that ended in blindness and eye color change. He says that he has never had pain, but he is concerned about his aesthetics. Conclusions: The prosthetic treatment of ocular globe phthisis is a challenging situation for the rehabilitation team, given the characteristics of this ocular defect. With the use of this type of ocular prosthesis in the patient's rehabilitation, it was possible to improve their aesthetics, which led to physical, mental and social recovery.

Bilateral congenital dacryocystocele complicated with acute dacryocystitis / Dacriocistocele congênita bilateral complicada com dacriocistite aguda

ABSTRACT Congenital dacryocystocele is an uncommon entity that results from a malformation of the nasolacrimal system, occurring predominantly in neonatal females. It may resolve spontaneously but can be associated with potentially serious complications as acute dacryocystitis, requiring referral to an ophthalmologist. Bilateral cases of congenital dacryocystocele are rarely reported. We present a case of acute dacryocystitis occurring in a female newborn with bilateral congenital dacryocystocele who presented with bilateral epiphora and a mass in the right medial canthus since birth. Computed tomography revealed a bilateral soft tissue lesion in the medial canthus of the ocular globe. Dacryocystocele progressed to secondary infection on the right and patient developed acute dacryocistitis. She was admitted to the hospital for intravenous antibiotic therapy followed by the nasolacrimal system probing. This case report is also important to address the management of congenital dacryocystocele, and the decision to carry out the most suitable treatment, considering the diverse therapeutic options.

RESUMO A dacriocistocele congênita é uma entidade incomum, que resulta de uma malformação do sistema nasolacrimal, ocorrendo predominantemente em recém-nascidos do sexo feminino. Pode se resolver espontaneamente, mas também pode estar associada a complicações potencialmente graves, como dacriocistite aguda, necessitando de encaminhamento a um oftalmologista. Raramente são relatados casos bilaterais de dacriocistocele congênita. Relatamos um caso de dacriocistite aguda acometendo um recém-nascido do sexo feminino. Ele apresentava dacriocistocele congênita bilateral, que apresentava epífora bilateral e uma massa no canto medial direito desde o nascimento. A tomografia computadorizada revelou lesão bilateral de partes moles no canto medial do globo. A dacriocistocele apresentou infecção secundária à direita, e a paciente desenvolveu dacriocistite aguda. Ela foi internada no hospital para antibioticoterapia intravenosa seguida de sondagem do sistema nasolacrimal. Este relato de caso também é importante para abordar o manejo da dacriocistocele congênita e a decisão de realizar o tratamento mais adequado, considerando as diversas opções terapêuticas.

Disruption of fetal eye development caused by insulin-induced maternal hypoglycemia in rats.

We previously revealed that insulin-induced severe and long-lasting maternal hypoglycemia in rats caused anophthalmia and microphthalmia in fetuses; however, it remained unclear whether hypoglycemia-induced eye anomalies were developmental retardation or disruption, and when and how they developed. Hence, we induced hypoglycemia in pregnant Sprague-Dawley rats by injecting insulin from Days 6 to 11 of pregnancy and performed periodical histopathological examination of fetal eyes from embryonic days (E)10 to 20. On E10, optic vesicle had developed normally both in the control and insulin-treated group; however, on E11, optic cup (OC) had developed in the control group but not in the insulin-treated group. On E12, neural retina (NR), retinal pigmented epithelium (RPE), lens, and presumptive cornea had been observed in the control group. In contrast, lens pit and OC with remaining space between RPE and NR had developed in the insulin-treated group. From E13 to E15, developmental disruption characterized by defects, hypoplasia, and degeneration in the retina, lens, and cornea was observed in the insulin-treated group, resulting in anophthalmia or microphthalmia on E20. Moreover, the expression of MITF and chx10, which are essential for early eye development by expressing in the presumptive retina and lens and regulating each other's expression level, was ectopic and suppressed on E11. In conclusion, insulin-induced maternal hypoglycemia caused developmental disruption, but not simple developmental retardation of fetal eyes, and its trigger might be a failure of presumptive retina and lens to interact on E11.

Exome sequencing identifies genetic variants in anophthalmia and microphthalmia.

Anophthalmia and microphthalmia (A/M) are rare birth defects affecting up to 2 per 10,000 live births. These conditions are manifested by the absence of an eye or reduced eye volumes within the orbit leading to vision loss. Although clinical case series suggest a strong genetic component in A/M, few systematic investigations have been conducted on potential genetic contributions owing to low population prevalence. To overcome this challenge, we utilized DNA samples and data collected as part of the National Birth Defects Prevention Study (NBDPS). The NBDPS employed multi-center ascertainment of infants affected by A/M. We performed exome sequencing on 67 family trios and identified numerous genes affected by rare deleterious nonsense and missense variants in this cohort, including de novo variants. We identified 9 nonsense changes and 86 missense variants that are absent from the reference human population (Genome Aggregation Database), and we suggest that these are high priority candidate genes for A/M. We also performed literature curation, single cell transcriptome comparisons, and molecular pathway analysis on the candidate genes and performed protein structure modeling to determine the potential pathogenic variant consequences on PAX6 in this disease.

Comportamiento de los pacientes con distrofia corneal endotelial de Fuchs en la provincia Camagüey

Introducción: La distrofia corneal endotelial de Fuchs se trata de un trastorno degenerativo específico, bilateral y progresivo del endotelio corneal, es la más frecuente pero no siempre es diagnosticada en sus etapas iniciales en las consultas de oftalmología general. Objetivo: Describir el comportamiento clínico de pacientes con distrofia corneal endotelial de Fuchs en la provincia Camagüey. Métodos: Se realizó un estudio observacional, descriptivo, transversal en el Centro Oftalmológico del Hospital Universitario Manuel Ascunce Domenech en la provincia Camagüey desde noviembre 2019 hasta junio 2021. El universo de estudio estuvo constituido por todos los pacientes que asistieron durante el periodo de estudio y la muestra la conformaron 19 pacientes (38 ojos) quienes cumplieron con los criterios de inclusión y exclusión. Las variables estudiadas fueron edad, sexo, color de la piel, agudeza visual con corrección, asociación con glaucoma, paquimetría, biomicroscopía del segmento anterior, microscopía endotelial, microscopía confocal, estadio de la enfermedad y tipo de tratamiento aplicado. Resultados: Predominaron los pacientes entre 40 y 59 años de edad, el sexo femenino y color blanco de la piel. Sobresalió la visión útil, los valores de paquimetría altos y asociados al glaucoma. Se constató la presencia de guttas, edema corneal, bajo conteo celular con polimorfismo y polimegatismo. El estadio 2 estuvo en 47,4 % y el tratamiento médico se aplicó en el 97,4 %. Conclusiones: La distrofia aparece con más frecuencia después de los 40 años de edad, en sexo femenino y color blanco de piel. Predominó la visión útil, valores altos de paquimetrías y asociación con glaucoma. En la biomicroscopía del segmento anterior predominaron las guttas y el edema estromal y la microscopía endotelial y confocal se caracterizaron en su mayoría por el bajo conteo celular, las guttas, polimorfismo y polimegatismo. Prevaleció el estadio 2 y el tratamiento médico.

Introduction: Fuchs endothelial corneal dystrophy is a specific, bilateral and progressive degenerative disorder of the corneal endothelium, it is the most frequent but it is not always diagnosed in its initial stages in general ophthalmology consultations. Objective: To describe the clinical behavior of patients with Fuchs endothelial corneal dystrophy in Camagüey province. Methods: A cross-sectional descriptive observational study was carried out at the Ophthalmological Center of the Manuel Ascunce Domenech University Hospital in Camagüey in the period from November 2019 to June 2021. The study universe consisted of all the patients who attended during the study period and the sample was made up of 19 patients (38 eyes) who met the inclusion and exclusion criteria. The variables studied were age, sex, skin color, corrected visual acuity, association with glaucoma, pachymetry, anterior segment biomicroscopy, endothelial microscopy, confocal microscopy, disease stage, and type of treatment applied. Results: Patients between 40 and 59 years of age, female sex, and white skin color predominated. Useful vision stood out, high pachymetry values and associated with glaucoma, the presence of guttas, corneal edema, low cell count with polymorphism, and polymegatism was confirmed. Stage 2 was 47.4% and medical treatment was applied in 97.4%. Conclusions: Dystrophy appears more frequently after 40 years of age, in females and white skin persons. Useful vision, high pachymetry values, and association with glaucoma prevailed. In the biomicroscopy of the anterior segment, guttas and stromal edema predominated, and endothelial and confocal microscopy were mostly characterized by low cell count, guttas, polymorphism, and polymegatism. Stage 2 and medical treatment prevailed.

Caracterización de los pacientes con defectos oculares atendidos en el Policlínico Universitario Julio Antonio Mella

Introducción: La prótesis bucomaxilofacial constituye la rehabilitación morfofuncional por medios artificiales de las estructuras intrabucales y peribucales en los defectos oculares, orbitales, nasales, auriculares, maxilares, mandibulares, craneales y complejos; con la conservación de modo armónico de las estructuras remanentes ya sean duros o blandos. Objetivo: Caracterizar los pacientes rehabilitados por defectos oculares en el Policlínico Universitario Julio Antonio Mella. Métodos: Se realizó un estudio observacional, descriptivo y transversal desde enero de 2015 a febrero de 2022 en pacientes rehabilitados por defectos oculares en el departamento de Prótesis Estomatológica del Policlínico Universitario Julio Antonio Mella de la ciudad de Camagüey. Se estudiaron 53 pacientes que acudieron en el período de la investigación remitidos del Hospital Universitario Manuel Ascunce Domenech y del Hospital Pediátrico Provincial Docente Eduardo Agramante Piña de la provincia Camagüey. Resultados: Con relación a los pacientes con rehabilitados según edad, sexo y factores etiológicos prevaleció el grupo 35 a 59 años, así como el sexo masculino y el traumatismo ocular. Se constató que la experiencia protésica satisfactoria primó en los periodos evaluados y con respecto a los pacientes rehabilitados según los factores relacionados con la estética, se comprobó que los valores más favorables fueron para el color de la esclera y la apertura palpebral. Conclusiones: Predominó el sexo masculino junto con el grupo de edad de 35 59 años. La causa más frecuente de pérdida ocular fue la traumática. Hubo un alto índice de experiencia satisfactoria con el uso de las prótesis y los factores que determinaron la estética fueron favorables.

Introduction: The bucomaxilofacial prosthesis constitutes the morpho-functional rehabilitation for artificial means of the intraoral and peribucales structures in the ocular defects, orbital, nasal, aural, maxillary, mandibular, cranial and complex; with the harmonic conservation of mode of the remanent structures either be hard or soft. Objetive: To characterize the patients rehabilitated for ocular defects at the Julio Antonio Mella University Polyclinic. Methods: An observational, descriptive and transversal study was carried out from January, 2015 to February, 2022 in patients rehabilitated by ocular defects in the department Dentistry Prosthesis of the Julio Antonio Mella University Polyclinic of the city of Camagüey. 53 patients constituted the universe that attended in the period of the investigation remitted of the Manuel Ascunce Domenech University Hospital and from the Eduardo Agramontes Piña Provincial Pediatric Hospital in the province Camagüey. Results: With respect to the rehabilitated patients according to age, sex and etiologic factors prevailed the group 35 to 59 years, as well as the masculine sex and the ocular traumatism. It was verified that the prosthetic satisfactory experience had priority in the evaluated periods and regarding the patients rehabilitated according to the factors related with esthetics, it was verified that the most favorable values were for the color of the esclera and the palpebral opening. Conclusions: The masculine patients predominated along with the age rank of 35-59 years. The most frequent cause of ocular loose was the traumatic one. There was a tall index of satisfactory experience with the use of the prosthesis and the factors that determined the esthetics were favorable.

Clinical and neurodevelopmental outcomes based on brain imaging studies in a Colombian cohort of children with probable antenatal Zika virus exposure.

BACKGROUND: Our aim was to describe the neuroimaging and clinical evaluations of children with antenatal Zika-virus (ZIKV) exposure. METHODS: The Colombian National Institute of Health performed serial clinical evaluations of children with probable antenatal ZIKV exposure (i.e., born to ZIKV symptomatic mothers or born with birth defects compatible with ZIKV infection, regardless of laboratory results) over 2 years that included head circumference (HC), eye examination, and neurodevelopmental assessments. Clinical neuroimaging studies (head computed tomography and/or brain magnetic resonance imaging) were analyzed for abnormalities, two-dimensional measurements were made of the right and left frontal and occipital cortical thickness. Two abnormal patterns were defined: Pattern 1 (sum of four areas of cortex <6 cm) and Pattern 2 (sum of four areas of cortex ≥6 cm and < 10 cm). RESULTS: Thirty-one children had a neuroimaging study; in 24, cortical thickness was measured. The median age at the first visit was 8 (range: 6-9) months and 22 (range: 19-42) months at the last evaluation. In the 24 cases with cortical measurements, three were normal, 12 were in Pattern 1, and nine were in Pattern 2. Children within Pattern 1 had lower mean HC at birth and in follow-up (both p < .05) and a higher frequency of structural eye abnormalities (p < .01). A trend towards poorer neuromotor development was seen in Pattern 1, although not statistically significant (p = .06). CONCLUSION: Brain imaging classification based on cortical measurements correlate with ophthalmologic abnormalities and HC. Cortical thickness may be a marker for clinical outcomes in children with congenital ZIKV infection.

Síndrome de Joubert: incidencia y descripción clinicorradiológica de una serie genotipada de siete casos / Joubert syndrome: incidence and clinicoradiological description of a genotyped series of seven cases

Introducción: El síndrome de Joubert se produce por una alteración de las proteínas ciliares esenciales para la estructura y la función de neuronas y órganos como los riñones, el hígado, la retina y el oído. Se conocen unas 34 mutaciones en la actualidad. Objetivo: Calcular la incidencia/prevalencia y describir el fenotipo/genotipo y las alteraciones clinicorradiológicas de esta ciliopatía en nuestra área de salud. Pacientes y métodos: Revisamos las historias clínicas con diagnóstico de síndrome de Joubert en los últimos 10 años para recoger el fenotipo, las características radiológicas y las manifestaciones extraneurológicas en relación con la alteración genética detectada. Resultados: Se incluyeron siete casos, de los cuales cinco eran varones (6-17 años). Presentaban seis mutaciones diferentes. Fue constante la hipotonía, los dedos finos/largos y el retraso en el desarrollo psicomotor. Presentaban rasgos dismórficos, retraso mental, apraxia ocular y nistagmo indistintamente, 3/7; apnea/hiperpnea neonatal, 2/7; hipoplasia de vermis, 7/7; síndrome del molar, 6/7; elongación-adelgazamiento de los pedúnculos cerebelosos, 2/7; estrechez en la unión pontomesencefálica, 6/7, y fastigio del IV ventrículo alto, 4/7. Entre las complicaciones somáticas había: retinopatía, 2/7; coloboma retiniano, 1/7; fibrosis hepática, 1/7; nefronoptisis, 1/7, y quiste renal 1/7. Conclusiones: La incidencia del síndrome de Joubert fue de al menos 1/20.000 recién nacidos/año. Las alteraciones radiológicas pontomesencefálicas y pedunculares fueron constantes. La hipotonía, el retraso psicomotor y los dedos finos/largos afectaron a todos los casos.(AU)

Introduction: Joubert syndrome is produced by an alteration of the ciliary proteins essential for the structure and function of neurons and organs such as the kidneys, liver, sight, and hearing. Some 34 mutations are currently known. Objective: Calculate the incidence / prevalence, describe the phenotype / genotype and radiological alterations of this ciliopathy in our health area. Patients and methods: We reviewed the medical records with a diagnosis of Joubert Syndrome in the last 10 years to collect phenotype, radiological characteristics, and extra-neurological manifestations in relation to the genetic alteration detected. Results: 7 cases were included: 5 children (6 -17 years). They had 6 different mutations. Hypotonia, thin / long fingers and delayed psychomotor development were constant. They presented dysmorphic features, mental retardation, ocular apraxia, and nystagmus indistinctly in 3/7; Neonatal apnea/hyperpnea 2/7; hypoplasia of vermis 7/7; Molar syndrome was evident in 6/7 and in 2/7 there was elongation-thinning of cerebellar peduncles. Pontomesencephalic junction tightness 6/7; fastigium of the IV ventricle high in 4/7. Among the somatic complications, retinopathy 2/7, retinal coloboma 1/7, liver fibrosis 1/7, nephronoptysis 1/7 and renal cyst 1/7. Conclusions: The incidence of Joubert syndrome was at least 1 / 20,000 newborns / year. The pontomesencephalic and peduncular radiological alterations were constant. Hypotonia, psychomotor retardation, and thin / long fingers affected all cases.(AU)

Minor dysmorphic features in a patient with papillorenal syndrome: A Case Report.

Papillorenal syndrome, also known as renal coloboma syndrome, is characterised by congenital optic disc anomalies and renal abnormalities. Mutations in the PAX2 gene, which plays a critical role in embryogenesis, cause this syndrome. Other related anomalies are less commonly observed. To our knowledge, this is the first case reported in the literature in which Papillorenal syndrome accompanied various dysmorphic features.

Biallelic deletion in a minimal CAPN15 intron in siblings with a recognizable syndrome of congenital malformations and developmental delay.

Calpainopathies constitute a heterogeneous group of disorders resulting from deficiencies in calpains, calcium-specific proteases that modulate substrates by limited proteolysis. Clinical manifestations depend on tissue-specific expression of the defective calpain and substrate specificity. CAPN15, encoding the Drosophila small optic lobes (sol) homolog, was recently found to cause various eye defects in individuals carrying bi-allelic missense variants. Here we report on two siblings with manifestations reminiscent of Johanson-Blizzard syndrome including failure to thrive, microcephaly, global developmental delay, dysmorphic features, endocrine abnormalities and congenital malformations, in addition to eye abnormalities. Exome sequencing identified a homozygous 47 base-pair deletion in a minimal intron of CAPN15, including the splice donor site. Sequencing of cDNA revealed single exon skipping, resulting in an out-of-frame deletion with a predicted premature termination codon. These findings expand the phenotypic spectrum associated with CAPN15 variants, and suggest that complete loss-of-function is associated with a recognizable syndrome of congenital malformations and developmental delay, overlapping Johanson-Blizzard syndrome and the recently observed brain defects in Capn15 knockout (KO) mice. Moreover, the data highlight the unique opportunity for indel detection in minimal introns.

Ocular manifestations in classic homocystinuria.

BACKGROUND: Classic homocystinuria (HCU), or cystathionine beta-synthase (CBS) deficiency, is a rare inborn error of methionine metabolism. Main clinical features may include skeletal and vascular manifestations, developmental delay, intellectual disability and eye disorders. MATERIAL AND METHODS: This is an observational and retrospective study aiming at describing eye abnormalities presented by a cohort of late-diagnosed HCU patients. Data regarding ophthalmological evaluation included visual acuity, refraction, biomicroscopy, Perkins tonometry, fundus examination, retinography, biometry, ocular ultrasound, optical coherence tomography, anterior segment photography and topography. RESULTS: Ten patients with HCU (20 eyes) were included. The most frequent findings were ectopia lentis(n = 20) and myopia (n = 9). Biometry, ultrasound, OCT and topography findings were available for four patients. One patient had keratoconus; one had abnormal retinal pigmentation; and two had lens surgery scars with irregular astigmatism. CONCLUSIONS: Eye abnormalities are very frequent in late-diagnosed HCU patients. The presence of ectopia lentis should always raise the diagnostic hypothesis of HCU.

Perfil clínico de pacientes dermatológicos encaminhados para avaliação oftalmológica / Clinical profile of dermatological patients referred to ophthalmological evaluation

RESUMO Objetivo: Analisar o perfil clínico de pacientes em acompanhamento dermatológico encaminhados para avaliação oftalmológica. Métodos: A amostra foi composta de pacientes dermatológicos encaminhados para avaliação oftalmológica, nos anos de 2016 e de 2017. Estudou-se a concomitância de doenças dermatológicas com as afecções oftalmológicas por meio da coleta simultânea do histórico dermatológico (prontuários registrados com dados gerais e diagnóstico) e de dados da consulta oftalmológica após o encaminhamento. Resultados: Foram avaliados pela oftalmologia 224 pacientes, sendo 65% do sexo feminino, 80% caucasianos, com idade variando entre 1 mês e 85 anos. As situações cujo encaminhamento foi mais prevalente foram psoríase, lúpus, vitiligo e rosácea (18,3%, 13,8%, 12,9% e 10,7%, respectivamente). Fototerapia crônica e uso de hidroxicloroquina representaram 35,7% e 22,3% dos pacientes. Casos de neurofibromatose, micose fungoide, líquen plano, neoplasias de pele, atopias, pênfigo e esclerodermia também estiveram presentes. Cegueira legal foi detectada em 6%, e deficiências visuais ligadas a afecções dermatológicas foram verificadas em 16,5% dos casos. As alterações oculares mais prevalentes foram catarata (18,9%), blefarite (15,9%), pterígio (5,3%) e conjuntivite (5,3%). Conclusão: Encontrou-se elevada frequência de alterações oftalmológicas em uma população de pacientes com doenças dermatológicas. Assim, o estudo e a análise de manifestações oculares em pacientes dermatológicos podem auxiliar na detecção precoce e na prevenção de complicações.

ABSTRACT Objective: To analyze the clinical profile of patients under dermatological care and referred to ophthalmological evaluation. Methods: The sample comprised dermatology patients referred to ophthalmological evaluation in 2016 and 2017. The simultaneous occurrence of skin and ophthalmic diseases was studied, by collecting dermatological history (medical records containing general data and diagnosis) and ophthalmic consultation data following referral. Results: A total of 224 patients were assessed, 65% were female, 80% were white, and age varied between one month and 85 years. The conditions more often referred were psoriasis, lupus, vitiligo and rosacea (18.3%, 13.8%, 12.9% and 10.7%, respectively). Chronic phototherapy and use of hydroxychloroquine were observed in 35.7% and 22.3% of patients, respectively. Cases of neurofibromatosis, mycosis fungoides, lichen planus, skin cancer, atopic dermatitis, pemphigus and scleroderma were also reported. Legal blindness was detected in 6% and visual impairment related to skin conditions in 16.5% of patients. The most prevalent ocular changes were cataracts (18.9%), blepharitis (15.9%), pterygium (5.3%) and conjunctivitis (5.3%). Conclusion: A high frequency of ophthalmic changes in a population of dermatological patients was found. In this context, studying and analyzing ocular manifestations in dermatological patients could be useful in early detection and prevention of complications.