Phenotypic characterization of retinitis pigmentosa associated with deafness / Caracterización fenotípica de la retinitis pigmentaria asociada a sordera

Introduction: There are several syndromes that associate retinitis pigmentosa with deafness or hearing loss. The most frequent is Usher syndrome, a genetic disorder of autosomal recessive inheritance, which, in some cases, is accompanied by vestibular dysfunction. However, there are cases of families that despite having retinitis pigmentosa associated with deafness, cannot be classified as Usher or other syndromes due to additional findings. Objective: To reassess the phenotypes of 103 families previously diagnosed as possible Usher syndrome and/or retinitis pigmentosa associated with deafness. Materials and methods: We conducted a descriptive and retrospective study by reviewing the medical records of 103 families with a probable clinical diagnosis of Usher syndrome and/or retinitis pigmentosa associated with deafness. Families whose clinical diagnosis did not correspond to the typical Usher syndrome were selected and evaluated ophthalmologically and audiologically. Demographic and clinical variables were analyzed. Results: We selected and then reevaluated 14 families and 55 individuals as they did not correspond to a clinical diagnosis of Usher syndrome; 13.6% of the families initially considered to have typical Usher syndrome were later diagnosed with retinitis pigmentosa associated with deafness, another ocular symptom associated with hearing loss, retinitis pigmentosa, or isolated hearing loss in the same family. Conclusions: Family studies are essential in cases where the symptoms do not match the typical Usher' syndrome. In the cases of retinitis pigmentosa associated with deafness, a correct clinical diagnosis allows for focusing on the molecular analyses to establish a differential diagnosis. The need for nomenclature guidelines on these atypical findings is relevant to aid physicians and researchers in the best approach to these cases.

Introducción. El síndrome de Usher es una alteración genética caracterizada por la asociación de retinitis pigmentaria y sordera. Sin embargo, hay casos con familias en las cuales, a pesar de presentarse dicha asociación, no se puede diagnosticar un síndrome de Usher ni ninguno otro. Objetivo. Reevaluar fenotípicamente a 103 familias con diagnóstico previo de posible síndrome de Usher o retinitis pigmentaria asociada con sordera. Materiales y métodos. Se revisaron las historias clínicas de 103 familias con un posible diagnóstico clínico de síndrome de Usher o retinitis pigmentaria asociada con sordera. Se seleccionaron las familias cuyo diagnóstico clínico no correspondía a un síndrome de Usher típico. Los afectados fueron valorados oftalmológica y audiológicamente. Se analizaron variables demográficas y clínicas. Resultados. Se reevaluaron 14 familias cuyo diagnóstico clínico no correspondía al de síndrome de Usher. De las familias con diagnóstico inicial de síndrome de Usher típico, el 13,6 % recibieron uno posterior de "retinitis pigmentaria asociada con sordera", de "otro síntoma ocular asociado con hipoacusia", o en forma aislada en una misma familia, de "retinitis pigmentaria" o "hipoacusia". Conclusiones. Es fundamental el estudio familiar en los casos en que la clínica no concuerda con el diagnóstico de síndrome de Usher típico. En los pacientes con retinitis pigmentaria asociada con sordera, el diagnóstico clínico acertado permite enfocar los análisis moleculares y, así, establecer un diagnóstico diferencial. Es necesario elaborar guías de nomenclatura en los casos con estos hallazgos atípicos para orientar a médicos e investigadores en cuanto a su correcto manejo.

Caracterización fenotípica de la retinitis pigmentaria asociada a sordera / Phenotypic characterization of retinitis pigmentosa associated with deafness

Introducción. El síndrome de Usher es una alteración genética caracterizada por la asociación de retinitis pigmentaria y sordera. Sin embargo, hay casos con familias en las cuales, a pesar de presentarse dicha asociación, no se puede diagnosticar un síndrome de Usher ni ninguno otro. Objetivo. Reevaluar fenotípicamente a 103 familias con diagnóstico previo de posible síndrome de Usher o retinitis pigmentaria asociada con sordera. Materiales y métodos. Se revisaron las historias clínicas de 103 familias con un posible diagnóstico clínico de síndrome de Usher o retinitis pigmentaria asociada con sordera. Se seleccionaron las familias cuyo diagnóstico clínico no correspondía a un síndrome de Usher típico. Los afectados fueron valorados oftalmológica y audiológicamente. Se analizaron variables demográficas y clínicas. Resultados. Se reevaluaron 14 familias cuyo diagnóstico clínico no correspondía al de síndrome de Usher. De las familias con diagnóstico inicial de síndrome de Usher típico, el 13,6 % recibieron uno posterior de "retinitis pigmentaria asociada con sordera" de "otro síntoma ocular asociado con hipoacusia',' o en forma aislada en una misma familia, de "retinitis pigmentaria" o "hipoacusia'.' Conclusiones. Es fundamental el estudio familiar en los casos en que la clínica no concuerda con el diagnóstico de síndrome de Usher típico. En los pacientes con retinitis pigmentaria asociada con sordera, el diagnóstico clínico acertado permite enfocar los análisis moleculares y, así, establecer un diagnóstico diferencial. Es necesario elaborar guías de nomenclatura en los casos con estos hallazgos atípicos para orientar a médicos e investigadores en cuanto a su correcto manejo.

Introduction: There are several syndromes that associate retinitis pigmentosa with deafness or hearing loss. The most frequent is Usher syndrome, a genetic disorder of autosomal recessive inheritance, which, in some cases, is accompanied by vestibular dysfunction. However, there are cases of families that despite having retinitis pigmentosa associated with deafness, cannot be classified as Usher or other syndromes due to additional findings. Objective: To reassess the phenotypes of 103 families previously diagnosed as possible Usher syndrome and/or retinitis pigmentosa associated with deafness. Materials and methods: We conducted a descriptive and retrospective study by reviewing the medical records of 103 families with a probable clinical diagnosis of Usher syndrome and/or retinitis pigmentosa associated with deafness. Families whose clinical diagnosis did not correspond to the typical Usher syndrome were selected and evaluated ophthalmologically and audiologically. Demographic and clinical variables were analyzed. Results: We selected and then reevaluated 14 families and 55 individuals as they did not correspond to a clinical diagnosis of Usher syndrome; 13.6% of the families initially considered to have typical Usher syndrome were later diagnosed with retinitis pigmentosa associated with deafness, another ocular symptom associated with hearing loss, retinitis pigmentosa, or isolated hearing loss in the same family. Conclusions: Family studies are essential in cases where the symptoms do not match the typical Usher' syndrome. In the cases of retinitis pigmentosa associated with deafness, a correct clinical diagnosis allows for focusing on the molecular analyses to establish a differential diagnosis. The need for nomenclature guidelines on these atypical findings is relevant to aid physicians and researchers in the best approach to these cases.

An update on Fanconi anemia: Clinical, cytogenetic and molecular approaches (Review).

Fanconi anemia is a genetic syndrome clinically characterized by congenital malformations that affect several human systems, leads to progressive bone marrow failure and predisposes an individual to cancer, particularly in the urogenital area as well as the head and neck. It is commonly caused by the biallelic compromise of one of 22 genes involved in the FA/BRCA repair pathway in most cases. The diagnosis is based on clinical suspicion and confirmation using genetic analysis, where the chromosomal breakage test is considered the gold standard. Other diagnostic methods used include western blotting, multiplex ligation-dependent probe amplification and next-generation sequencing. This genetic condition has variable expressiveness, which makes early diagnosis difficult in certain cases. Although early diagnosis does not currently allow for improved cure rates for this condition, it does enable healthcare professionals to perform a specific systematic follow-up and, if indicated, a bone marrow transplantation that improves the mobility and mortality of affected individuals. The present review article is a theoretical revision of the pathophysiology, clinical manifestations and diagnosis methods intended for different specialists and general practitioners to improve the diagnosis of this condition.

CNVs in the 22q11.2 Chromosomal Region Should Be an Early Suspect in Infants with Congenital Cardiac Disease.

BACKGROUND: Congenital heart disease (CHD) is the most common congenital malformation, it is frequently found as an isolated defect, and the etiology is not completely understood. Although most of the cases have multifactorial causes, they can also be secondary to chromosomal abnormalities, monogenic diseases, microduplications or microdeletions, among others. Copy number variations (CNVs) at 22q11.2 are associated with a variety of symptoms including CHD, thymic aplasia, and developmental and behavioral manifestations. We tested CNVs in the 22q11.2 chromosomal region by MLPA in a cohort of Colombian patients with isolated CHD to establish the frequency of these CNVs in the cohort. METHODS: CNVs analysis of 22q11.2 by MLPA were performed in 32 patients with apparently isolate CHD during the neonatal period. Participants were enrolled from different hospitals in Bogotá, and they underwent a clinical assessment by a cardiologist and a clinical geneticist. RESULTS: CNVs in the 22q11.2 chromosomal region were found in 7 patients (21.9%). The typical deletion was found in 6 patients (18.75%) and atypical 1.5 Mb duplication was found in 1 patient (3.1%). CONCLUSIONS: CNVs in 22q11.2 is a common finding in patients presenting with isolated congenital cardiac disease, therefore these patients should be tested early despite the absence of other clinical manifestations. MLPA is a very useful molecular method and provides an accurate diagnosis.

Infectious and non-infectious diseases burden among Haitian immigrants in Chile: a cross-sectional study.

Chile has become a popular destination for migrants from South America and the Caribbean (low- and middle-income countries migration). Close to 200.000 Haitian migrants have arrived in Chile. Infectious and non-infectious disease burden among the Haitian adult population living in Chile is unknown. This study aimed to acquire the basic health information (selected transmissible and non-transmissible conditions) of the Haitian adult population living in Chile. A cross-sectional survey was performed, inviting Haitian-born residents in Chile older than 18 years old. Common conditions and risk factors for disease were assessed, as well as selected transmissible conditions (HIV, HBV, and HCV). 498 participants (60.4% female) from 10 communities in two regions of Chile were surveyed. Most subjects had never smoked (91.5%), and 80% drank less than one alcohol unit per month. The mean BMI was 25.6, with 45% of participants having a normal BMI (20-25). Hypertension was present in 31.5% (33% in the 25-44 age group). Prevalence of HIV was 2.4% (95 CI 1.3-4.2%), hepatitis B (HBsAg positive) was 3.4% (95 CI 2.1-5.5%), and hepatitis C was 0% (95 CI 0.0-0.9%). Quality of life showed a significant prevalence of depression and anxiety markers, particularly in those arriving in Chile less than 1 year ago. Low prevalence of obesity, diabetes, smoking, and drinking and estimated cardiovascular risk were found. Nonetheless, hypertension at a younger age, disproportionately higher prevalence of HIV and HBV infection and frequent markers of anxiety and depression were also found. Public policies for detecting and treating hypertension, HIV, and HBV screening, offering HBV vaccination, and organizing mental health programs for Haitian immigrants, are urgently needed.

Immunodeficiency in a Patient with 22q11.2 Distal Deletion Syndrome and a p.Ala7dup Variant in the MAPK1 Gene.

The genetic basis for sporadic immunodeficiency in patients with 22q11.2 distal deletion syndrome is unknown. We report an adult with a type 1 (D-F) 22q11.2 distal deletion syndrome and recurrent severe infections due to herpes zoster virus, presenting mild T cell lymphopenia and diminished frequency of naive CD4+ T cells, but increased frequencies of central, effector, and terminally differentiated memory T cells. Antigen-specific CD4+ and CD8+ T cells to influenza, rotavirus, and SEB were conserved in the patient, but responses to tetanus toxoid were temporarily undetectable. Exomic sequencing identified the c.20_22dupCGG (NM_002745.4) variant in the remaining MAPK1 gene of the patient, which adds 1 alanine to the polyalanine amino-terminal tract of the protein (p.Ala7dup). The mother, unlike the father, was heterozygote for the variant. Western blot analysis with the patient's activated PBMCs showed a 91% reduction in the MAPK1 protein. Further studies will be necessary to determine whether or not the variant present in the remaining MAPK1 gene of the patient is pathogenic.

Encefalopatía epiléptica infantil en un paciente colombiano con una variante patogénica de novo en el gen STXBP1 / Infantile epileptic encephalopathy in a colombian child with a pathogenic de novo STXBP1STXBP1gene variant

El desarrollo de los estudios moleculares ha permitido identificar la etiología genética de diversas enfermedades como las encefalopatías epilépticas infantiles, las cuales se han asociado con variantes patogénicas en diferentes genes, entre ellos el STXBP1. La encefalopatía con epilepsia STXBP1 es una enfermedad genética con un patrón de herencia autosómico dominante, donde están alterados los mecanismos reguladores de la liberación de neurotransmisores por parte de las vesículas sinápticas, con alteración del neurodesarrollo. La edad de presentación del trastorno es temprano, con convulsiones en los primeros dos meses de vida. Los pacientes presentan dificultades en la alimentación, trastornos del movimiento y alteración del espectro autista. En este artículo presentamos el caso clínico de un paciente colombiano con encefalopatía epiléptica STXBP1 revisando los aspectos clínicos de la enfermedad, dirigido a profesionales de la salud para sensibilizarlos y así lograr el diagnóstico temprano. Esta es la primera publicación en el país de un paciente con esta etiología

The development of molecular studies has allowed identifying the genetic cause of various diseases such as infantile epileptic encephalopathy. Several pathogenic variants of different genes have been implicated including the STXBP1 gene. STXBP1 encephalopathy with epilepsy is inherited in an autosomal dominant pattern with disrupted liberation of regulatory mechanisms of neurotransmitters in the synaptic vesicles associated with neurodevelopmental impairments. This condition is characterized by early onset with seizures in the first two months of life. Affected patients may have eating problems, movement disorders and autism spectrum disorders. Herein we present a case of a Colombian infant with STXBP1 encephalopathy with epilepsy. We describe the clinical aspects of the disease to sensitize health care professionals for them to identify this condition and achieve an early diagnosis. This is the first publication in Colombia on a patient featuring this type of etiology.

Assessment of eye drop instillation technique in glaucoma patients.

PURPOSE:: To study the technique of eye drop instillation in glaucoma patients and identify independent factors that may influence their performance. METHODS:: In this cross-sectional study, 71 consecutive patients with glaucoma or ocular hypertension, self-administering topical anti-glaucoma medications for ≥6 months were evaluated. All patients instilled a tear substitute into the eye with the worst eyesight using the technique normally used at home. The following parameters were evaluated: age, number of years receiving treatment with ocular hypotensive eye drops, time spent to instill the first drop, number of drops instilled, correct location of the eye drops, contact of the bottle with the eye, closing of the eyelids or occlusion of the tear punctum, and asepsis of the hands. RESULTS:: The mean age of the patients was 66 ± 10.8 years, and patients were on ocular hypotensive drugs for 11.3 ± 7.3 (range, 2-35) years. Only 28% of the patients were able to correctly instill the eye drops (squeeze out 1 drop and instill it into the conjunctival sac without bottle tip contact). Touching the tip of the bottle to the globe or periocular tissue occurred in 62% of the patients. In 49% of the patients, the eye drops fell on the eyelids or cheek. Two or more drops were squeezed by 27% of the patients. CONCLUSIONS:: The majority of glaucoma patients were unable to correctly instill eye drops. Age was an independent factor associated with eye drop instillation performance.

Assessment of eye drop instillation technique in glaucoma patients / Técnica de instilação de colírio em pacientes com glaucoma

ABSTRACT Purpose: To study the technique of eye drop instillation in glaucoma patients and identify independent factors that may influence their performance. Methods: In this cross-sectional study, 71 consecutive patients with glaucoma or ocular hypertension, self-administering topical anti-glaucoma medications for ≥6 months were evaluated. All patients instilled a tear substitute into the eye with the worst eyesight using the technique normally used at home. The following parameters were evaluated: age, number of years receiving treatment with ocular hypotensive eye drops, time spent to instill the first drop, number of drops instilled, correct location of the eye drops, contact of the bottle with the eye, closing of the eyelids or occlusion of the tear punctum, and asepsis of the hands. Results: The mean age of the patients was 66 ± 10.8 years, and patients were on ocular hypotensive drugs for 11.3 ± 7.3 (range, 2-35) years. Only 28% of the patients were able to correctly instill the eye drops (squeeze out 1 drop and instill it into the conjunctival sac without bottle tip contact). Touching the tip of the bottle to the globe or periocular tissue occurred in 62% of the patients. In 49% of the patients, the eye drops fell on the eyelids or cheek. Two or more drops were squeezed by 27% of the patients. Conclusions: The majority of glaucoma patients were unable to correctly instill eye drops. Age was an independent factor associated with eye drop instillation performance.

RESUMO Objetivo: Avaliar a técnica de instilação de colírio em portadores de glaucoma e identificar fatores independentes que pode influenciar o desempenho. Métodos: Neste estudo transversal 71 pacientes consecutivos com glaucoma ou hipertensão ocular que auto instilam seus colírios há pelo menos 6 meses, foram avaliados. Todos os pacientes instilaram um colírio lubrificante no olho de pior visão utilizando a mesma técnica de instilação de colírio que utilizam rotineiramente em casa. Foram avaliados parâmetros como: idade, número de anos em tratamento com colírios hipotensores oculares, tempo gasto para instilação da primeira gota, número de gotas instiladas, localização correta do colírio, contato do frasco com o olho, fechamento de pálpebras ou oclusão do ponto lacrimal e assepsia das mãos. Resultados: A idade média dos pacientes foi de 66 ± 10,8 anos. Os pacientes esta vam em tratamento com colírios hipotensores oculares por, em média, 11,3 ± 7,3 anos (variando de 2 a 35 anos). Apenas 28% dos pacientes foram capazes de instilar corretamente o colírio (instilação de 1 gota em saco conjuntival sem contato com a ponta do frasco). Contato da ponta do frasco com o olho ou tecido periocular ocorreu em 62% dos pacientes. Em 49% dos casos, o colírio caiu nas pálpebras ou fora do saco lacrimal na primeira tentativa. Duas ou mais gotas foram instiladas por 27% dos pacientes. Conclusão: A maioria dos pacientes com glaucoma é incapaz de instilar o colírio corretamente. A idade é um fator independente que influencia o desempenho da instilação de colírio.

Déficit de pantotenato quinasa asociado a neurodegeneración: reporte de un caso clásico y revisión de la literatura / Pantothenate kinase-associated neurodegeneration: a classical case report and literature review

El déficit de pantotenato quinasa asociado a neurodegeneración (PKAN por su sigla en inglés) es una enfermedadneurodegenerativa poco frecuente que se caracteriza por disfunción extrapiramidal progresiva y acumulaciónde hierro en los ganglios basales. El signo clásico en la neuroimagen de “ojos de tigre” se ve en las imágenesponderadas en T2 en la resonancia magnética cerebral. A continuación presentamos un caso clásico de la enfermedaden un niño que inicia con síntomas motores a los 5 años de edad y que fue estudiado en el Instituto deOrtopedia Infantil Roosevelt, con neuroimágenes típicas y confirmación de la mutación por estudio molecular.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare neurodegenerative disease characterized by progressive extrapyramidal dysfunction and iron accumulation in the basal ganglia. The classic sign in neuroimaging of "eye of the tiger" is seen on T2-weighted magnetic resonance imaging scan. We present a classic case of the disease in a child who starts with motor symptoms at 5 years old and was studied at the Instituto de Ortopedia Infantil Roosevelt, with typical neuroimaging and confirmation of the mutation by molecular study.

Percepção da administração tópica ocular de drogas: aplicador facial x gotas / Topical drug administration perception with and without eye drop applicator

OBJETIVOS: Avaliar por meio de questionário, qual o grau de dificuldade para aplicação tópica de medicações oculares, com ou sem o auxílio do apoio facial. Observar qual método foi tecnicamente melhor utilizado para aplicação de drogas tópicas oculares. MÉTODOS: O estudo foi um ensaio clínico controlado e randomizado, realizado em 50 pacientes no decorrer de 2009 e 2010 na Unidade de Saúde da Família - Lapa. Foi utilizado um frasco de colírio Oftane® e o mesmo foi acoplado ao dispositivo de apoio facial. Cada participante aplicou em cada um dos olhos, a solução com ou sem o uso do dispositivo, sendo que a seleção foi feita através de um processo randomizado. Foi perguntado ao paciente questões pré-formuladas sobre a praticidade de ambos os métodos. RESULTADOS: Considerando o grau de dificuldade de administração tópica ocular: 12 por cento acharam difícil ou muito difícil a aplicação com o objeto de apoio facial e 22 por cento sem o apoio (p=0,0024). As dificuldades descritas pelos pacientes foram relatadas por 22 por cento dos pacientes para aplicação com o dispositivo de apoio facial e por 46 por cento para aplicação sem o mesmo. Já 34 por cento dos pacientes necessitaram de mais de uma instilação para aplicação do colírio sem o apoio, enquanto que 54 por cento dos pacientes precisaram de mais de uma aplicação para que a gota atingisse o olho com o auxílio do apoio facial (p= 0,04). Em 56 por cento dos pacientes houve toque da ponta do colírio com os tecidos oculares, quando o objeto de apoio facial não foi usado, porém quando ele foi utilizado, apenas 2 por cento dos pacientes observados tocaram os tecidos oculares (p=0,0001). CONCLUSÃO: É mais fácil a instilação de colírios com o auxílio do dispositivo de apoio facial. Este também dificulta o contato da ponta do frasco com os tecidos oculares, prevenindo a contaminação do frasco.

OBJECTIVE: Evaluate how difficult it is to apply ocular topical medications with and without an eye dropper facial applicator based on patient observation and answers to a questionnaire. METHODS: The study was a controlled and randomized clinical trial performed in 50 patients during the years of 2009 and 2010 in PSF - Lapa. Eye drops were applied with and without aid of an eye dropper facial applicator. Each individual tested applied randomly on one of their eyes an eye drop with or without the applicator. The patients had to answer questions about the practice concerning both forms of topical eye drug application. RESULTS: 12 percent informed that it was difficult or very difficult to instill eye drops and 22 percent to instill eye drops helped by an eye dropper facial applicator (0,0024). Problems described by patients were considered by 22 percent for eye drops with the applicator and by 46 percent for topical eye drop instillation without it. 34 percent of the patients needed more than one eye drop application to have eye drop contact , while 54 percent of the patients needed more than one application with the eye drop facial applicator in order to get drug eye contact (p= 0,04). In 56 percent of patients there were an eyedropper tip contact with ocular tissues, however there was only 2 percent of contact when the eye drop was instilled aided by the applicator (p=0,0001). CONCLUSION: It is easier to instill an eye drop with the help of an eye dropper applicator than without it. This dispositive also reduces the eyedropper tip contact with the ocular tissues.