Síndrome de Adams-Oliver y complicaciones asociadas: reporte de una familia en Colombia y revisión de la literatura / Adams-Oliver syndrome and associated complications: Report of a family in Colombia and review of the literature

El síndrome de Adams-Oliver es un trastorno congénito raro, caracterizado por aplasia cutis congénita en el cuero cabelludo, defectos terminales transversales de las extremidades y piel marmorata telangiectásica congénita. Este puede presentarse debido a diferentes patrones de herencia de tipo autosómico dominante o autosómico recesivo, o por mutaciones dominantes de novo. Aunque el síndrome de Adams-Oliver es una enfermedad poco frecuente, es importante conocer sus características clínicas y patrones de herencia, para así establecer un correcto diagnóstico y sus posibles complicaciones durante el seguimiento. En el presente estudio, se describe el caso de una adolescente con síndrome de Adams-Oliver con patrón de herencia autosómica dominante, hipertensión pulmonar y bronquitis plástica. Había varios miembros de su familia con el mismo compromiso

The Adams-Oliver syndrome is a rare congenital disorder characterized by aplasia cutis congenita of the scalp, terminal transverse limb defects, and congenital telangiectatic cutis marmorata. It can occur through different inheritance patterns: autosomal dominant, autosomal recessive, or de novo dominant mutations. Although the Adams-Oliver syndrome is a rare disease, it is essential to know its clinical characteristics and inheritance patterns, to establish a correct diagnosis and its possible complications during follow-up. In the present study, we describe the case of an adolescent with Adams-Oliver syndrome with an autosomal dominant inheritance pattern, pulmonary hypertension and plastic bronchitis, and several compromised family members.

Síndrome de Peutz-Jeghers, telangiectasias y prolapso de la válvula mitral. Presentación de caso y asesoramiento genético / Peutz-Jeghers syndrome, telangiectasias, and mitral valve prolapse. Case presentation and genetic counseling

Introducción: El síndrome de Peutz-Jeghers se caracteriza por hiperpigmentación mucocutánea y hamartomas gastrointestinales que pueden aparecer desde el estómago hasta el ano. Tiene un patrón de herencia autosómico dominante y expresividad variable. El diagnóstico se basa en los hallazgos clínicos y la apariencia histológica de los pólipos. No ha sido reportado hasta ahora asociación de esta entidad a telangiectasias y prolapso de la válvula mitral. Objetivo: Describir los hallazgos que permitieron establecer el diagnóstico de Síndrome de Peutz-Jeghers en un paciente y brindar asesoramiento genético. Presentación del caso: Paciente masculino de 36 años de edad con antecedentes de prolapso de la válvula mitral que acude a consulta de genética clínica con su esposa para solicitar asesoramiento genético, debido a que tienen una hija con diagnóstico de Síndrome de Peutz-Jeghers y desean conocer el riesgo de tener otro hijo afectado. Al examen físico se observa mácula hiperpigmentada en labio inferior y varias de estas en encías. Con tales hallazgos y el antecedente de tener la hija Síndrome de Peutz-Jeghers se emite el mismo diagnóstico en el padre. Como dato de interés se constatan en este individuo múltiples telangiectasias en tórax, cuello y espalda. Los estudios realizados en busca de la causa de estas fueron negativos. Conclusiones: Los antecedentes y los hallazgos encontrados en el paciente permitieron realizar el diagnóstico de Peutz-Jeghers y brindar asesoramiento genético. Se presenta el primer reporte de esta enfermedad asociada a telangiectasias y prolapso de la válvula mitral en la literatura científica(AU)

Introduction: Peutz-Jeghers syndrome is characterized by mucocutaneous hyperpigmentation and gastrointestinal hamartomas that can appear from the stomach to the anus. It has an autosomal dominant inheritance pattern and variable expressiveness. The diagnosis is based on clinical findings and histological appearance of the polyps. No association between this entity and telangiectasias and mitral valve prolapse has been reported so far. Objective: To describe the findings that made it possible to establish the diagnosis of Peutz-Jeghers syndrome in a patient and to provide genetic counseling. Case presentation: Thirty-six-year-old male patient with a history of mitral valve prolapse who attends a clinical genetics consultation with his wife to request genetic counseling due to the fact that their daughter was diagnosed with Peutz-Jeghers Syndrome and they want to know about the risk of having another affected child. On physical examination, a hyperpigmented macule on the lower lip and several of these on the gums were observed. With such findings and the antecedent of having a daughter with Peutz-Jeghers syndrome, the same diagnosis is made in the father. As data of interest, multiple telangiectasias on the thorax, neck and back were found in this individual. The studies carried out to identify the same cause were negative. Conclusions: The history and findings in this patient allowed us to make the diagnosis of Peutz-Jeghers syndrome as well as to provide genetic counselling. The first report of this disease associated with telangiectasias and mitral valve prolapse is presented in the scientific literature(AU)

Estimation of genetic parameters for test-day milk yield in Girolando cows using a random regression model / [Estimação de parâmetros genéticos para produção de leite no dia do teste em vacas da raça Girolando utilizando modelo de regressão aleatória]

The objective of this study was to estimate the components of variance and genetic parameters of test-day milk yield in first lactation Girolando cows, using a random regression model. A total of 126,892 test-day milk yield (TDMY) records of 15,351 first-parity Holstein, Gyr, and Girolando breed cows were used, obtained from the Associação Brasileira dos Criadores de Girolando. To estimate the components of (co) variance, the additive genetic functions and permanent environmental covariance were estimated by random regression in three functions: Wilmink, Legendre Polynomials (third order) and Linear spline Polynomials (three knots). The Legendre polynomial function showed better fit quality. The genetic and permanent environment variances for TDMY ranged from 2.67 to 5.14 and from 9.31 to 12.04, respectively. Heritability estimates gradually increased from the beginning (0.13) to mid-lactation (0.19). The genetic correlations between the days of the control ranged from 0.37 to 1.00. The correlations of permanent environment followed the same trend as genetic correlations. The use of Legendre polynomials via random regression model can be considered as a good tool for estimating genetic parameters for test-day milk yield records.(AU)

O objetivo deste estudo foi estimar os componentes de variância e os parâmetros genéticos da produção de leite no dia do teste (TDMY) em vacas Girolando de primeira lactação, usando modelo de regressão aleatória. Foram utilizados 126.892 registros de produção de leite no dia controle de 15.351 vacas primíparas das raças Holandesa, Gir e Girolando, obtidas na Associação Brasileira dos Criadores de Girolando. Para estimar os componentes de (co) variância, as funções genéticas aditivas e de covariância ambiental permanente foram estimadas por regressão aleatória em três funções: Wilmink, polinômios de Legendre (terceira ordem) e polinômios splines lineares (três nós). A função polinomial de Legendre apresentou melhor qualidade de ajuste. As variâncias genéticas e de ambiente permanente para produção de leite no dia do controle variaram de 2,67 a 5,14 e de 9,31 a 12,04, respectivamente. As estimativas de herdabilidade aumentaram gradativamente do início (0,13) para o meio da lactação (0,19). As correlações genéticas entre os dias do controle variaram de 0,37 a 1,00. As correlações de ambiente permanente seguiram a mesma tendência das correlações genéticas. A utilização dos polinômios de Legendre via modelos de regressão aleatória pode ser considerada como uma boa ferramenta para estimação de parâmetros genéticos da produção de leite no dia do teste.(AU)

Inheritance pattern of molar-incisor hypomineralization

Abstract The aim of this study was to investigate the segregation patterns of molar incisor hypomineralization (MIH) in families, given the evidence that its etiology is influenced by genetics. Clinically, MIH may be detected in parents and/or siblings of MIH-affected children. Our study included children with at least one first permanent molar affected by MIH (proband) and their first-degree relatives (parents and siblings). The participants were examined clinically to detect MIH, according to the European Academy of Paediatric Dentistry criteria (2003). A total of 101 nuclear families (391 individuals) were studied. Proband diagnosis was followed by MIH classification of the subject, his parents and siblings, as affected, unaffected, or unknown. Segregation analysis was performed using the multivariate logistic regression model of the Statistical Analysis for Genetic Epidemiology package, and segregation models (general transmission, environmental, major gene, dominant, codominant and recessive models). The Akaike information criterion (AIC) was used to evaluate the most parsimonious model. In all, 130 affected individuals, 165 unaffected individuals, and 96 unknown individuals were studied. Severe MIH was found in 50.7% of the cases. A segregation analysis performed for MIH revealed the following different models: environmental and dominance (p = 0.05), major gene (p = 0.04), codominant (p = 0.15) and recessive models (p = 0.03). According to the AIC values, the codominant model was the most parsimonious (AIC = 308.36). Our results suggest that the codominant model could be the most likely for inheriting MIH. This result strengthens the evidence that genetic factors, such as multifactorial complex defect, influence MIH.

The polymorphic inheritance of DIO2 rs225014 may predict body weight variation after Graves' disease treatment

ABSTRACT Objective: We aimed to investigate the role of DIO2 polymorphisms rs225014 and rs12885300 in Graves' disease patients, mainly for controlling body weight following treatment. Subjects and methods: We genotyped 280 GD patients by the time of diagnosis and 297 healthy control individuals using a TaqMan SNP Genotyping technique. We followed up 141 patients for 18.94 ± 6.59 months after treatment. Results: There was no relationship between the investigated polymorphisms with susceptibility to GD and gain or loss of weight after GD treatment. However, the polymorphic inheritance (CC+CT genotype) of DIO2 rs225014 was associated with a lower body weight variation after GD treatment (4.26 ± 6.25 kg) when compared to wild type TT genotype (6.34 ± 7.26 kg; p = 0.0456 adjusted for the follow-up time). This data was confirmed by a multivariate analysis (p = 0.0138) along with a longer follow-up period (p = 0.0228), older age (p = 0.0306), treatment with radioiodine (p-value = 0.0080) and polymorphic inheritance of DIO2 rs12885300 (p = 0.0306). Conclusion: We suggest that DIO2 rs225014 genotyping may have an auxiliary role in predicting the post-treatment weight behavior of GD patients.

Caracterización clínico-epidemiológica en pacientes discapacitados visuales por retinosis pigmentaria. Sancti Spíritus. 2009-2019 / Clinical and epidemiological characterization in visual impaired patients due to retinitis pigmentosa. Sancti Spíritus. 2009-2019

RESUMEN Fundamento: La retinosis pigmentaria constituye una causa de discapacidad visual que provoca alteraciones psicológicas y sociales al paciente. Objetivo: Describir las características clínicas y epidemiológicas en pacientes discapacitados visuales por retinosis pigmentaria de la provincia Sancti Spíritus. Metodología: Se realizó un estudio descriptivo, que incluyó 140 pacientes discapacitados visuales afectados por retinosis pigmentaria. Resultados: El grupo etario entre los 29 y 56 años fue el más afectado (78.1 %), el 65 % era del sexo masculino, predominó el color blanco de la piel (87.1 %), sobresalió la catarata como la afección ocular (13.6 %), el 16.4 % presentó hipertensión arterial; la mayoría de los discapacitados no presentó hábitos tóxicos (55 %), prevaleció el debut precoz en el 70 % de los casos. La forma típica de la enfermedad se observó en el 98.5 % de los enfermos, el 67 % manifestó un estadio clínico de la enfermedad grado IV, así como la herencia autosómica recesiva en el 36.4 %. Conclusiones: Predominio de los enfermos en los grupos etario entre 29 y 56 años, masculino, color blanco de la piel; la catarata como patología ocular más frecuente junto a la hipertensión arterial dentro las enfermedades sistémicas; la mayoría de los discapacitados no presentó hábitos tóxicos. El debut precoz, la forma típica, el estadio IV de la enfermedad, así como la herencia autosómica dominante prevalecieron en el estudio.

ABSTRACT Background: Retinitis pigmentosa is a cause of visual impairment that causes psychological and social alterations to the patient. Objective: To describe the clinical and epidemiological characteristics in visual impaired patients due to retinitis pigmentosa in Sancti Spíritus province. Methodology: A descriptive study was carried out, which included 140 visual impaired patients affected by retinitis pigmentosa. Results: The age group between 29 and 56 years old was the most affected (78.1 %), 65 % were male, white skin predominated (87.1 %), cataract stood out as an eye condition (13.6 %), 16.4 % presented arterial hypertension; most of the disabled did not present toxic habits (55 %), early debut prevailed in 70 % of cases. The typical form of the disease was observed in 98.5 % of patients, 67 % showed a clinical stage of grade IV disease, as well as autosomal recessive inheritance in 36.4 %. Conclusions: Prevalence of patients in the age groups between 29 and 56 years, male, white skin color; cataract as the most frequent ocular pathology together with arterial hypertension within systemic diseases; the majority of the disabled patients did not show toxic habits. Early debut, typical form, stage IV disease, and autosomal dominant inheritance prevailed in the study.

Avances en el diagnóstico de la enfermedad granulomatosa crónica: primer estudio familiar en Cuba / Advances in the diagnosis of chronic granulomatous disease: the first family study in Cuba

Introducción: La enfermedad granulomatosa crónica es una inmunodeficiencia primaria causada por mutaciones en la enzima NADPH oxidasa. Esta compromete la producción de especies reactivas del oxígeno, que son importantes contra patógenos. La prueba de la oxidación de la dihidrorodamina es un método eficaz para diagnosticar la enfermedad. Objetivo: Demostrar la utilidad de la prueba de la oxidación de la dihidrorodamina y del patrón de herencia en la confirmación del diagnóstico de la enfermedad granulomatosa crónica de un paciente. Métodos: Estudio de caso de una familia con diagnóstico de enfermedad granulomatosa crónica. Se tomó muestra de sangre periférica para citometría de flujo a tres individuos. Se realizó la prueba de la oxidación de la dihidrorodamina bajo estímulo con acetato de forbolmiristato y se evaluaron las subpoblaciones linfocitarias. Las muestras se leyeron en un citómetro GALLIOS, Beckman Coulter. Los datos obtenidos se analizaron en el programa informático Kaluza. Resultados: El paciente masculino tuvo un valor de oxidación de la dihidrorodamina positiva de 0,87 por ciento, que confirmó un patrón de herencia ligado al cromosoma X; mientras que la madre y hermana gemela portadoras tuvieron valores de 46,76 por ciento y 37,32 por ciento, respectivamente. Se encontraron alteraciones en las subpoblaciones linfocitarias. Conclusiones: La prueba de la oxidación de la dihidrorodamina es un método muy efectivo, rápido y sencillo que confirma el diagnóstico de la enfermedad granulomatosa crónica y determina el patrón de herencia y fenotipo de la enfermedad. Además, permite identificar a las mujeres portadoras según la distribución de los neutrófilos normales y los que tienen el gen CYBB mutado(AU)

Introduction: Chronic granulomatous disease is a primary immunodeficiency caused by mutations in the NADPH oxidase enzymes. This compromises the production of oxygen reactive species, which are important against pathogens. The dihydrorhodamine oxidation test is an effective method for diagnosing the disease. Objective: To demonstrate the usefulness of the dihydrorhodamine oxidation test and the inheritance pattern in confirming the diagnosis of chronic granulomatous disease in a patient. Methods: A case study of a family with a diagnosis of chronic granulomatous disease. A peripheral blood sample was taken from three individuals and by flow cytometry. The dihydrorhodamine oxidation test was performed under stimulation with phorbolmyristate acetate, and lymphocyte subpopulations were evaluated. The samples were read on a GALLIOS, Beckman Coulter cytometer. The data obtained were analyzed using the computer program Kaluza. Results: The male patient had a positive dihydrorhodamine oxidation value of 0.87 percent, which confirmed an inheritance pattern linked to the X chromosome; while the carrier mother and twin sister had values 8203;8203;of 46.76 percent and 37.32 percent, respectively. Alterations were found in the lymphocyte subpopulations. Conclusions: The dihydrorhodamine oxidation test is a very effective, fast and simple method that confirms the diagnosis of chronic granulomatous disease and determines the inheritance pattern and phenotype of the disease. In addition, it allows the identification of female carriers according to the distribution of normal neutrophils and those with the CYBB mutation(AU)

Enfermedad granulomatosa crónica: diagnóstico mediante el ensayo de dihidrorodamina / Chronic granulomatous disease: diagnosis by the dihydrorhodamine assay

Resumen: Introducción: La enfermedad granulomatosa crónica (EGC) se caracteriza por una alteración de la función oxidativa de neutrófilos, presentando herencia ligada al cromosoma X (EGC LX) y autosómica recesiva (EGC AR). El ensayo de dihidrorodamina (DHR) es utilizado para el diagnóstico y detección de portadoras, además proporciona información sobre patrones de herencia. Objetivo: Detectar casos de EGC en niños con infecciones recurrentes y evaluar a sus familiares femeninos mediante el ensayo de DHR, para identificar portadoras y obtener información acerca de posibles patrones de herencia. Pacientes y Método: Fueron incluidos 107 pacientes (<18 años de edad) con sospecha clínica de EGC como neumonías, linfadenopatías y abscesos, remitidos por médicos de hospitales públicos, del 2014 al 2017. Además, se incluyeron seis mujeres, familiares de los niños con EGC. A las muestras de los pacientes se aplicó el ensayo DHR, expresando los resultados como índice de estimulación de neutrófilos (IE). Resultados: La mediana de edad de los pacientes fue de 3 años y 62/107 fueron varones. El IE promedio fue 39,7 ± 13,8 y 101/107 niños exhibieron un cambio completo de fluorescencia de DHR. En 2/107 niños no se observó dicho cambio (IE = 1,0), lo cual indica posible EGC LX, y un tercer niño mostró un leve cambio (IE = 4,8), compatible con EGC AR. En 5/6 mujeres se encontró un patrón bimodal, indicando un estado de portadora. Conclusiones: Fueron detectados tres casos de EGC y cinco portadoras mediante el ensayo de DHR, realizado por primera vez en Paraguay. También se obtuvo información sobre los posibles patrones de herencia, EGC LX en dos familias y un caso probable de EGC AR.

Abstract: Introduction: Chronic granulomatous disease (CGD) is characterized by an alteration of the neutrophil oxidative function. Its inheritance patterns are linked to the X chromosome (X-linked CGD) and autosomal recessive (AR CGD). The dihydrorhodamine (DHR) assay is used for the diagnosis and detection of carriers and provides information on inheritance patterns. Objective: To detect CGD cases in chil dren with recurrent infections and to evaluate their female relatives through the DHR assay to iden tify carriers and obtain information about possible inheritance patterns. Patients and Method: 107 patients (<18 years of age) with clinical suspicion of CGD such as pneumonia, lymphadenopathies, and abscesses were included, referred by physicians from public hospitals between 2014 and 2017. Six female relatives of children with CGD were also included. The DHR assay was performed on all patient samples and the results were expressed as neutrophils stimulation index (SI). Results: The median age of patients was 3 years and 62/107 of them were male. The average SI was 39.7±13.8 and a complete shift of DHR was found in 101/107 children. In 2/107 children, no DHR shift was observed (SI=1.0) indicating possible X-linked CGD, and a third child showed a slight DHR shift (SI=4.8) compatible with AR CGD. 5/6 female relatives presented a bimodal pattern, showing a carrier status. Conclusions: Three cases of CGD and five female carriers were detected through the DHR assay, being the first time that this technique was used in Paraguay. Information on the most likely inheri tance patterns, two X-linked CGD, and one AR CGD case was also obtained.

Psicologia e racismo: as heranças da clínica psicológica / Psychology and racism: the heritage of clinical psychology / Psicología y racismo: la herencia de la clínica psicológica

Resumo Este artigo resulta de pesquisa que investiga como a raça e o racismo afetam a prática dos psicólogos. A partir de uma leitura histórica da construção do que é ser negro no Brasil, discute-se as formas como a Psicologia pode contribuir para o enfrentamento do sofrimento causado pelo racismo. Apoiada na psicanálise e, mais especificamente, no conceito de alianças inconscientes, tal como formulado por René Kaës, investiga-se como profissionais no campo da clínica psicológica identificam (ou não) problemas relacionados ao racismo ao analisar como atuam diante dessa problemática. As entrevistas abertas, baseadas nos pressupostos de Bleger, foram realizadas com três profissionais que atuam com dispositivos clínicos em serviços públicos e privados na região metropolitana de São Paulo. A partir dos registros, discutiu-se como o racismo é transmitido entre as gerações e como opera na clínica. Identificou-se que o sofrimento se expressa por experiências de incerteza ligadas ao corpo, ao desejo, à capacidade profissional em situações que se relacionam com a discriminação, o preconceito e a inferioridade. Observou-se a ambiguidade na diferenciação entre racismo e outros tipos de preconceitos sociais e se destaca o valor da apropriação histórica para que os fenômenos raciais possam ser compreendidos e superados. Este estudo conclui que a atuação da Psicologia se faz necessária de maneira política e social.

Abstract This article is the result of a research that investigates how race and racism affect the practice of psychologists. From a historical interpretation of the construction of what means to be a black person in Brazil, we discuss how Psychology can contribute against the suffering caused by racism. Supported by psychoanalysis and, more specifically, the concept of unconscious alliances as formulated by René Kaës, we investigate how professionals of clinical psychology identify (or not) problems related to racism, analyzing how they act when facing this problem. Open interviews based on Bleger's assumptions were conducted with three professionals who work with clinical devices in public and private services in the metropolitan region of São Paulo. The records were used to discuss how racism is transmitted between generations and how it operates in the clinic, and how suffering is expressed by experiences of uncertainty related to the body, desire and professional ability in situations that refer to discrimination, prejudice and inferiority. There is ambiguity in the differentiation between racism and other types of social prejudice, and the value of historical appropriation is emphasized so that racial phenomena can be understood and overcome. This study concludes that the performance of Psychology is necessary politically and socially.

Resumen Este artículo es el resultado de una investigación que trata cómo la raza y el racismo afectan la práctica de los psicólogos. A partir de una lectura histórica de la construcción de lo que es ser negro en Brasil, discutimos las formas en que la psicología puede contribuir a enfrentar el sufrimiento causado por el racismo. Con el apoyo del psicoanálisis, más específicamente, en el concepto de alianzas inconscientes formulado por René Kaës, investigamos cómo los profesionales en el campo de la clínica psicológica identifican (o no) problemas relacionados con el racismo, analizando cómo actúan frente a ese problema. Las entrevistas abiertas, basadas en los supuestos de Bleger, se realizaron con tres profesionales que trabajan con dispositivos clínicos en servicios públicos y privados en la región metropolitana de São Paulo. De los registros se discutió cómo se transmite el racismo entre generaciones y cómo funciona en la clínica. Se identificó que el sufrimiento se expresa por experiencias de incertidumbre relacionadas con el cuerpo, el deseo, la capacidad profesional en situaciones que se refieren a discriminación, prejuicio e inferioridad. Hay ambigüedad en la diferenciación entre el racismo y otros tipos de prejuicios sociales y se resalta el valor de la apropiación histórica para que los fenómenos raciales puedan ser entendidos y superados. Este estudio concluye que el desempeño de la psicología es necesario política y socialmente.

Osteogénesis imperfecta: revisión de la literatura actual / Osteogenesis imperfecta: review of current literature

La osteogénesis imperfecta (OI) abarca un grupo de enfermedades de origen genético, caracterizadas por un aumento de la fragilidad ósea, debido a una alteración cualitativa y cuantitativa de la masa ósea, que conlleva un riesgo mayor de recurrencia de fracturas y produce deformidades de diversa magnitud, especialmente en los huesos largos. La incidencia en el ámbito mundial es de aproximadamente 1 en 12 000 a 15 000 nacidos vivos. En nuestro país esta patología es poco conocida y además se lleva un sub-registro de los casos que se presentan. Conclusión: La OI es el trastorno hereditario más común del tejido conectivo; en el 90 % de los casos, se debe a las mutaciones de colágeno tipo I. Los tipos I a V son autosómicos dominantes y del VI al XIII son autosómicos recesivos. Las intervenciones terapéuticas existentes no son curativas. El manejo con bifosfonatos puede mejorar significativamente la historia natural de la enfermedad de tipo III y IV.

Osteogenesis imperfecta (OI) covers a group of diseases of genetic origin, is characterized by an increase in fragility of the bones due to a qualitative and quantitative alteration of bone mass, which entails a higher risk of fractures and produce deformities specially of long bones. The incidence worldwide is approximately 1 in 12,000 to 15,000 live births. In our country this pathology is little known and there is an under-reporting of OI cases. Conclusion: OI is the most common inherited disorder of connective tissue. 90% is due to mutations of type I collagen. Type I to type V are autosomal dominant and type VI to type XIII are autosomal recessive. The existing therapeutic interventions are not curative. Management with bisphosphonates can improve the natural history of type III and type IV disease.

Hallazgos clínicos, bioquímicos y moleculares de la acidemia propiónica / Clinical, biochemical and molecular findings of propionic acidemia

La acidemia propiónica es un trastorno infrecuente con patrón de herencia autosómico recesivo causado por la deficiencia de la enzima mitocondrial propionil-CoA carboxilasa, que convierte el propionil-CoA a D-metilmalonil-CoA. Se expone el caso de un recién nacido masculino con signos de dificultad respiratoria, vómitos y cansancio durante la alimentación. Presentó acidosis metabólica, cuerpos cetónicos en el suero y la orina positivos, hiperamonemia, anemia, trombocitopenia e hipoproteinemia. El estudio bioquímico por cromatografía de gases acoplada a espectrometría de masas en la muestra de orina fue sugestivo de acidemia propiónica. El estudio molecular en el gen PCCA encontró las mutaciones c.893A>G (p.K298R) en el padre y c.937C>T (p.R313X) en la madre. Existe la necesidad de establecer el diagnóstico de esta entidad infrecuente para implementar las medidas terapéuticas disponibles y aportar el oportuno asesoramiento genético.

Propionic acidemia is an infrequent disorder with an autosomal recessive inheritance pattern caused by the deficiency of the mitochondrial enzyme propionyl-CoA carboxylase that converts propionyl-CoA to D-methylmalonyl-CoA. We present the case of a male newborn who showed signs of respiratory distress, vomiting and tiredness during feeding. He presented metabolic acidosis, positive serum and urine ketone bodies, hyperammonemia, anemia, thrombocytopenia and hypoproteinemia. The biochemical study by gas chromatography coupled to mass spectrometry in a urine sample was suggestive of propionic acidemia. The molecular study in the PCCA gene found the mutations c.893A>G (p.K298R) in the father and c.937C> T (p.R313X) in the mother. There is a need to establish the diagnosis of this infrequent entity to implement the therapeutic measures available and provide the appropriate genetic counseling.

Reproductive alternatives for patients with dystrophic epidermolysis bullosa / Opções reprodutivas para pacientes com epidermólise bolhosa distrófica

ABSTRACT Epidermolysis bullosa describes a group of skin conditions caused by mutations in genes encoding proteins related to dermal-epidermal adhesion. In the United States, 50 cases of epidermolysis bullosa per 1 million live births are estimated, 92% of which classified as simplex, 5% dystrophic, 1% junctional and 2% non-classified. Dystrophic epidermolysis bullosa is associated with autosomal, dominant and recessive inheritance. Epidermolysis bullosa causes severe psychological, economic and social impacts, and there is currently no curative therapy, only symptom control. Embryonic selection is available for epidermolysis bullosa patients in order to prevent perpetuation of the condition in their offspring.

RESUMO O termo "epidermólise bolhosa" descreve um grupo de afecções cutâneas causadas por mutações em genes que codificam proteínas relacionadas à aderência dermoepidérmica. Nos Estados Unidos, estima-se a ocorrência de 50 casos de epidermólise bolhosa por 1 milhão de nascidos vivos, sendo 92% deles da forma simples, 5% da forma distrófica, 1% da forma juncional e 2% não classificados. A epidermólise bolhosa do tipo distrófica foi associada a padrões autossômicos, dominante e recessivo. A epidermólise bolhosa causa sérios impactos psicológicos, econômicos e sociais, e não há tratamento curativo atualmente − apenas controle dos sintomas. A seleção embrionária é disponível para portadores de epidermólise bolhosa, a fim de evitar a perpetuação da condição em seus descendentes.

Diversity of clinical, radiographic and genealogical findings in 41 families with amelogenesis imperfecta

Abstract Amelogenesis imperfecta (AI) is a group of enamel development disorders that alter the structure and chemical composition of the tissue. There is great variability in the clinical presentation; according to Witkop, AI can be categorized into 14 subtypes, which makes its diagnosis extremely complex. Objective: This study aimed to describe and determine the frequency of clinical and radiographic features and inheritance patterns found in 41 Chilean families diagnosed with diverse types of AI. Material and Methods: We analyzed the clinical records, photographs, pedigrees and radiographs of 121 individuals recruited between 2003 and 2016. All of the information was included in a database that was analyzed using the application Stata 14. Results: The 72 affected individuals had average age of 16 years, and no sex association with the presence of AI was found. The most frequent clinical subtypes were as follows: 43% hypomature, 25% hypoplastic, 21% hypomature/hypoplastic, 7% hypocalcified and 4% hypocalcified/hypoplastic. The number of severely affected teeth was 22, which occurred in the patients with hypocalcified and hypocalcified/hypoplasic AI who presented the highest number of damaged teeth. Caries and periodontal disease were found in 47 and 32% of the patients, respectively. Malocclusions were observed in 43% of the individuals with AI, with open bite being the most frequent. Radiographically, the thickness of the enamel decreased in 51% of the patients, and 80% showed decreased radiopacity of the enamel compared to that of dentin. Autosomal dominant inheritance pattern was found in 37% of the families with hypoplastic AI, and autosomal recessive pattern was present in 56% of the other clinical subtypes, but more frequently in those affected with hypomature and hypocalcified AI. Conclusion: Of the five clinical subtypes, autosomal recessive hypomature, autosomal dominant hypoplastic and autosomal recessive hypomature/hypoplastic AI were the most prevalent subtypes in this group.

Hereditary melanoma: a five-year study of Brazilian patients in a cancer referral center - phenotypic characteristics of probands and pathological features of primary tumors

Abstract: BACKGROUND: Approximately five to 10% of all melanomas occur in families with hereditary predisposition and the main high-risk melanoma susceptibility gene is the CDKN2A. OBJECTIVES: To describe, after a five-years study, the clinical data of patients (probands) from familial melanoma kindreds, and the pathological characteristics of their melanoma. METHODS: The inclusion criteria were melanoma patients with a family history of melanoma or pancreatic cancer (first- or second-degree relatives) or patients with multiple primary melanomas (MPM). RESULTS: A total of 124 probands were studied, where 64 were considered familial cases and 60 MPM. Mean age at diagnosis was 50 years. Our results show that the following characteristics were prevalent: skin phototype I/II (89.5%), sunburn during childhood (85.5%), total number of nevi ≥50 (56.5%), Breslow thickness ≤1.0mm (70.2%), tumors located on the trunk (53.2%) and superficial spreading melanomas (70.2%). STUDY LIMITATIONS: Analyses of probands' relatives will be demonstrated in future publication. CONCLUSIONS: Our findings are in agreement with previous familial melanomas reports. Fifteen new melanomas in 11 patients were diagnosed during follow up, all of which were ≤1.0 mm. This is the largest dataset of Brazilian melanoma prone kindreds to date, thus providing a complete database for future genetic studies.

Inimigas da pátria: Propostas educativas para a guerra contra as doenças venéreas na Marinha do Brasil nas décadas de 1920 e 1930 / Homeland enemies: Educational proposals for the war against venereal diseases in the Brazilian Navy in the 1920s and 1930s / Enemigas de la patria: Propuestas educativas para la guerra contra las enfermedades venéreas en la Marina de Brasil en las décadas de 1920 y 1930

Resumo Este artigo oferece reflexões preliminares acerca de propostas educativas voltadas ao combate das doenças venéreas na Marinha de Guerra divulgadas em duas obras de médicos militares nas décadas de 1920 e 1930 no Brasil: Doenças no Mundo (1923), de autoria do médico e capitão-de-corveta João Pires Porto-Carrero, e Moléstias Venéreas na Marinha brasileira (1933), escrito pelo médico e capitão-de-mar-e-guerra Artur do Valle Lins. Para tanto, a análise desdobrou-se em dois aspectos centrais: os debates nacionais acerca das doenças venéreas como empecilhos à construção da nação brasileira, e a presença destes nas propostas educativas divulgadas nos livros produzidos por médicos militares que tematizaram o combate às doenças venéreas na Força Naval brasileira. Por meio da análise dessas publicações pôde-se perceber uma íntima relação entre eugenia, sanitarismo e a luta contra tais doenças em meio a um projeto de construção da nação brasileira, algo que não esteve presente somente nas propostas educativas do exército, mas perpassou os debates nacionais da área médica.

Abstract This article offers preliminary reflections about educational proposals aimed at the combat of venereal diseases in the Navy, disseminated in two works by military doctors in the 1920s and 1930s in Brazil: Diseases in the World (1923), by the doctor and Captain-of-Corvette João Pires Porto-Carrero, and Venereal Diseases in the Brazilian Navy (1933), written by the doctor and Captain-of-Sea-and-War Artur do Valle Lins. The analysis focuses on two central aspects: the national debates about venereal diseases as obstacles to the construction of a Brazilian nation, and their presence in educational proposals presented in books produced by military doctors about the fight against venereal diseases in the Brazilian Naval Force. Through the analysis of these publications, it was possible to notice an intimate relationship between eugenics, sanitarism and the fight against such diseases in the context of a construction project in the Brazilian nation, something that was present not only in the educational army proposals, but has also permeated national debates in the medical field.

Resumen Este artículo presenta reflexiones preliminares acerca de propuestas educativas dirigidas al combate de las enfermedades venéreas en la Marina de Guerra divulgadas en Brasil en dos obras de médicos militares, en las décadas de 1920 y 1930: Enfermedades en el Mundo (1923), de autoría del médico y Capitán-de-Corveta João Pires Porto-Carrero, y Molestias Venéreas en la Marina brasileña (1933), escrito por el médico y Capitán-de-Mar-y-Guerra Artur do Valle Lins. Con ese propósito, el análisis focalizó en dos aspectos centrales: los debates nacionales sobre las enfermedades venéreas como impedimentos a la construcción de la nación brasileña, y la presencia de éstas en las propuestas educativas divulgadas en los libros producidos por médicos militares, que tematizaron el combate a las enfermedades venéreas en la Fuerza Naval del Brasil. Fue identificada una íntima relación entre eugenia, sanitarismo y la lucha contra tales enfermedades en el contexto de un proyecto de construcción de nación, algo que no solo estuvo presente en las propuestas educativas del ejército, sino que traspasó los debates nacionales del área médica.

Pedigree Analysis and Audiological Investigations of Otosclerosis: An Extended Family Based Study

BACKGROUND AND OBJECTIVES: To analyse the audiometric profile and the pedigree of a large family with otosclerosis to understand the inheritance pattern and its implication in clinical management of the disease. SUBJECTS AND METHODS: Pedigree analysis was performed on the basis of family history and audiometric tests. Pure tone audiometry, tympanometry, and acoustic reflexes were evaluated for the family members. Audiometric analysis was also carried out for the individuals who have already underwent corrective surgery at the time of study. RESULTS: Out of 112 family members, 17 were affected individuals, and 11 of them were surgically confirmed. Hearing loss (HL) started unilaterally and progressed to bilateral form. Otosclerosis was presented in early 20’s in the first and second generations but it was delayed to mid-late 30’s in the fourth generation. An affected female was diagnosed with otosclerosis during her pregnancy. Though the disease was familial, a mother of four affected offspring in this family did not develop otosclerosis until she died at the age of 84. CONCLUSIONS: The five-generation family, which was analysed in the present study, exhibited autosomal dominant inheritance of otosclerosis with reduced penetrance. Bilateral HL and pregnancy-aggravated otosclerosis were observed in this family. It was found for the first time that the age of onset of the disease delayed in the successive generations. The current study indicated the importance of detailed pedigree analysis for better clinical management of otosclerosis.

Primary Autosomal Recessive Distal Renal Tubular Acidosis Caused by a Common Homozygous SLC4A1 Mutation in Two Lao Families

Primary distal renal tubular acidosis (dRTA) caused by mutations of the SLC4A1 gene, which encodes for erythroid and kidney isoforms of anion exchanger, shows marked difference in inheritance patterns and clinical features in different parts of the world. While the disease shows autosomal dominant inheritance without any red cell morphological abnormalities in the temperate countries, it is almost invariably recessive, and often accompanies red cell morphological abnormalities or hemolytic anemia in the tropics, especially in Southeast Asia. Here, we report three patients with autosomal recessive (AR) dRTA, presenting with typical findings of failure to thrive and rickets, from two unrelated Lao families. The mutational analyses revealed that all three patients harbored the same homozygous SLC4A1 mutation, p.Gly701Asp. Adequate supplementation of alkali and potassium resulted in remarkable improvement of growth retardation and skeletal deformities of the patients. This is the first case report of Lao patients with AR dRTA caused by SLC4A1 mutations.

Caracterização oncogenética da história familiar de mulheres diagnosticadas com tumores de endométrio proficientes para o sistema de reparo de pareamento incorreto de DNA / Oncogenetic characterization of the family history of women diagnosed with endometrial tumors proficient for the DNA mismatch repair system

Os tumores de endométrio fazem parte do espectro de tumores de inúmeras síndromes neoplásicas hereditárias (SNH). Entretanto, tais tumores, quando proficientes para o sistema de reparo incorreto de DNA (MMR), geralmente são classificados como cânceres esporádicos. Contudo, mesmo diante de uma provável classificação esporádica, a história familiar (HF) de portadoras dessas neoplasias pode apresentar indícios de componentes genéticos hereditários associados ao seu desenvolvimento. Para tanto, tivemos como objetivo principal, caracterizar a HF de mulheres diagnosticadas com tumores de endométrio, com estabilidade de microssatélites, proficientes para o sistema de reparo de pareamento incorreto de DNA, com a finalidade de avaliar o seu risco para síndromes neoplásicas hereditárias. Trata-se de um estudo descritivo de caráter populacional. A amostra inicial (n=58) foi acessada e caracterizada por meio da colaboração com um estudo maior, que investigou tumores de endométrio, quanto à proficiência do sistema de reparo MMR em uma casuística brasileira, a partir de dados coletados no biobanco do Serviço de Patologia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. A coleta da HF teve início em abril de 2018 e foi finalizada em julho do mesmo ano. Nossa casuística final foi composta por 42 mulheres que atenderam aos critérios de inclusão/exclusão. Por meio de contato telefônico foi aplicado o Questionário de Rastreamento Primário e, posteriormente, desenhado o heredogramas das famílias, com a utilização do software PedigreeDraw. Após a coleta e o registro da HF, os heredogramas foram analisados pela pesquisadora principal deste trabalho e as famílias foram classificadas quanto ao seu risco de possuírem uma SNH. Nosso estudo possibilitou a identificação de 27 mulheres (64% da nossa casuística) que podem estar em risco para SNH. Dentre essas, no que se refere às SNH que têm o câncer colorretal no seu espectro de tumores, 26% preencheram critérios de Bethesda e 15% preencheram critérios de Amsterdam, sendo que 4% preencheram critérios para FAP atenuada. Já 11% preencheram critérios para síndrome de Câncer de Mama e Ovário Hereditários e 22% preencheram critérios para síndrome Li-Fraumeni Like tipo 1. Ressaltamos que 33% apresentaram história pessoal de câncer abaixo dos 50 anos. Os resultados aqui apresentados reforçam a importância da HF e precisam encorajar os profissionais de saúde a realizar com maior frequência a coleta e o registro da HF, ainda que seja autorreferida. Mesmo diante das novas tecnologias genômicas e do crescente conhecimento dos aspectos genéticos e de testes, a HF continua a destacar informações de risco, extremamente significativas, que vão além da suscetibilidade genética. Portanto, os indivíduos e suas famílias devem ser acompanhados com base na história pessoal e familiar para identificação de suspeitas de SNH

Endometrial tumors are part of the spectrum of tumors of innumerable hereditary neoplastic syndromes (SNH). However, such tumors, when proficient for the DNA mismatch repair (MMR), are usually classified as sporadic cancers. However, even though they are characterized as sporadic, the family history (HF) of carriers of these neoplasms may present evidence of hereditary genetic components associated with its onset and development. In order to study such evidences, we aimed to characterize the HF of women diagnosed with endometrial tumors and microsatellite stability, proficient for the DNA mismatch repair system, in order to evaluate their risk for hereditary neoplastic syndromes. This is a descriptive population-based study. The initial sample (n = 58) was reached and characterized by collaboration with a larger study, which investigated endometrial tumors, regarding the proficiency of the MMR system in a Brazilian sample. We collected data in the Pathology Center of the Hospital das Clínicas of the Medical School of Ribeirão Preto of the University of São Paulo. The HF collection began in April 2018 and was completed in July of the same year. Our final sample consisted of 42 women who met the inclusion / exclusion criteria. By telephone, the Primary Tracking Questionnaire was applied and, afterwards, the families' pedigrees were drawn using the PedigreeDraw software. After HF collection and registration, the pedigrees were analyzed by the main researcher of this study and the families were classified according to their risk of having an NHS. Our study allowed the identification of 27 women (64% of our sample) who may be at risk for SNH. For samples who have colorectal cancer in their tumor spectrum and suspicion for NHS, 26% met Bethesda criteria and 15% met Amsterdam criteria, and 4% met criteria for attenuated FAP. 11% of our sample met criteria for Hereditary Breast and Ovarian Cancer syndrome and 22% met criteria for Li-Fraumeni Like type 1 syndrome. We pointed out that 33% had a personal history of cancer under 50 years. The results presented here support the importance of HF and the need to encourage health professionals to perform HF collection and registration more frequently, even if it is self-referenced. Even in the face of new genomic technologies and growing knowledge of genetic and testing aspects, HF continues to highlight extremely significant risk information beyond genetic susceptibility. Therefore, not only the individuals but also their families should be monitored on the basis of personal and family history to identify suspected SNH

Antecedentes familiares y diagnóstico bioquímico en 1948 formadores de cálculos renales / Family history and biochemical diagnosis in 1948 kidney stone formers

INTRODUCTION: The presence of family history of nephrolithiasis is associated with an increased risk of renal lithiasis. Different epidemiological studies have shown a family component in the incidence of it, which is independent of dietary and environmental factors. The role of heredity is evident in monogenic diseases such as cystinuria, Dent's disease or primary hyperoxaluria, while a polygenic inheritance has been proposed to explain the tendency to form calcium oxalate stones. OBJECTIVE: Our objective was to evaluate the family history of patients with renal lithiasis and the correlation of family history with its corresponding biochemical alteration, considering only those with a single metabolic alteration. METHODS: a prospective and retrospective observational and analytical study that included 1948 adults over 17 years of age and a normal control group of 165 individuals, all evaluated according to an ambulatory protocol to obtain a biochemical diagnosis. They were asked about their family history of nephrolithiasis and classified into five groups according to the degree of kinship and the number of people affected in the family. RESULTS: a positive family history of nephrolithiasis was found in 27.4% of renal stone formers, predominantly in women, compared to 15.2% of normal controls. The family history of nephrolithiasis was observed especially in 31.4% of patients with hypomagnesuria and in 29.6% of hypercalciuric patients. The rest of the biochemical alterations had a positive family history between 28.6% in hyperoxaluria and 21.9% in hypocitraturia. The highest percentage of family history of nephrolithiasis was found in cystinuria (75%) although there were few patients with this diagnosis. CONCLUSIONS: the inheritance has a clear impact on urolithiasis independently of the present biochemical alteration. Family history of nephrolithiasis of the first and second degree was observed between 21 and 32% of patients with renal lithiasis, with hypercalciuria and hypomagnesuria being the biochemical alterations with more family history

INTRODUCCIÓN: La presencia de antecedentes familiares de nefrolitiasis se asocia con un mayor riesgo de litiasis renal. Diferentes estudios epidemiológicos han mostrado un componente familiar en la incidencia de la misma, que es independiente de los factores dietéticos y ambientales. El papel de la herencia es evidente en enfermedades monogénicas como la cistinuria, la enfermedad de Dent o la hiperoxaluria primaria, mientras que se ha propuesto una herencia poligénica para explicar la tendencia a la formación de cálculos de oxalato de calcio. OBJETIVO: Nuestro objetivo fue evaluar la historia familiar de los pacientes con litiasis renal y la correlación de los antecedentes familiares con su correspondiente alteración bioquímica, considerando solo aquellos con una única alteración metabólica. MATERIAL Y MÉTODOS: Estudio observacional y analítico prospectivo y retrospectivo que incluyó a 1948 adultos mayores de 17 años y un grupo control normal de 165 individuos, evaluados todos siguiendo un protocolo ambulatorio para obtener un diagnóstico bioquímico. Se les preguntó acerca de su historia familiar de nefrolitiasis y se clasificó en cinco grupos según el grado de parentesco y el número de personas afectadas en la familia. Resultados: Se encontró historia familiar positiva de nefrolitiasis en el 27,4% de los formadores de cálculos renales, predominando en mujeres, frente al 15,2% de los controles normales. La historia familiar de nefrolitiasis se observó especialmente en el 31,4% de los pacientes con hipomagnesuria y en el 29,6% de los hipercalciúricos. El resto de las alteraciones bioquímicas tuvo antecedentes familiares positivos entre el 28,6% en la hiperoxaluria y el 21,9% en la hipocitraturia. El porcentaje más alto de antecedentes familiares de nefrolitiasis se encontró en la cistinuria (75%) aunque hubo pocos pacientes con este diagnóstico. CONCLUSIONES: La herencia tiene un claro impacto en la urolitiasis independientemente de la alteración bioquímica presente. Se observan antecedentes familiares de nefrolitiasis de primer y segundo grado entre el 21 y 32% de los pacientes con litiasis renal, siendo la hipercalciuria y la hipomagnesuria las alteraciones bioquímicas con más antecedentes familiares