Síndrome de Bardet-Biedl: A propósito de un caso / Bardet-Biedl syndrome: About a case

El síndrome de Bardet-Biedl (SBB) es una entidad poco frecuente, con gran heterogeneidad clínica y genética. Pertenece a las ciliopatías y tiene un modo de herencia autosómico recesivo. Hasta la fecha se han identificado más de 26 genes asociados. Afecta múltiples sistemas con compromiso oftalmológico, renal, cognitivo, esquelético, gonadal y ponderal. Su diagnóstico se basa en criterios clínicos y se confirma mediante estudios genéticos específicos. Presentamos el caso de un paciente de 2 años y 7 meses de edad, con polidactilia, obesidad, retraso del neurodesarrollo y afección renal en quien se arribó al diagnóstico clínico de SBB con posterior confirmación mediante estudio molecular. Se detectó una variante patogénica en homocigosis en el gen BBS2. La sospecha y confirmación diagnóstica permitieron el manejo adecuado del paciente, planificar el seguimiento apropiado y completar el asesoramiento genético familiar

Bardet-Biedl syndrome (BBS) is a rare entity that holds a great clinical and genetic heterogeneity. It is a ciliopathy and has an autosomal recessive inheritance. To this day more than 26 associated genes have been identified. It affects multiple aspects predominantly ophthalmological, renal, cognitive, skeletal, gonadal and weight. The diagnosis is based on clinical criteria and confirmed by specific genetic studies. We describe a case of a 2-year-and 7 month old patient with polydactyly, obe39 sity, neurodevelopmental delay and kidney dysplasia in which clinical diagnosis was suspected by criteria and subsequently has confirmation by molecular study. An homozygous pathogenic variant was detected in the BBS2 gene. The diagnostic suspicion and later confirmation allowed the proper management of this patient as well as an appropriate follow-up and complete genetic family counseling

Síndrome de Bardet Biedl: a propósito de un caso / Bardet Biedl syndrome: a case report

El síndrome de Bardet Biedl es un síndrome genético de herencia autosómica recesiva con compromiso multisistémico y gran variabilidad en su presentación clínica; son características la obesidad, la polidactilia, el hipogonadismo y las alteraciones renales, visuales y cognitivas. Pertenece a las llamadas ciliopatías. El diagnóstico es clínico y puede ser confirmado por estudios genéticos. No existe un tratamiento específico de la patología; se requiere un abordaje multidisciplinario. Se presenta el caso de una paciente de 13 años con obesidad e hiperfagia, diabetes tipo 2, hipotiroidismo, polidactilia, alteraciones del aprendizaje y alteraciones visuales. Se le realizó un panel genético para obesidad en el que se detectaron dos variantes heterocigotas patológicas en el gen BBS2.

Bardet Biedl syndrome is an autosomal recessive ciliopathie. It is a pleiotropic disorder characterised by retinal dystrophy, renal dysfunction, polydactyly, obesity, cognitive deficitand hypogenitalism. Diagnosis is based on clinical features. Molecular genetic testing is available. There is no specific treatment, a multidisciplinary approach is required. We report the case of a 13-year-old female patient with obesity and hyperphagia, type 2 diabetes, hypothyroidism, polydactyly,cognitive deficit and visual impairment. A multigenic panel allowed the identification of two heterozygous pathogenic variants in the BBS2 gene.

Variante patogénica homocigótica del gen BBS10 en un paciente con síndrome de Bardet-Biedl / A pathogenic homozygous variant of the BBS10 gene in a patient with Bardet Biedl syndrome

Resumen El síndrome de Bardet-Biedl es una enfermedad hereditaria, autosómica recesiva, con gran heterogeneidad de locus, que pertenece a las denominadas ciliopatías, denominadas así por la deficiencia funcional presente y porque las proteínas afectadas se localizan en el cilio primario. El síndrome afecta múltiples sistemas, con compromiso visual, renal, cognitivo, esquelético y gonadal, y obesidad. Este síndrome presenta una gran variabilidad intrafamiliar e interfamiliar. Se presenta el caso clínico de un paciente adolescente con diagnóstico de síndrome de Bardet-Biedl, así como su manejo, los resultados de la secuenciación de 22 genes y el análisis actualizado de la literatura médica. Se recopiló la información clínica y, previo consentimiento informado, se hizo la prueba de panel de secuenciación multigénica de los genes implicados. El paciente es hijo de la unión de personas consanguíneas. Fue el primer afectado en la familia y presentaba polidactilia posaxial, obesidad, micropene, retinitis pigmentaria y dificultades de aprendizaje. En el panel multigénico, se identificó la variante patogénica homocigótica c.39_46del en el gen BBS10 y otras variantes de genes BBS asociadas con la obesidad. Dado que el síndrome de Bardet-Biedl es una enfermedad huérfana rara, interpretar el pleiotropismo y la heterogeneidad de locus y de alelos, constituye un reto. La confirmación molecular permite el manejo adecuado de los pacientes, así como el seguimiento y el asesoramiento genético apropiados.

Abstract The Bardet-Biedl syndrome is an autosomal recessive hereditary disorder with vast locus heterogeneity that belongs to the so-called ciliopathies, whose proteins are localized in the primary cilia and present functional deficiency. The multisystemic features of the disease include ocular, renal, cognitive, skeletal, as well as gonadal involvement and obesity, among others, with high inter- and intrafamilial variability. We describe the clinical case of an adolescent male patient with Bardet-Biedl syndrome, including the approach, the results from a 22-gene sequencing panel, and the analysis of updated scientific literature. We collected the clinical data of the patient and, after obtaining the informed consent, we conducted a multigenic sequencing panel oriented to known implicated genes. The patient was born to consanguineous parents and was the first affected member of the family. He presented with postaxial polydactyly, obesity, micropenis, retinitis pigmentosa, and learning disability. The multigenic panel allowed the identification of the homozygous pathogenic variant c.39_46del in the BBS10 gene and in other BBS genes variants associated with obesity. As the Bardet-Biedl syndrome is a rare disease, it is challenging to interpret its pleiotropism and gene/allelic heterogeneity. Its confirmation by molecular tests allows an adequate approach, follow-up, and genetic counseling of the patient and the family.

Report of four cases of Bardet-Biedl syndrome / Relato de quatro casos da síndrome de Bardet-Biedl

Bardet-Biedl syndrome is rare. Although its diagnosis depends on cardinal clinical manifestations which appear in childhood, we report four cases of Bardet-Biedl syndrome lately diagnosed in a dialysis center. Three cases were diagnosed in end-stage renal disease patients when they started maintenance hemodialysis, and one case was diagnosed through screening among hemodialysis patients' relatives. Although pediatricians have more opportunity to diagnose the syndrome, nephrologists are important during the treatment, since renal failure is the main cause of death among Bardet-Biedl syndrome patients. Moreover, late diagnosis of the syndrome among patients with end-stage renal disease can help to detect new cases through the screening among hemodialysis patients' relatives.

A síndrome de Bardet-Biedl é rara. Embora seu diagnóstico seja baseado em manifestações cardinais que aparecem na infância, relatamos quatro casos de síndrome de Bardet-Biedl diagnosticados tardiamente em uma unidade de diálise. Três casos foram diagnosticados em pacientes com doença renal crônica terminal quando iniciaram hemodiálise de manutenção, e um caso diagnosticado por meio de rastreamento dos parentes dos casos em diálise. Embora pediatras tenham mais oportunidade para diagnosticar a síndrome, nefrologistas são importantes durante o tratamento, já que a insuficiência renal é a principal causa de óbito entre os pacientes com síndrome de Bardet-Biedl. Além disso, o diagnóstico tardio da síndrome entre pacientes com doença renal crônica terminal pode ajudar a detecção de casos novos por meio do rastreamento de parentes dos pacientes em hemodiálise.

Pigmentary retinopathy due to Bardet-Biedl syndrome: case report and literature review / Retinopatia pigmentar devido a síndrome de Bardet-Biedl: relato de caso e revisão da literatura

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with clinical and genetic heterogeneity. This syndrome was first described by Laurence and Moon in 1866 and additional cases were described by Bardet and Biedl between 1920 and 1922. The main features are obesity, polydactyly, pigmentary retinopathy, learning disabilities, various degrees of intellectual impairment, hypogonadism, and renal abnormalities. Bardet-Biedl syndrome is both phenotypically and genetically heterogeneous. Clinical diagnosis is based on the presence of 4 of the 5 cardinal features. The authors present a typical case of pigmentary retinopathy due to Bardet-Biedl syndrome and made a brief commentary about the disease's cardinal manifestations.

A síndrome de Bardet-Biedl (BBS) é uma desordem autossômica recessiva rara, com heterogeneidade clínica e genética. Esta síndrome foi descrita pela primeira vez por Laurence e Moon em 1866 e outros casos foram descritos por Bardet e Biedl entre 1920 e 1922. As principais características são obesidade, polidactilia, retinopatia pigmentar, dificuldades de aprendizagem, graus de deficiência intelectual diversos, hipogonadismo e anomalias renais. Síndrome de Bardet-Biedl é fenotipicamente e geneticamente heterogêneos. O diagnóstico clínico baseia-se na presença de quatro dos cinco sinais principais da síndrome. Os autores apresentam um caso típico de retinopatia pigmentar devido à síndrome de Bardet-Biedl e fazem uma breve revisão sobre as manifestações da síndrome com especial atenção à retinopatia pigmentar.