[Hirschsprung's disease and medullary carcinoma of the thyroids: two diseases in a monogenetic disorder]. / La enfermedad de Hirschsprung y el carcinoma medular de tiroides: dos enfermedades en una alteración monogénica.

INTRODUCTION: The most common gene involved in Hirschsprung's disease (HD) is protooncogene RET. More than 100 mutations of this gene have been described associated with HD. The mutations that change a cysteine with another aminoacid (mainly in exons 10 and 11) give a risk of familial medullary thyroid carcinoma (FTMC) and MEN 2A. These mutations are found in 5% of patients with HD and have an autosomal dominant inheritance. The FTMC is aggressive and the prophylactic thyroidectomy is the best treatment. We present our results in screening for RET protooncogene mutations associated with TMC in patients with HD. PATIENTS AND METHODS: We have treated 40 patients with HD in the last 15 years. We have classified the patients into two groups: A) high risk of RET protooncogene mutation associated with FTMC (family history of HD, long-segment and/or associated syndromes) and B) low risk (rectosigmoid involvement). We have identified the exons 7, 8, 9, 10, 11, 13, 14 and 15 of the RET protooncogene in 12 of 15 children from group A and 6 from 25 from group B. RESULTS: We have found the p.Cys620Ser mutation (exon 10) in a girl from group A (long-segment). In the family study, we have found the same mutation in her mother, her oncle and her cousin. CONCLUSION: The comprehensive management of children with HD requires screening for RET protooncogene mutations associated with FTMC. In the first-degree relatives of children with a mutation risk, screening is required.

[Uveitis masquerade syndrome as a presenting form of diffuse retinoblastoma]. / Síndrome Mascarada por retinoblastoma difuso.

CLINIC REPORT: A 3-year-old boy presented with an intermediate uveitis. Complete ophthalmic exam, ocular ultrasonography, magnetic resonance imaging and computerized tomography of the orbit were inconclusive. Determination of the aqueous humor/serum rate of Lactate dehydrogenase (LDH) was the key for the diagnosis of a diffuse retinoblastoma. DISCUSSION: A masquerade syndrome is the initial presentation in 1-3% of retinoblastomas. Aqueous humor punction is contraindicated in patients with retinoblastoma but it might be the only way to achieve a correct diagnosis in these difficult and very unusual cases: enzymatic assays such as LDH offer a good sensitivity and specificity for the diagnosis of these patients.

Síndrome mascarada por retinoblastoma difuso / Uveitis masquerade syndrome presenting as a diffuse retinoblastoma

Caso clínico: Paciente de tres años con sospecha deuveítis intermedia. La exploración oftalmológica,ecografía ocular, resonancia nuclear magnética ytomografía computerizada orbitaria no fueron concluyentes.La determinación de la tasa de lactatodeshidrogenasa (LDH) en humor acuoso/suero fuela clave para llegar al diagnóstico de un retinoblastomadifuso.Discusión: El síndrome mascarada es la forma dedebut en un 1-3% de los retinoblastomas. La punciónde cámara anterior está contraindicada enpacientes con retinoblastoma pero podría ser la únicaforma de llegar a un diagnóstico correcto enestos casos difíciles y poco frecuentes. Las pruebasenzimáticas como la LDH nos ofrecen una buenasensibilidad y especificidad para el diagnóstico de estos pacientes(AU)

Clinic report: A 3-year-old boy presented with anintermediate uveitis. Complete ophthalmic exam,ocular ultrasonography, magnetic resonance imagingand computerized tomography of the orbitwere inconclusive. Determination of the aqueoushumor/serum rate of Lactate dehydrogenase (LDH)was the key for the diagnosis of a diffuse retinoblastoma.Discussion: A masquerade syndrome is the initialpresentation in 1-3% of retinoblastomas. Aqueoushumor punction is contraindicated in patients withretinoblastoma but it might be the only way toachieve a correct diagnosis in these difficult andvery unusual cases: enzymatic assays such as LDHoffer a good sensitivity and specificity for the diagnosisof these patients(AU)

La enfermedad de Hirschsprung y el carcinoma medular de tiroides: dos enfermedades en una alteración monogénica / Hirschsprung’s disease and medullary carcinoma of the thyroids: Two diseases in a monogenetic disorder

Introducción. Las mutaciones del protooncogén RET son las más frecuentes en la enfermedad de Hirschsprung (EH). Hay descritas más de 100 mutaciones de este gen asociadas a EH, pero aquellas en que el error reemplaza una cisteína por otro aminoácido (principalmente en exones 10 y 11) presentan riesgo de MEN 2A y carcinoma medular de tiroides familiar (CMTF). Estas mutaciones de riesgo se hallan en un 5% de los pacientes con EH y presentan una herencia autosómica dominante. El CMTF tiene un comportamiento agresivo y la tiroidectomía profiláctica es el mejor tratamiento. Presentamos nuestros resultados en el cribado de las mutaciones del gen RET asociado a CMT en pacientes afectos de EH. Pacientes y método. Se han tratado en nuestro hospital 40 pacientes con EH en los últimos 15 años. Hemos clasificado a los pacientes en dos grupos: A) alto riesgo de mutación del gen RET asociada a CMTF (antecedentes familiares de EH, segmento largo y/o síndromes asociados) y B) bajo riesgo (afectación rectosigmo idea exclusiva).Se han determinado los exones 7, 8, 9, 10, 11, 13, 14 y 15 del protooncogén RET en 12/15 niños del grupo A y en 6/25 del grupo B. Resultados. Una niña del grupo A presenta la mutación p.Cys620Ser (exón 10). En el estudio familiar se ha encontrado esta misma mutación en la madre, el tío materno y una de sus hijas. Conclusiones. El manejo integral de los niños con EH exige el despistaje de mutaciones del gen RET asociadas a CMTF. En los familiares de primer grado de los niños con una mutación de riesgo, el cribado es obligatorio (AU)

Introduction. The most common gene involved in Hirschsprung’s disease (HD) is protooncogene RET. More than 100 mutations of this gene have been described associated with HD. The mutations that change a cysteine with another aminoacid (mainly in exons 10 and 11) give a risk of familial medullary thyroid carcinoma (FTMC) and MEN 2A. These mutations are found in 5% of patients with HD and have an autosomal dominant inheritance. The FTMC is aggressive and the prophylactic thyroidectomy is the best treatment. We present our results in screening for RET protooncogene mutations associated with TMC in patients with HD. Patients and methods. We have treated 40 patients with HD in the last 15 years. We have classifi ed the patients into two groups: A) high risk of RET protooncogene mutation associated with FTMC (family history of HD, long-segment and/or associated syndromes) and B) low risk (rectosigmoid involvement).We have identified the exons 7, 8, 9, 10, 11, 13, 14 and 15 of the RET protooncogene in 12 of 15 children from group A and 6 from 25 from group B. Results. We have found the p.Cys620Ser mutation (exon 10) in a girl from group A (long-segment). In the family study, we have found the same mutation in her mother, her oncle and her cousin. Conclusion. The comprehensive management of children with HD requires screening for RET protooncogene mutations associated with FTMC. In the fi rst-degree relatives of children with a mutation risk, screening is required (AU)