Síndrome de CLOVES: reporte de un caso y revisión de los diagnósticos diferenciales / CLOVES syndrome: case report and review of differential diagnoses

Resumen Presentamos el caso de una paciente de 27 años con diagnóstico reciente de síndrome de CLOVES (Congenital, Lipomatous, Overgrowth, Vascular malformations, Epidermalnevi and Spinal/Skeletalanomalies and/orScoliosisSyndrome), quien fue diagnosticada previamente con los síndromes Klippel-Trenaunay-Weber y de Proteus. El síndrome de CLOVES es una patología poco frecuente y muchas veces el diagnóstico basado en la clínica suele complicarse por la superposición de signos y síntomas con otras patologías que también cursan con sobrecrecimiento.

Abstract We present the case of a 27-years-old patient with a newly diagnosis of CLOVES syndrome (Congenital, Lipomatous, Overgrowth, Vascular malformations, Epidermal nevi and Spinal/Skeletal anomalies and/or Scoliosis Syndrome). She has previously been diagnosed of Klippel-Trenaunay-Weber (at birth) and Proteus Syndrome (at 7 years). She presents dermatological alterations, syndactyly and overgrowth. CLOVES syndrome is a rare disease and often the clinic-based diagnostic is difficult due to overlapping signs and symptoms with other illnesses that also involve overgrowth.

Síndrome de CLOVES: tratamiento con rapamicina oral: reporte de dos casos / CLOVES syndrome: treatment with oral rapamycin: report of two cases

INTRODUCCIÓN: El síndrome de CLOVES se caracteriza por sobrecrecimiento lipomatoso asociado a malformaciones vasculares, representando un desafío diagnóstico y terapéutico. La rapamicina, un inhibidor de la vía mTOR, ha demostrado ser una buena alternativa terapéutica en un grupo de anomalías vasculares. Reportamos dos casos de síndrome de CLOVES con buena respuesta al tratamiento con rapamicina oral. OBJETIVO: Reportar la experiencia del uso de rapamicina oral en el tratamiento de dos pacientes con síndrome de CLOVES. CASOS CLÍNICOS: Caso 1: preescolar femenino de tres años de edad con sín drome de CLOVES e historia de hospitalizaciones reiteradas por infección severa de malformaciones linfáticas macroquísticas y episodios trombóticos. Evoluciona con mala calidad de vida, múltiples hospitalizaciones, riesgo quirúrgico y progresión de las lesiones, por lo que se indicó rapamicina oral. A los 6 meses de tratamiento se evidenció reducción clínica y radiológica del tamaño de las masas lipomatosas y linfáticas, ausencia de linforrea cutánea y mejoría significativa de la calidad de vida, sin requerir nuevas hospitalizaciones. Caso 2: escolar femenino de diez años de edad, portadora de síndrome de CLOVES, que desarrolló escoliosis y deterioro de su capacidad motora, haciéndose dependiente del uso de silla de ruedas. Se indicó rapamicina oral, evidenciándose a los cuatro meses de tratamiento mejoría en su capacidad física, independencia y autovalencia, con desaparición de la linforrea. CONCLUSIÓN: Proponemos la rapamicina oral para el tratamiento de pacientes con sín drome de CLOVES que presenten complicaciones y deterioro de la calidad de vida producto de su enfermedad.

INTRODUCTION: CLOVES syndrome is characterized by lipomatous overgrowth associated with vascular malforma tions, representing a diagnostic and a therapeutic challenge. Rapamycin, an mTOR inhibitor, has proved to be a good therapeutic option in some vascular anomalies. In this article, we report two ca ses of CLOVES syndrome with good response to oral rapamycin treatment. OBJECTIVE: To report the outcome of two patients with CLOVES syndrome treated with oral rapamycin. CLINICAL CASES: Case 1: A three-year-old female preschooler with CLOVES syndrome and history of repeated hospita lizations due to severe infections resulting from macrocystic lymphatic malformations and due to thrombotic episodes. The patient evolved with poor quality of life, multiple hospitalizations, surgical risk and progression of the lesions, therefore, oral rapamycin was indicated. After six months of treatment, clinical and radiological reduction in the size of the lipomatous and lymphatic masses, cutaneous lymphorrhea absence and a significant improvement of her quality of life were observed, without requiring new hospitalizations. Case 2: a ten-year-old female schooler with CLOVES syndro me, who developed scoliosis and deterioration of her motor skills, becoming wheelchair-dependent. Oral rapamycin was indicated, showing improvement in her physical capacity, independence and au tonomy, and absence of lymphorrhea after four months of treatment. CONCLUSION: We propose oral rapamycin for the treatment of patients with CLOVES syndrome who present with complications and deterioration in the quality of life as a result of the disease.

Síndrome de CLOVES / CLOVES syndrome

El síndrome de CLOVES fue recientemente descrito en el 2007 por Sapp et al. y se caracteriza por la presencia de un sobre crecimiento lipomatoso de predominio troncal, malformaciones vasculares, nevo epidérmico y malformaciones esqueléticas, como escoliosis y variables alteraciones espinales. Estos fenómenos determinan su nombre, CLOVES, Congenital, Lipomatous, Overgrowth, Vascular malformations, Epidermal nevi,Skeletal/Scoliosis/Spinal abnormalities. Se produce por una alteración de origen genético, esporádico, pero no necesariamente heredable, secundario a una mutación somática en el periodo embrionario. Se describe un caso clínico de paciente portador de esta patología.

CLOVES syndrome was recently described in 2007 by Sapp et al. and is characterized by the presence of lipomatous growth mainly on trunk, vascular malformations, epidermal nevi, and skeletal malformations such as scoliosis and variables spinal abnormalities. These phenomena determine its name, CLOVES, congenital lipomatous overgrowth, Vascular malformations, Epidermal nevi, Skeletal / Scoliosis / Spinal abnormalities. It is produced by a genetic alteration, sporadic, but not necessarily heritable, CLOVES secondary to a somatic mutation in embryonic period. We described a clinical case of a patient with this condition.

Influência da época de plantio e classes de bulbilhos no rendimento de alho

To evaluate the effects of planting dates and four cloves classes of garlic (Allium sativum L), cultivar Quiteria, one experiment was conducted. The experiment was located in the county of Rio Grande, RS, Brazil. The experimental design was a randomized complete block with four replications and the treatments formed a factorial in split-plot where planting dates formed main plots and clove classes the sub-plots. Significant effects were observed for planting dates, clove class as well as interaction among tratments. Greater bulb yields were observed in the three last planting dates (08/10/87, 08/21/87 and 09/08/87) depending on the clove class used. Within each planting date the effect of class clove was observed. There was significant effects within planting dates and greater yields were observed in classes 1 and 2 (average weight 4.87 and 3.03, respectively).

Avaliaram-se os efeitos de cinco épocas de plantio e quatro classes de bulbilhos sobre o rendimento de alho (Allium sativum L.) , cultivar Quitéria, no município de Rio Grande-RS. O delineamento experimental foi blocos ao acaso com quatro repetições e os tratamentos formaram um fatorial em parcelas subdivididas onde as parcelas constituíram as épocas de plantio e as subparcelas as classes de bulbilhos. Verificaram-se efeitos significativos para os fatores épocas, bulbilhos e interação entre os dois fatores. Os maiores rendimentos ocorreram nos plantios em 10/08/87, 21/08/87 e 08/09/87 dependendo da classe de bulbilhos utilizados. Avaliando-se o efeito de classe de bulbilho dentro de cada época de plantio, verificaram-se diferenças significativas dentro da maioria das épocas de plantio, e os maiores rendimentos foram obtidos utilizando-se bulbilhos com pesos médios de 4,87g e 3,03g.

INFLUÊNCIA DA ÉPOCA DE PLANTIO E CLASSES DE BULBILHOS NO RENDIMENTO DE ALHO

To evaluate the effects of planting dates and four cloves classes of garlic (Allium sativum L), cultivar Quiteria, one experiment was conducted. The experiment was located in the county of Rio Grande, RS, Brazil. The experimental design was a randomized complete block with four replications and the treatments formed a factorial in split-plot where planting dates formed main plots and clove classes the sub-plots. Significant effects were observed for planting dates, clove class as well as interaction among tratments. Greater bulb yields were observed in the three last planting dates (08/10/87, 08/21/87 and 09/08/87) depending on the clove class used. Within each planting date the effect of class clove was observed. There was significant effects within planting dates and greater yields were observed in classes 1 and 2 (average weight 4.87 and 3.03, respectively).

Avaliaram-se os efeitos de cinco épocas de plantio e quatro classes de bulbilhos sobre o rendimento de alho (Allium sativum L.) , cultivar Quitéria, no município de Rio Grande-RS. O delineamento experimental foi blocos ao acaso com quatro repetições e os tratamentos formaram um fatorial em parcelas subdivididas onde as parcelas constituíram as épocas de plantio e as subparcelas as classes de bulbilhos. Verificaram-se efeitos significativos para os fatores épocas, bulbilhos e interação entre os dois fatores. Os maiores rendimentos ocorreram nos plantios em 10/08/87, 21/08/87 e 08/09/87 dependendo da classe de bulbilhos utilizados. Avaliando-se o efeito de classe de bulbilho dentro de cada época de plantio, verificaram-se diferenças significativas dentro da maioria das épocas de plantio, e os maiores rendimentos foram obtidos utilizando-se bulbilhos com pesos médios de 4,87g e 3,03g.