RESUMEN
Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA that produces the farnesylated aberrant lamin A protein, progerin. This multisystem disorder causes failure to thrive and accelerated atherosclerosis leading to early death. Farnesyltransferase inhibitors have ameliorated disease phenotypes in preclinical studies. Twenty-five patients with HGPS received the farnesyltransferase inhibitor lonafarnib for a minimum of 2 y. Primary outcome success was predefined as a 50% increase over pretherapy in estimated annual rate of weight gain, or change from pretherapy weight loss to statistically significant on-study weight gain. Nine patients experienced a ≥50% increase, six experienced a ≥50% decrease, and 10 remained stable with respect to rate of weight gain. Secondary outcomes included decreases in arterial pulse wave velocity and carotid artery echodensity and increases in skeletal rigidity and sensorineural hearing within patient subgroups. All patients improved in one or more of these outcomes. Results from this clinical treatment trial for children with HGPS provide preliminary evidence that lonafarnib may improve vascular stiffness, bone structure, and audiological status.
Asunto(s)
Inhibidores Enzimáticos/uso terapéutico , Farnesiltransferasa/antagonistas & inhibidores , Piperidinas/uso terapéutico , Progeria/tratamiento farmacológico , Piridinas/uso terapéutico , Adolescente , Arterias Carótidas/efectos de los fármacos , Arterias Carótidas/patología , Niño , Preescolar , Diarrea/inducido químicamente , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Inhibidores Enzimáticos/efectos adversos , Inhibidores Enzimáticos/farmacocinética , Farnesiltransferasa/metabolismo , Fatiga/inducido químicamente , Femenino , Humanos , Masculino , Piperidinas/efectos adversos , Piperidinas/farmacocinética , Progeria/patología , Progeria/fisiopatología , Análisis de la Onda del Pulso , Piridinas/efectos adversos , Piridinas/farmacocinética , Resultado del Tratamiento , Vómitos/inducido químicamente , Aumento de Peso/efectos de los fármacosRESUMEN
Seckel syndrome is a rare form of primordial dwarfism that is characterized by short stature, skeletal defects, mental retardation, and characteristic facial features such as microcephaly, micrognathia, and a bird-head appearance. Dental findings include hypodontia, enamel hypoplasia, crowding, and Class II malocclusion. The purpose of this paper was to report the case of a female patient with Seckel syndrome type II and describe her orodental manifestations. She presented with interesting dental findings, including gingival hyperplasia, recession and ulceration, significant crowding, and early exfoliation of the primary dentition with accelerated eruption of the permanent dentition. The patient received comprehensive dental care under general anesthesia, and hard and soft tissue samples were collected for histologic analysis. The patient was followed for over 3 years.