RESUMEN
OBJECTIVE: The purpose of this study was to evaluate the lifetime evolution of the radioclinical features in a large family with van Buchem disease. DESIGN AND PATIENTS: The study population included 13 patients, ranging between 6 and 69 years. The evolution of the clinical features has been assessed by retrospective analysis of the clinical records of the patients. The age-related evolution of the cortical hyperostosis and defective modeling at the tubular bones was evaluated by morphometric analysis of hand films in 9 patients, compared with 9 control individuals. Progression of sclerosis of the craniofacial bones was evaluated by analysis of the skull radiographs of eleven van Buchem patients, taken at different age. RESULTS AND CONCLUSIONS: Radioclinical features, including sclerosis of the cranial and tubular bones and cranial nerve deficit, become more prominent in older patients. Defective modeling of tubular bones, cortical thickness and medullary width progress with age. Radioclinical abnormalities of van Buchem patients become more prominent in older patients, which suggests that the van Buchem gene is very actively involved in bone metabolism throughout life. Morphometric analysis of the plain films supports the hypothesis that the physiological function of the van Buchem gene is to inhibit bone formation and possibly to regulate bone remodeling.
Asunto(s)
Enfermedades del Desarrollo Óseo/genética , Enfermedades del Desarrollo Óseo/patología , Adolescente , Adulto , Factores de Edad , Anciano , Enfermedades del Desarrollo Óseo/diagnóstico por imagen , Síndrome de Camurati-Engelmann/diagnóstico por imagen , Síndrome de Camurati-Engelmann/genética , Síndrome de Camurati-Engelmann/patología , Niño , Anomalías Craneofaciales/diagnóstico por imagen , Anomalías Craneofaciales/genética , Anomalías Craneofaciales/patología , Diáfisis , Enfermedades del Nervio Facial/diagnóstico por imagen , Enfermedades del Nervio Facial/genética , Enfermedades del Nervio Facial/patología , Salud de la Familia , Femenino , Predisposición Genética a la Enfermedad/genética , Pérdida Auditiva Conductiva/diagnóstico por imagen , Pérdida Auditiva Conductiva/genética , Pérdida Auditiva Conductiva/patología , Pérdida Auditiva Sensorineural/diagnóstico por imagen , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva Sensorineural/patología , Humanos , Hiperostosis Cortical Congénita/diagnóstico por imagen , Hiperostosis Cortical Congénita/genética , Hiperostosis Cortical Congénita/patología , Masculino , Metacarpo/diagnóstico por imagen , Metacarpo/patología , Persona de Mediana Edad , Países Bajos , Variaciones Dependientes del Observador , Linaje , Estudios Retrospectivos , Esclerosis , Cráneo/diagnóstico por imagen , Cráneo/patología , Estadística como Asunto , Tomografía Computarizada por Rayos XRESUMEN
Adams-Oliver syndrome (AOS) is defined by the combination of limb abnormalities and scalp defects, often accompanied by skull ossification defects. We studied nine families affected with AOS, eight of which have not been clinically described before. In our patients, scalp abnormalities were most often found, followed by limb and skull defects. The most common limb abnormalities appeared to be brachydactyly, syndactyly of toes 2 and 3 and hypoplastic toenails. Additional features observed were cutis marmorata telangiectatica congenita, cryptorchidism and cardiac abnormalities. In an attempt to identify the disease-causing mutations in our families, we selected two genes, ALX4 and MSX2, which were considered serious candidates based on their known function in skull and limb development. Mutation analysis of both genes, performed by direct sequencing, identified several polymorphisms, but no disease-causing mutations. Therefore, we can conclude that the AOS in our set of patients is not caused by mutations in ALX4 or MSX2.