[Familial expansive osteolysis otological and dental manifestations of genetic origin].
OBJECTIVE
Familial Expansive Osteolysis (FEO) ist a rare autosomal dominant bone dysplasia. The disease can show general and focal skeletal alterations, the latter having a predominantly peripheral distribution. Onset occurs after the second decade of life.


METHODS
We present the study, of 30 years, of a family consisting of 49 members covering five generations.


RESULTS
Among the 35 members studied, 18 have familial expansive osteolysis (FEO). The first clinical sign of the condition is transmission deafness at an early age. The features of the teeth has a unique and characteristic appearance. Thinning of the cortical bone leads to severe, painful, disabling deformities. Serum alkaline phosphatase, and urinary hydroxyproline and deoxipyridinoline are elevated. Calcium and parathyroid hormone are normal. Treatment with diphosphonates, calcitonin and vitamin D has been unsuccessful. We present the surgical technology and the results to short and long term of 13 interventions on 8 patients.


CONCLUSIONS
Progressive osteoclastic reabsorption accompanied by weak osteoblastic activity results in medullary expansion characterized by rarefaction of the bone marrow, which is replaced by fibrous tissue and fat. FEO is histologically similar to Paget disease, but the age of onset, the distribution of the bone lesions, the dental and middle ear alterations, and the clinical progression are different. These features also differentiate FEO from fibrous dysplasia, fibrocystic osteitis and imperfect osteogenesis. The gene responsible for FEO is located in the 18q21-22 chromosome region. Mutations in TNFRSF11A, the gene encoding receptor activator of nuclear factor-kappa-B (RANK), has been recently identified as the cause of FEO. A duplication of 18 base pairs in exon 1 of the TNFRSF11A gene suggests that this corresponds to the site of the anomaly and can be considered a "hot spot" for mutations.
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Service d'ORL et de Chirurgie Cervico-Faciale, Hôpital Universitaire Vall d'Hebron, Barcelone, Espagne. 3809nfi@comb.es
D001284:Atrophy / Q000150:complications / Q000473:pathology / Q000601:surgery; D002352:Carrier Proteins / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D003638:Deafness / Q000150:complications / Q000473:pathology / Q000601:surgery; D003720:Densitometry; D004432:Ear, Middle / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D010015:Osteolysis, Essential / Q000150:complications / Q000235:genetics* / Q000601:surgery; D010375:Pedigree; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D014076:Tooth Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human