Familial expansile osteolysis. A new dysplasia

Abstract

We report 40 cases in one family of an autosomal dominant bone dysplasia, which, though similar in some aspects to Paget's disease, seems unique in some features and in its natural history. The disease shows both general and focal skeletal changes, the latter being mainly in the limbs with an onset from the second decade. Progressive osteoclastic resorption is accompanied by medullary expansion which leads to pain, severe deformity and a tendency to pathological fracture. The serum alkaline phosphatase and urinary hydroxyproline are variably elevated, while other biochemical indices are normal. Most patients had an associated deafness of early onset and loss of dentition. No previous description of this disease has been found in the literature.

Expansile bone lesions in a three-generation family

“…FEO is an autosomal dominant disorder characterized by expansile bone lesions, bone pain and deformity, early onset deafness, and severe dental abnormalities [Dickson et al, 1991;Osterberg et al, 1988;Wallace et al, 1989]. This family has none of these associated findings.…”

Familial Paget's Disease of Bone: Nonlinkage to the PDB1 and PDB2 Loci on Chromosomes 6p and 18q in a Large Pedigree

“…FEO has been described in a large Northern Irish pedigree. (12,13) Osteolytic lesions, which usually develop in the long bones during early adulthood, show increased osteoblast and osteoclast activity. Hughes et al (14) showed linkage between FEO and a region of chromosome 18q21.2-18q21.3 flanked by microsatellite markers D18S51 and D18S64, with no recombinants between FEO and marker D18S42.…”

Genetic aspects of the Paget’s disease of bone: concerns on the introduction of DNA‐based tests in the clinical practice. Advantages and disadvantages of its application

“…Mutations have been identified in four genes that cause PDBrelated syndromes (FEO, ESH, EOPDB and JPD) [5][6][7][8][9], but genetic factors play an important role also in the classic form of PDB. These genes are represented respectively by: TNFRSF11A, which encodes the Receptor Activator of Nuclear factor jB (RANK) for FEO, ESH and EOPDB; TNFRSF11B, which encodes osteoprotegerin (OPG) for JPD; valosin containing protein gene (VCP) which encodes p97 protein for…”