Type II autosomal dominant osteopetrosis (Albers-Schönberg disease): clinical and radiological manifestations in 42 patients

doi:10.1016/S8756-3282(99)00244-6

Bone

Volume 26, Issue 1, January 2000, Pages 87-93

https://doi.org/10.1016/S8756-3282(99)00244-6 Get rights and content

Abstract

Type II autosomal dominant osteopetrosis (ADO II, Albers-Schönberg disease) is a genetic condition characterized by generalized osteosclerosis predominating in some skeletal sites such as the spine and pelvis. ADO II is rare, and most available clinical descriptions are based on small numbers of patients. We report the clinical and radiological manifestations in 42 ADO II patients. To our knowledge, this is the largest series reported so far. Our inclusion criterion was presence on radiographs of the spine of vertebral endplate thickening, producing the classic sandwich vertebra appearance. We found various patterns of sandwich vertebra, of which we provide a description to assist physicians in diagnosing ADO II. The classic bone-within-bone appearance was present in most but not all skeletal sites. The radiological penetrance of the disease was high (90%) and increased after 20 years of age. As many as 81% of our patients experienced clinical manifestations. Fractures were common (78% of patients) and healed slowly. Hip osteoarthritis developed in 27% of patients and required arthroplasty in 9 of the 16 affected hips. Nonmandibular osteomyelitis occurred in 4 cases (11%). Twenty-four percent of patients had thoracic or lumbar scoliosis. Orthopedic surgery was performed in 52.8% of patients, of whom half had at least three surgical procedures for internal fracture fixation, arthroplasty, limb deformity correction, or treatment of surgical complications. There was a high rate of surgical complications including nonunion, infection, prosthesis loosening, and intraoperative fractures. Nearly two-thirds of patients (64%) had stomatologic manifestations, including mandibular osteomyelitis in 4 patients (11%). Cranial nerve involvement responsible for hearing loss, bilateral optic atrophy, and/or facial palsy was present in 14 patients but was clearly attributable to ADO II in only 6 cases (16%). This large series sheds new light on several aspects of ADO II, most notably the possibility of severe clinical complications. Although other forms of osteopetrosis are considerably more severe, the name “benign osteopetrosis” previously used for ADO II is probably a misnomer.

Introduction

At least 20 different types of osteopetrosis have been described in animals and humans.16 Their common denominator is a universal osteosclerosis. Most result from a resorption defect, whose molecular cause has been identified in some cases. Type II autosomal dominant osteopetrosis (ADO II) is characterized primarily by radiographic vertebral endplate thickening producing the classic sandwich vertebra appearance. During the 1980s, Bollerslev et al. delineated the clinical, radiological, and laboratory manifestations of ADO II in 13 patients belonging to two different families.3

The prevalence of ADO II has been estimated at 0.2/100,000 in Brazil and 5.5/100,000 in Denmark.4, 15 ADO II is transmitted on an autosomal dominant basis.12 Clinical manifestations include cranial nerve palsy, mandibular osteomyelitis, and multiple fractures contrasting with the increase bone density.5, 6, 12, 16 ADO II manifests radiologically as diffuse osteosclerosis most prominent in the vertebral endplates (sandwich vertebra), iliac wings (bone-within-bone appearance), and skull base.1, 8

Recently, ADO II was localized to chromosomal region 1p21 by a targeted linkage analysis performed on a large Danish family.19 To conduct a genetic study that aims to determine this localization precisely, we sought to identify most of the cases of ADO II in France. Herein, we report the clinical and radiological features in the 42 cases of ADO II identified thus far. This is the largest series reported to date.

Section snippets

Recruitment

A standardized questionnaire was sent to 750 French hospital physicians (rheumatologists, radiologists, orthopedic surgeons, and geneticists) asking whether they had seen patients with any form of dominant osteopetrosis. These patients were then investigated by the authors. The study was conducted in accordance with the Declaration of Helsinki.

Criteria for ADO II

The inclusion criterion was presence of the sandwich vertebra appearance (see Figure 3, Figure 4, Figure 5). Exclusion criteria used to rule out other

Patients and families

Among the 42 cases included in our study, 29 were familial, from 10 different families, and 13 were apparently sporadic. Mean age was 39.5 years (range 7 to 71 years), and the male-to-female ratio was 22:20. Adults ranged in height from 150 to 180 cm (mean 164.6 cm).

The dominant pattern of transmission of ADO II is illustrated by the pedigree of the largest family, shown in Figure 1. Penetrance estimated using method 1 was 90% (95% confidence interval [CI], 80.5% to 99.5%). There was only one

Discussion

This large series of ADO II highlights the marked penetrance and high complication rate of the disease. It also clarifies a number of radiological features of potential diagnostic usefulness and provides information on the frequency and pattern of manifestations in sporadic cases. Previous large series of ADO II include a report by El Tawil et al. of the radiological features in 42 ADO patients including 29 type II patients8 and a description by Bollerslev et al. of the clinical, radiological,

Acknowledgements

This work was supported by the “Société Française de Rhumatologie” and by the “Fonds d’Etude et de Recherche du Corps Médical des Hôpitaux de Paris.” The authors thank the 70 doctors who provided data and especially Dr. Maroteaux and Dr. Le Merrer from Necker’s Hospital (Paris).

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There are more references available in the full text version of this article.

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Original ArticlesType II autosomal dominant osteopetrosis (Albers-Schönberg disease): clinical and radiological manifestations in 42 patients

Abstract

Introduction

Section snippets

Recruitment

Criteria for ADO II

Patients and families

Discussion

Acknowledgements

Am J Hum Genet

Heterogeneity of autosomal dominant osteopetrosis

Radiology

Albers Schönberg Disease results from a transient infantile bone resorption deficit (Abstract)

J Bone Miner Res

Autosomal dominant osteopetrosisbone metabolism and epidemiological, clinical, and hormonal aspects

Endocr Rev

Osteopetrosis. A genetic and epidemiological study

Clin Genet

Fracture patterns in two types of autosomal-dominant osteopetrosis

Acta Orthop Scand

Autosomal dominant osteopetrosisan otoneurological investigation of the two radiological types

Laryngoscope

Intramedullary fixation of fractures of the femur in a case of osteopetrosis

J Bone Joint Surg

Benign osteopetrosisa review of 42 cases showing two different patterns

Skeletal Radiol

Original Articles
Type II autosomal dominant osteopetrosis (Albers-Schönberg disease): clinical and radiological manifestations in 42 patients