76 Osteopetrosis, Adult Type
Osteopetrosis, Adult Type 807
Juvenile osteopetrosis, osteopetrosis with late manifestation, benign osteopetrosis types I, II and III included
Often asymptomatic, skull sclerosis, pathologic frac- tures, dental abscesses, cranial nerve compromise Frequency: 1 in 20,000 births; 1 in 100,000 in Brazil.
Genetics
Autosomal dominant osteopetrosis type II (OMIM 166600) can result from dominant negative mutations in the CLCN7 chloride channel gene at 16p13; loss-of- function mutation in the same gene causes autosomal recessive osteopetrosis in the homozygous state; auto- somal recessive intermediate type (OMIM 259710)
Clinical Features
• Often asymptomatic, diagnosis from incidental X-ray findings
• Dental abscess, osteomyelitis of the mandible (10–30%)
• Chronic rhinitis
• Visual and hearing impairment, facial palsy
• Hepatosplenomegaly
• Bone pain (lumbar spine)
• Increased bone fragility
• Type I: Pronounced osteosclerosis of the cranial vault, variable sclerosis of vertebrae, few fractures
• Type II: Sclerosis of skull base; end-plate thicken- ing of vertebrae (‘rugger-jersey spine’) and of bones in the pelvis; increased frequency of frac- tures; increased levels of serum acid phosphatase
• Type III: milder phenotype; mild generalized in- crease in bone density, modeling defects of distal femurs, coxa vara, no evidence of cranial nerve encroachment
Differential Diagnosis
• Other conditions causing increased bone density
• Other osteopetroses
Radiographic Features Skull
• Sclerosis and thickening of the calvarium (type I)
• Sclerosis of skull base (type II)
• Narrowing of neural and vascular foramina
• Intracranial calcifications (basal ganglia)
• Short mandibular body
Generalized Bone Defects
• Varying degrees of symmetrical, uniform increase in skeletal density, with loss of normal trabecular structure
• Splayed metaphyses
• Evidence of intermittent activity of the sclerosing process, with alternating transverse bands of radiolucency and sclerosis in metaphysis of long bones and arcuate bands paralleling iliac crests (type II)
• Multiple fractures (type II)
• Osteomyelitis, especially of mandible
• Delayed skeletal maturation Spine
• ’Sandwich’ vertebrae (dense end-plates, normal density centrally); bone-in-bone appearance (type II)
• Spondylolysis and spondylolisthesis Chest
• Homogeneously dense ribs and clavicles
• Flared ribs
Bibliography
Andersen PE, Bollerslev J. Heterogeneity of autosomal domi- nant osteopetrosis. Radiology 1987; 164: 223–5
Bollerslev J, Mosekilde L. Autosomal dominant osteopetrosis.
Clin Orthop Relat Res 1992; 294: 45–51
Johnston CC, Lavy N, Lord T, Vellios F, Merritt AD, Deiss WP.
Osteopetrosis: a clinical, genetic, metabolic, and morpho- logic study of the dominantly inherited, benign form. Med- icine 1968; 47: 149–67
Takacs I, Cooper H, Weaver DD, Econs MJ. Bone mineral densi- ty and laboratory evaluation of a type II autosomal domi- nant osteopetrosis carrier. Am J Med Genet 1999; 85: 9–12 Walpole IR, Nicoll A, Goldblatt J. Autosomal dominant osteo-
petrosis type II with “malignant” presentation: further sup-
port for heterogeneity? Clin Genet 1990; 38: 257–63 O
Osteopetrosis, Adult Type 808
Fig. 76.1. aPatient 1, age 10 years; b patient 2, age 60 years. Note thickening and sclerosis of calvarium and, to a greater extent, of skull base. In a maxillary and facial bones are also densely sclerotic and paranasal sinuses are obliterated
a b
a b
c
Fig. 76.2 a–c. Patient 2, age 60 years.
Vertebrae show dense end-plates and a normal density centrally, giving rise to characteristic ‘sandwich’ appearance of the vertebral bodies. Note spondylolysis and spondylolisthesis in lumbar spine (c)
Osteopetrosis, Adult Type 809
O
Fig. 76.3. Patient 2, age 60 years.
Sclerosing process involves most pelvic bones (areas spared include central portions of iliac wings and part of ischial bones), sacrum, and proximal femurs. Note arcuate bands of decreased density paral- leling iliac crests
Fig. 76. 4. aPatient 2, age 60 years;
b, c patient 3, age 14 years. Vary- ing degrees of bone sclerosis.
Medullary cavity is still dis- cernible within markedly thick- ened cortices (a)
a
b
c
Osteopetrosis, Adult Type 810
Fig. 76.6 a, b.
Patient 5, age 7 years. This case illustrates the possible occurrence of ‘intermediate’ forms of osteo- petrosis characterized by disease onset in childhood, absent or mild symptoms, and benign clinical course. Radiographic manifesta- tions include sclerosis with striking metaphyseal modeling defects, and alternating bands of increased and normal density in distal femurs and finger phalanges
a b
Fig. 76.5.
Patient 4, age 15 years.
Note diffuse, homo- geneous sclerosis of tarsals and tubular bones
