64 Multiple Epiphyseal Dysplasia
MED, EDM 1, Fairbank disease, Ribbing disease, dysostosis epiphysealis multiplex
Moderately short stature, brachydactyly, waddling gait, prominent joints with restricted mobility Frequency: Undetermined; male-to-female ratio 3:1.
Genetics
Autosomal dominant (OMIM 132400); genetically heterogeneous; EDM 1 results from mutation of the cartilage oligomeric matrix protein (COMP) mapped to 19p13.1, allelic to pseudoachondroplasia; EDM 2, characterized by pain in ankle and knee, slightly short hands, prominent joints, no spine and chest ab- normalities due to mutation of COL9A2 gene, mapped to 1p32.2-p33; EDM 3 due to mutation in the COL9A3 gene, maps to 20q13.3; autosomal recessive EDM 4, which can be caused by mutation in the DTDST gene on 5q32-q33.1, characterized by flat femoral head, lack of metaphyseal irregularities in the metacarpals and phalanges; autosomal dominant EDM 5, characterized by easy fatigue and joint pain at knees and hips, normal stature and osteoarthrosis in early adulthood, due to mutations in the matrilin-3 (MATN3) gene at 2p23-p24.
Clinical Features
• Moderate short limb dwarfism (stature close to 150 cm in the adult) identifiable during childhood, normal body proportions
• Normal head and facies
• Hip dysplasia and degenerative arthritis
• Abnormal and/or painful gait
• Articular limitations, often painful
• Short hands and feet, finger hyperextensibility
• Thoracic kyphosis, back pain
Differential Diagnosis
• Other multiple epiphyseal dysplasias
• Jouberg-Holt syndrome
• EDM with myopia and deafness
• Mild form of pseudoachondroplasia
• Spondyloepimetaphyseal dysplasia, Irapa type
Radiographic Features Extremities
• Epiphyseal dysplasia (irregularity, fragmentation, flattening, smallness), most prominent at hips, knees, ankles, wrist, and hands
• Early osteoarthritis, reduced joint spaces
• Short femoral neck
• Varus/valgus deformity of knee
• Sloping end of distal tibia Hands
• Short and broad tubular bones, with metaphyseal flaring
• Short middle and distal phalanges, short meta- carpals with proximal pseudoepiphyses
• Cone-cup epiphyses-metaphyses
• Irregular carpal bones, delayed carpal ossification
• Advanced bone age in unaffected epiphyses Spine
• Ovoid vertebral bodies (childhood)
• Varying degrees of vertebral flattening (usually mild)
• End-plate irregularities (thoracic spine)
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Bibliography Makitie O, Mortier GR, Czarny-Ratajczak M, Wright MJ, Suri M, Rogala P, Freund M, Jackson GC, Jakkula E, Ala-Kokko L,
Fig. 64.2.
Patient 2, age 17 years. There are minimal end-plate irregu- larities in the lower thoracic spine. Vertebrae are otherwise normal
Fig. 64.1. Patient 1, age 8 years, compared with unaffected 10-year-old brother. Proportionate short stature, normal head and facies, articular limitation, and short hands and feet.
(Reprinted, with permission, from Caterini et al. 1996)
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Fig. 64.3. aPatient 3, age 3 years and 6 months. Note small, irregu- lar capital femoral epiphyses, with fragmentation and sclerotic changes on the right. Acetabular angles are increased, and acetabu- lar roofs are underdeveloped.
Multiple epiphyseal dysplasia pa- tients with small epiphyses are traditionally classified as having the more severe ‘Fairbank type’ of the disease. However, this classifi- cation is often impossible, as it is in this patient, owing to coexis- tence in the same individual of more severe and milder changes in different sites. b Patient 2, age 17 years. The femoral heads are flat and deformed, with cystic de- generation on the left side. The ac- etabular roofs are irregular. Pa- tients with flat, instead of small, epiphyses are traditionally classi- fied as having the mild ‘Ribbing type’ of the disease. However, a dissociation is frequently ob- served in the degree of severity of epiphyseal involvement from one site to another
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b
Fig. 64.4. a Patient 3, age 3 years and 6 months: mild epiphyseal irregularities. b Patient 2, age 17 years: more severe epiphyseal irregularities and flattening
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Fig. 64.5. aPatient 3, age 3 years and 6 months. Note mild shorten- ing of the tubular bones, distal pseudoepiphyses of the 1st meta- carpal, and bone age retarda- tion (bone age corresponding to 2 years and 8 months). b Patient 2, age 17 years. Note mild changes in hands, with flattened, partially sclerotic epiphyses, and bone age retardation (bone age correspon- ding to 14 years)
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