Radiological Diagnosis

Dysplasia Epiphysealis Multiplex or Multiple Epiphyseal Dysplasia Tarda

Dysplasia Epiphysealis Multiplex (DEM) (earlier synonyms: Fairbank's Disease, Ribbing's disease, Epiphyseal dysostosis, Hereditary enchondral dysostosis) is a congenital skeletal dysplasia which presents in childhood with bilaterally symmetrical short limb dwarfism with conspicuous absence of other systemic anomalies. The characteristic defect is primarily in the epiphyses, which appear irregular but lack sclerosis [1],[2],[3]. It is a rare skeletal dysplasia, which was first described by Barrington-Ward in 1912. Later, Jansen in 1934 and Fairbank in 1935 described similar cases and the nomenclature is attributed to Fairbank [4]. Clinically bilaterally symmetrical short limb dwarfism with short, stubby hands and feet, waddling gait with coxa vara, genu valgum/varum and tibiotalar slants are characteristic. Flexion deformities and early osteoarthritis are the clinical presentations in adolescents and adult patients [1],[3].

The diagnosis is mainly radiological and distinctive radiographic features have been described for this disease along with characteristic absence of biochemical abnormalities [1][2][3][4][5][6][7][8]. Similar radiographic features along with normal laboratory parameters were seen in our patient:

1. Shortening of long bones with bilaterally symmetrical epiphyseal hypoplasias and epiphyseal irregularities at shoulder, hip and knee joints [Figure - 1][Figure - 4][Figure - 5].
2. Flaring and irregularity of adjacent metaphyses [Figure - 1][Figure - 4][Figure - 5].
3. Hypoplastic femoral heads with broad femoral necks with decreased neck shaft angle (coxa vara). Irregularity of greater trochanteric apophyses and acetabular dysplasia were also seen [Figure - 4].
4. Shallow intercondylar notches at the knee joint and beaking of proximal tibial metaphyses [Figure - 5].
5. Irregular margins of carpal bones, short metacarpals and short phalanges [Figure - 2]a with irregularities in epiphyseal and nonepiphyseal ends of phalanges [Figure - 2]b.
6. Vertebral changes simulating Scheurmann's disease with irregularities of end plates and anterior wedging of vertebral bodies [Figure - 3].

The hallmark of the disease, which is fragmented appearance of epiphyses, has also been described as a "mulberry like" appearance. In addition to the above features, delayed appearance and delayed fusion of epiphyses has also been described in DEM [1],[4].

Due to the short stature and the epiphyseal abnormalities, various diseases have to be considered in the differential diagnosis of this condition both clinically as well as radiologically. Clinically, achondroplasia is the most frequent entity under consideration in a patient with short stature. However, the radiological evidence of epiphyseal abnormalities rules out achondroplasia [5]. Radiologically the condition needs to be differentiated from Mucopolysaccharidoses (MPS) since MPS also exhibits epiphyseal fragmentation and metaphyseal flaring. However, the absence of platyspondyly and of "bullet" appearance of metacarpals, rules out MPS [1],[5]. Spondyloepiphyseal dysplasia (SED) is also a radiological differential diagnosis to be considered. SED however exhibits platyspondyly with relatively normal hands and also shows clinical abnormalities such as ocular and oral defects [1,6]. The fragmentation and hypoplasia of femoral capital epiphyses requires DEM to be differentiated from Perthes disease and cretinism. Perthes disease is usually unilateral and if bilateral, the changes are asymmetrical [1]. However, unlike Perthes disease DEM is multifocal [2]. Cretinism simulates DEM with fragmented epiphyses and retarded bone age but generalized osteoporosis and coexisting wormian bones in the skull are characteristic for cretinism [1]. DEM is believed to be a tarda form of Chondrodystrophia Calcificans Congenita [3]. Chondrodystrophia Calcificans Congenita (synonyms: Chondrodysplasia punctata, dysplasia epiphysealis punctata, stippled epiphyses) is characterized by punctate calcification of unossified cartilaginous epiphyseal centers (both primary as well as secondary) and is usually fatal before the end of the first year of life [3],[4],[6],[7].

The presence of anterior vertebral beaking is classically seen only in MPS and SED. Although anterior beaking was seen in our patient, the absence of platyspondyly and presence of irregularities in the vertebral end plates (resembling Scheurmann's disease) ruled out both SED and MPS [1],[6]. Furthermore, the changes of irregularities in both epiphyseal and non epiphyseal ends of phalanges and of tibial beaking which were seen in our patient are observations favoring DEM and are not described in either MPS or in SED [1].

The pathology is mainly in the secondary ossification centers with the primary ossification centers remaining unaffected [7]. The epiphyseal chondrocytes in the involved regions exhibit paucity in numbers and loss of normal columnar arrangement with abnormal vascular invasion. The growth plates are found to have a decreased mucopolysaccharide content specifically of galactosamine. The disease is autosomal dominant in inheritance with variable penetrance although sporadic cases have been described [1],[2],[5],[6],[8]. The genetic defect has been shown by current studies to occur due to hereditary genetic mutations on three known loci. These loci include (i) oligomeric protein mutation (COMP) on chromosome 19(19p13.1) (ii) mutation of alpha 2 chain of collagen IX (chain COL9A2) on chromosome 1(1p32) (iii) rare form associated with the third chain of collagen IX (COL9A3) on chromosome 20 [1,8]. The first loci identified on chromosome 19 contain both the mutations of DEM as well as pseudoachondroplasia [1]. The prognosis in DEM is excellent with a normal life except for premature osteoarthritis and dwarfism [2]. Awareness of the disease will be useful in the differentiation of the close radiological mimickers such as SED, MPS and cretinism; all of which individually have different prognosis and require different management. The management described in the patients of DEM is corrective osteotomies for the deformities of genu valgum/varum during childhood and physiotherapy for early onset osteoarthritis in adult age.