Clinical and radiographic findings in multiple epiphyseal dysplasia caused by MATN3 mutations: Description of 12 patients

Abstract

Multiple epiphyseal dysplasia (MED) is characterized by pain and stiffness in joints and delayed and irregular ossification of epiphyses. Causative mutations have been recognized in six different genes. We have identified disease-causing mutations in the gene encoding matrilin-3, an extracellular matrix protein, in seven families with autosomal dominant MED. Review of the clinical and radiographic features in 12 of the affected family members shows a uniform pattern of skeletal anomalies in all patients with considerable degree of variability in severity, both between and within families. The characteristic clinical findings are onset of symptoms in early childhood with predominance of knee and hip related complaints, normal stature, and early-onset osteoarthritis. Radiographs show small and irregular epiphyses and mild metaphyseal irregularities and striations, especially at the knees and hips and mild spinal changes. Despite overlap, both clinically and radiographically, with other forms of MED, the described features may help to differentiate this particular form from other entities within the MED spectrum.

Mutations in the known genes are not the major cause of MED; distinctive phenotypic entities among patients with no identified mutations

“…Taking together with the previously reported mutations, 10,14,15,18,19 Figure 5 Patient 16 was diagnosed with MED in early childhood. At 10 years he was asymptomatic but had genua vara, increased lumbar lordosis, short stature (o3%) and generalized joint laxity.…”

“…10,19 As five additional patients had been ascertained since the initial analysis, MATN3 exon 2 was amplified from their samples as previously described 10 and analysed for sequence variations by CSGE and sequencing. …”

“…The patients with mutations in the COMP, MATN3 and DTDST genes presented with clinical and radiographic findings that are well in accordance with the phenotypes previously reported in the presence of similar mutations. Patients with MATN3 mutations present with features partially overlapping with MED caused by COMP and collagen IX mutations, 19 but may be differentiated from these by a careful assessment of their skeletal radiographs. As in the other forms of MED, 6,15 however, there may exist a 'window of opportunity' in mid-childhood for differentiating these forms from each other, since the radiographic findings become less characteristic towards closure of the growth plates.…”

Sık görülen iskelet diplazileri ve hareket analizi özellikleri

“…Her ne kadar mutasyonlar birçok hastada 19. kromozomda yeralan COMP matriks glikoproteinini kodlayan genden kaynaklansa da, Tip 9 kollajende yer alan alfa 2 liflerinin yapısal bozukluğu, matrilin-3 defekti ve transport protein mutasyonlarının da etken olabileceği gösteril-miştir. [1,[15][16][17] Şekil 12. Multipl epifizyel displazili bir olguda solda daha belirgin olmak üzere diz valgus deformitesi.…”

Early Osteoarthritis and Double-Layered Patella in a Patient With Multiple Epiphyseal Dysplasia

“…Since it can present mildly, proper diagnosis can be difficult. 5 It is a genetically heterogeneous disease and its exact mechanism is not clearly known. However, some causative genes resulting in maturational delay in the epiphysis of the bone have been previously reported.…”