Multipele epifysaire dysplasie: Een skeletaandoening met een neuromusculaire presentatie

Introduction: Multiple epiphyseal dysplasia (MED) is a clinically and genetically heterogenous skeletal dysplasia. Thus far, five different genes are known to be involved in autosomal dominant MED: the COMP and MATN3 genes and the genes coding for the α1, α2, and α3 chains of collagen IX (COL9A1, COL9A2, and COL9A3). A quarter of the patients with MED has a recessive form. Common clinical features are: short stature, short limbs, joint stiffness and pain. During childhood, MED can also present with predominant neuromuscular features like hypotonia and muscle weakness. Here we describe a patient with MED who was initially thought to have a neuromuscular disorder. Case description: Patient A, a 7-year-old boy had difficulties with walking, running, and jumping for three years. When climbing stairs, he had to pull himself up with his arms. On examination his body height was -1,5 SD below the mean. He had broad hands and feet, a brachydactyly and a lumbar hyperlordosis. Muscle weakness of the upper legs was present, leading to a waddling gait. Laboratory investigations (serum creatine kinase) and muscle biopsy did not show any abnormalities. Because of his stature a skeletal dysplasia was considered. The diagnosis MED was confirmed by radiological investigations and molecular analyses. A pathogenic mutation in the COMP gene was found. Conclusion: During childhood, MED can present with neuromuscular features like exercise intolerance, hypotonia and a mild, predominantly proximal muscle weakness. The presence of specific clinical and radiological skeletal symptoms and signs can point to the correct diagnosis, which can be confirmed by mutation analysis of the involved genes.