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Spondylo-epi-metaphyseal dysplasia (SEMD) matrilin 3 type: homozygote matrilin 3 mutation in a novel form of SEMD
  1. Z U Borochowitz1,*,
  2. D Scheffer2,*,
  3. V Adir1,
  4. N Dagoneau2,
  5. A Munnich2,
  6. V Cormier-Daire2
  1. 1The Simon Winter Institute for Human Genetics, Bnai-Zion Medical Center, Rappaport - Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
  2. 2Department of Medical Genetics and INSERM U393, Hôpital Necker Enfants Malades, Paris, France
  1. Correspondence to:
 Zvi U Borochowitz, MD
 The Simon Winter Institute for Human Genetics, Bnai-Zion Medical Center, PO Box 4940, Haifa, 31048, Israel;

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Osteochondrodysplasia is a heterogeneous group of conditions caused by impaired development of osseous skeleton. Within this group, spondylo-epi-metaphyseal dysplasia (SEMD) represents a subgroup which includes a number of conditions associated with vertebral, epiphyseal, and metaphyseal anomalies. The International Classification recognises at least 15 distinct entities within this group as defined by a combination of clinical, radiological, and molecular data.1 Mutations in the genes encoding structural proteins of the cartilage extracellular matrix (that is, cartilage oligomeric matrix protein, type II collagen, perlecan) or involved in posttranslational processing and transport (lysosomal storage disorders, sulfation protein (PAPSS2), regulator of chromatin (SMARCAL1), transcription initiation factor kinase (EIFKA3)) have been previously shown to be responsible for different forms of SEMD.1–6 However, a large number of SEMD conditions are still defined on purely descriptive features. Here, we describe five patients from a large consanguineous family of Arabic-Muslim origin with short-limb dwarfism with distinct skeletal dysplasia which, to our knowledge, has not been described previously. The manifestations and a constellation of radiographic bony abnormalities are unique in this entity. As there are abnormalities in the vertebral bodies, long bones, and specifically the lower limbs involving epiphyses and metaphyses, we suggest that this entity be called spondylo-epi-metaphyseal dysplasia, bowed-legs type. This hitherto unreported form of autosomal recessive SEMD is caused by homozygous mutation in matrilin 3 (MATN3), a component of the extracellular matrix of cartilage. This finding not only provides a molecular explanation for a novel form of SEMD but also expands the phenotype range of MATN3 defects which have been previously identified in autosomal dominant epiphyseal dysplasia and idiopathic hand osteoarthritis.7,8


In this family, five affected individuals were found to have disproportionate dwarfism with similar clinical and radiological features. Patient 1 (figs 1 and 2) was born to healthy parents of Arabic-Muslim …

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  • * These authors equally contributed to this work.

  • Conflicts of interest: none declared.