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A rare, genetic primary bone dysplasia of the spondylo-epi-metaphyseal dysplasia (SEMD) group characterized by progressive short-trunked dwarfism, protruding sternum, microcephaly, intellectual disability and pathognomonic radiological findings (generalized platyspondyly with double-humped end plates, irregularly ossified femoral heads, a hypoplastic odontoid, and a lace-like appearance of iliac crests)
ORPHA:239Classification level: Disorder
To date approximately 100 cases have been reported worldwide.
Clinically, Dyggve-Melchior-Clausen disease (DMC) is characterized by progressive dwarfism with short trunk, protruding sternum, rhizomelic limb shortening, postnatal microcephaly with facial dysmorphism, coarse face and intellectual disability varying from moderate to severe. Physical measurements at birth are typically normal, with patients clinically presenting with short stature within the first two years of life along with progressive appearance of the skeletal deformities of the thorax, spine, pelvis, hands and knees. Orthopedic complications usually occur during childhood almost constantly including bilateral hip subluxation, deformations of the knees, lumbar lordosis, scoliosis and thoracic kyphosis. Radiological features include progressive flattened vertebral bodies (platyspondyly) with a double-humped shape clearly visible by 3-4 years of age, misaligned spine, metaphyseal irregularities, laterally displaced capital femoral epiphyses, and small pelvis with thickened and scalloped iliac crests. This specific aspect of iliac crests becomes clearly visible around 4 years of age, broadens through adolescence and persists into adulthood. Hands are generally short and broad with irregular shape of metacarpal bones and phalanges.
The disease is caused by mutations of the DYM gene (18q21.1). The large majority of mutations identified in the gene predict a loss of function of its product. DYM is expressed in the majority of tissue and codes for dymeclin, a protein which interacts with membranes of the Golgi apparatus, and has a role in the regulation of Golgi homeostasis and membrane trafficking
Diagnosis is based on radiological evidence revealing platyspondyly with double vertebral humps, epiphyseal and metaphyseal dysplasia and scalloped iliac crests.
Differential diagnoses include Smith-McCort syndrome, which presents with the same clinical and radiological features as DMC but without intellectual deficiency, and mucopolysaccharidosis type 4 which is clinically similar but has specific radiological and enzymatic signs.
Transmission is autosomal recessive. There is a 25% risk of disease transmission where both parents are unaffected carriers.
Management and treatment
Management requires both a multidisciplinary approach and a long-term follow-up as the disease is progressive. Preventive or corrective orthopedic surgery may be an option to manage lower limb deformities. However, due to the poor quality of osseous tissue, minimal-invasive surgery such as guided growth may be preferable
The disease often progresses towards orthopedic complications which can include lumbar lordosis, thoracic kyphosis, hip luxation, deformation of the knees and spinal cord compression secondary to instability of the atlas-axis.