IllnessChondrodysplasia, metaphyseal; differential diagnosis

NGS +

Metaphyseal chondrodysplasia is a heterogeneous group of congenital disorders caused by various mutations that result in alterations of the long tubular bones with normal epiphyses. Patients present with short limbed short stature with genu varum, coxa vara and spinal abnormalities. Three main subtypes are distinguished: type Murk Jansen is the most severe form, while type Schmid is less severe (often confused with rickets). The McKusick type is most common in Amish and Finnish populations. Type Murk-Jansen is associated with mental retardation and marked short stature. Type Schmid is often diagnosed at an older age because of the pronounced coxa vara and genu varum, and it is characterized by short-limbed short stature, affecting mainly the proximal femur and increasing lumbar lordosis. The McKusick type is often associated with atlanto-axial instability due to odontoid hypoplasia, ankle deformity (due to particularly severe fibula growth), impaired immunocompetence, increased risks for malignancy, intestinal malabsorption and megacolon. Autosomal dominant and recessive inheritance patterns are common. Because the molecular genetic yield for skeletal dysplasias generally hardly exceeds 50-60%, a negative DNA test result does not exclude the clinical diagnosis.

References: https://www.ncbi.nlm.nih.gov/books/NBK547823/

https://www.ncbi.nlm.nih.gov/books/NBK84550/

https://www.ncbi.nlm.nih.gov/books/NBK1477/

• Alias: Chondrodysplasie, metaphysäre, AR
• Alias: McKusick-Chondrodysplasie
• Allelic: Aplastic anemia, susceptibility to (SBDS)
• Anauxetic dysplasia 1 (RMRP)
• Cartilage-hair hypoplasia (RMRP)
• Chondrodysplasia, Blomstrand type (PTH1R)
• Cleidocranial dysplasia (RUNX2)
• Cleidocranial dysplasia, forme fruste, dental anomalies only (RUNX2)
• Cleidocranial dysplasia, forme fruste, with brachydactyly (RUNX2)
• Eiken syndrome (PTH1R)
• Failure of tooth eruption, primary (PTH1R)
• Metaphyseal anadysplasia 1 (MMP13)
• Metaphyseal anadysplasia 2 (MMP9)
• Metaphyseal chondrodysplasia, Murk Jansen type (PTH1R)
• Metaphyseal chondrodysplasia, Schmid type (COL10A1)
• Metaphyseal dysplasia with maxillary hypoplasia +/- brachydactyly (RUNX2)
• Metaphyseal dysplasia without hypotrichosis (RMRP)
• Metaphyseal dysplasia, Spahr type (MMP13)
• Shwachman-Diamond syndrome 1 (SBDS)
• Shwachman-Diamond syndrome 2 (EFL1)
• Spondyloepimetaphyseal dysplasia, Missouri type (MMP13)