Table 3.
Most common skeletal dysplasia diagnoses.
| Clinical diagnosis | Associated gene | Inheritance | Distinguishing features that may be present |
|---|---|---|---|
| Achondroplasia |
FGFR3 98% with p.Gly380Arg c.1138 G>A c.1138 G>C |
AD 75%–80% are de novo |
Micromelia, macrocephaly, midface hypoplasia |
| Hypochondroplasia |
FGFR3 Most common p.Asn540Lys c.162° C>A and c.162° C>G |
AD 30% with unknown genotype |
Mild micromelia, temporal lobe seizures, learning differences |
| Pseudoachondroplasia | COMP | AD | Micromelia, normocephaly, joint pain, significant joint laxity |
| Multiple epiphyseal dysplasia (MED) |
COMP, MATN
COL9A1, COL9A2, COL9A3 DTDST (SLC26A2) CANT1 |
AD AR 15%–20% with unknown genotype |
Joint pain, especially hips |
| Spondyloepiphyseal dysplasia congenita (SEDC) and other type 2 collagenopathies | COL2A1 | AD | Short trunk, waddling gait Cleft palate club feet |
| Leri-Weill dyschondrosteosis (LWD) | SHOX | AD | Mild micromelia Mesomelia Madelung deformity |
| Diastophic dysplasia | DTDST (SLC26A2) | AR | Joint contractures, hitchhiker thumbs, club feet |
| Spondylometaphyseal dysplasia Kozlowski (SMD-K) |
TRPV4 | AD | Scoliosis Short trunk Pectus carinatum |
| Hypophosphatasia | ALPL | AR | Life limiting with small chest and respiratory failure to normal stature with increased fractures |
| X-linked hypophosphatemic rickets | PHEX | XLD | Leg bowing Metaphyseal flaring |
| Osteogenesis imperfecta | COL1A1 or COL1A2 for types I-IV | AD | Increased fractures, Blue sclerae |
AD, autosomal dominant; AR, autosomal recessive; XLD, X-linked dominant.