Spondyloepiphyseal dysplasia with congenital joint dislocations is characterized by joint dislocations commonly in knee, elbow and hips with wide metaphyses, epiphyseal changes and vertebral changes such as platyspondyly, end plate irregularities. Joint dislocations, especially of knees may be congenital. Talipo equinovarus deformities also may be present at birth. Short stature is noted between 2 to 5 years, but length less than 2 SD below normal during infancy is reported. Barrel chest and genu valgum are common. Depression of inferior part of sternum, flat and broad feet, rhizomelia and brachydactyly type E are seen in some cases. Height is usually between -4SD to – 6SD, but cases with marked short stature with height upto -8 SD have been reported. Development of kyphoscoliosis also contributes to the short stature.
Increasing interpedicular distance from T12 to L1/2 is characteristic and differentiates from other spondyloepiphyseal dysplasias. Development of kyphoscoliosis is common and may mask the characteristic abnormality of interpeduncular distance. The intervertebral distance is reduced with end plate irregularities are seen. Coronal clefts may be observed in young children. Epiphyseal abnormalities include extra epiphyses of carpals, advanced bone age, small epiphyses of hips and metacarpals. Epiphyses of lower ends of femoral bones are hypertrophies and seen to take triangular or rectangular shapes. Joint dislocations of hips, knees and elbows are common. Fetuses were prenatally diagnosed because of ultrasonographic diagnosis of genu recurvatum.
Extraskeletal manifestations such as cardiac involvement and hearing loss may be present. In a large family with CHST3-related SED mild to severe deafness of mixed type was reported. Cardiac abnormalities are mainly valvular involvements but ventricular septal defect is also reported. Any or many of mitral, tricuspid, aortic and pulmonary valves can be involved. Heart defects may be underreported as many patients were not screened by echocardiography.
Fifty nine patients with this disorder have been reported worldwide. Presence of normal face distinguishes this disorder from Larsen syndrome which is a common cause of congenital joint dislocations. Other features suggesting the diagnosis of Larsen syndrome is spatulate fingers which usually are not seen in CHST3-related SED though broad thumbs and great toes are noted in some cases.
The disorder has an autosomal recessive inheritance. Being very rare, many families with this disorder are consanguineous. Large families with pseudodominance due to consanguinity over generations have been reported.
CHST3