Although most cases of spondyloepiphyseal dysplasia tarda have an X-linked recessive mode of inheritance, both autosomal dominant and autosomal recessive forms are also known. This has been mapped to the SEDL gene in the Xp22 chromosome affecting the protein sedlin, which plays an important role in endoplasmic reticulum/Golgi vesicular transport.

Clinical Manifestations. Growth failure does not become evident until 5 to 10 years of age. The height reduction, which is primarily due to trunk shortening, becomes quite obvious by adolescence. At this time, patients complain of pain and stiffness in the back or hips. Secondary osteoarthritis of the hip is common and may become disabling. The chest is broad or barrel shaped. Adult height ranges from 52 to 61 inches.

Radiographic Findings. The distinctive configuration of the vertebral bodies is most evident in the adult lumbar spine. Initially, the vertebral bodies are mildly flattened (platyspondyly) with a hump-shaped accumulation of bone in the posterior and central portions of the cartilage ring apophysis; the disc space appears narrowed. The thoracic cage is broad, while the pelvis is small and deep. The epiphyses of the long bones show variable dysplastic changes, and osteoarthritis of the hips is evident.

SPONDYLOEPIPHYSEAL DYSPLASIA CONGENITA

Spondyloepiphyseal dysplasia congenita is the more severe form affecting the spine and epiphyses of long bones. Most cases of spondyloepiphyseal dysplasia congenita are a result of spontaneous mutation. This type of short-trunk dwarfism is typically transmitted as an autosomal dominant trait, although cases of autosomal recessive inheritance are known. Mutations to COL2A1 locus on chromosome 12 lead to abnormal type II collagen.

Clinical Manifestations. In the newborn, a broad or barrel chest, deep Harrison’s grooves, and pigeon chest suggest the diagnosis. Flat, dishlike facies, cleft palate, and wide-set eyes are other early signs. In older children, the short neck makes the normal-sized head appear to rest directly on the shoulders. Myopia and retinal detachment or degeneration is occasionally seen.

The limbs show mild rhizomelic shortening but are long in comparison with the trunk; the hands and feet are essentially normal. Ligamentous laxity is excessive. Marked lumbar lordosis and moderate kyphoscoliosis occur in late childhood or early adulthood. Adults reach a height of only 33 to 52 inches.

Motor development is often delayed. In 50% of patients, hypotonia, ligamentous laxity, and odontoid hypoplasia result in atlantoaxial instability leading to spinal cord compression, which first manifests as overwhelming fatigue and decreased endurance.

Radiographic Findings. Retarded ossification of the pubic bones, femoral heads, and epiphyses of the knees, calcanei, and tali is the major feature in young children. Early in life, the vertebral bodies are ovoid or pear shaped but become flattened and irregular with time, resulting in kyphoscoliosis. Careful radiographic evaluation of the cervical spine is important because of the hazards associated with odontoid hypoplasia. Coxa vara is common, and rhizomelic shortening of the long bones with minimal dysplastic changes in the hands and feet may also be seen.