Abstract
Spondyloepiphyseal dysplasia congenita (SEDC) is the most common of the spondyloepiphyseal dysplasia and often presents in the prenatal period. SEDC is an autosomal dominant disorder that results from mutations in type II collagen encoded by the gene COL2A1 . Ultrasound findings include delayed ossification of the epiphyses of the long bones. The femora may appear to have an absent femoral neck. The femora and humeri can appear bowed, and the long bones of the arms and legs grow but usually measure below the 5th percentile. Sonolucency secondary to delayed ossification of the vertebral bodies may be seen, and vertebral bodies often appear flattened or small. Pierre Robin sequence and club feet can also occur.
Keywords
SEDC, spondyloepiphyseal dysplasia congenita, type II collagen, ossification delay
Introduction
Spondyloepiphyseal dysplasias are rare, nonlethal disorders of bone growth. These disorders primarily affect the spine (spondylo-) and the ends of the long bones (epiphyseal), resulting in a short-trunk dwarfism. These disorders are clinically and genetically heterogeneous. Some spondyloepiphyseal dysplasias manifest in the prenatal period, including spondyloepiphyseal dysplasia congenita (SEDC), whereas others manifest in childhood. Other spondyloepiphyseal dysplasias are diagnosed in later life as early-onset arthropathy. This chapter focuses on the most common form that is prenatal in onset, SEDC, which results from mutations in type II collagen encoded by COL2A1 .
Disorder
Definition
SEDC is a nonlethal disorder caused by mutations in the gene that encodes type II collagen, COL2A1 . Abnormal synthesis of type II collagen, a major component of cartilage, leads to short stature, kyphoscoliosis, early-onset osteoarthritis, and hearing and vision problems.
Prevalence and Epidemiology
The exact prevalence is unknown but is one of the more common nonlethal skeletal disorders.
Etiology, Pathophysiology, and Embryology
Autosomal dominantly inherited mutations in COLA2A1, the gene that encodes for the type II collagen protein, are responsible for SEDC, and therefore both sexes are equally affected. If both parents are affected because of nonassorting mating, there is a 25% chance of homozygosity, which is generally lethal in infancy.
Type II collagen is highly expressed in certain tissues, in particular in cartilage and the vitreous of the eye, and thus affected individuals have both short stature and a high incidence of eye abnormalities. Other rare forms of spondyloepiphyseal dysplasias are inherited as autosomal recessive and X-linked disorders (spondyloepiphyseal dysplasia tarda).
Manifestations of Disease
Clinical Presentation
Patients with SEDC often have odontoid hypoplasia, kyphoscoliosis, and early-onset hip and knee joint degeneration, leading to significant orthopedic complications. There is an increased incidence of cleft palate without cleft lip and micrognathia (Pierre Robin sequence) ( Chapter 137 ).
Lumbar lordosis, thoracic scoliosis, and kyphoscoliosis are usually not evident at birth but may develop in childhood. These abnormalities in spinal curvature tend to progress, and severe kyphoscoliosis can lead to difficulties in pulmonary function, restrictive lung disease, and ultimately cor pulmonale.
In SEDC, the neck is short, and atlanto-axial instability secondary to odontoid hypoplasia leads to increased risk of spinal cord compression particularly on neck flexion or extension. Other skeletal abnormalities that are often seen include flattened vertebrae (platyspondyly), pectus carinatum with barrel-shaped chest, and abnormally formed hip joints with coxa varus leading to abnormal hip articulation, frequently leading to gait abnormalities. Early-onset arthritis and decreased joint mobility are also frequently observed, particularly at the hip and the knee.
The most common ocular abnormalities are severe myopia, vitreous degeneration, and retinal detachment. About 25% of individuals have severe hearing loss or deafness. Adult height ranges from 3 to 4 feet tall. Intelligence is not affected.
Imaging Technique and Findings
Ultrasound.
Prenatal diagnosis may also be suggested by ultrasound (US) findings of delayed ossification of the pubis and epiphysis of the femur and humerus, flattened vertebra and narrow intervertebral disk space ( Figs. 56.1 and 56.2 ), and flattened facies with micrognathia ( Fig. 56.3 ). US findings include delayed ossification of the epiphyses of the long bones. Delayed epiphyseal endochondral ossification can also be seen, for example, in the chest with delay of ossification of the sternal centers ( Fig. 56.4 ). The long bones of the arms and legs grow but measure below the fifth percentile. Sonolucency secondary to delayed ossification of the vertebral bodies may be seen, and vertebral bodies may appear flattened or small. Bowing of the femur and humerus may also be present, though this is less common. Head size is normal. Clubfoot and cleft palate present with the previously mentioned findings are suspicious for SEDC.
