Spondyloepiphyseal Dysplasia Clinical Presentation

Updated: Nov 02, 2015
  • Author: Shital Parikh, MD; Chief Editor: Dennis P Grogan, MD  more...
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SED congenita

Wynne-Davies and Hall identified 2 clinical groups of SED congenita, differentiated by the magnitude of skeletal involvement and severity of coxa vara of the hip. [12] This distinction can be made in patients aged 3-4 years. Patients with mild coxa vara fall just below the third percentile of height. Those with severe coxa vara have adult height of 90-120 cm. The hands and feet are normal in length, in striking contrast to the proximal (rhizomelia) and middle segments (mesomelia) of the limbs, which are extremely short.

Cervical myelopathy may result from atlantoaxial instability. Symptoms include delayed motor development, decreased endurance, progressive weakness, hypotonia, sleep apnea, and alterations in respiration. Respiratory insufficiency may develop secondary to thoracic dysplasia. Sensations tend to be maintained for a considerable period. Neurologic findings are often greater on one side than the other because the cervical cord often is displaced to one side. Some children may have a triad of findings including odontoid hypoplasia, atlantoaxial instability, and spinal cord compression; symptoms often begin when they are aged 5-10 years. Gait problems are often attributed to the hip and knee deformities, and the diagnosis of the cervical deformities may be delayed. Cervical kyphosis may be present in some patients.

Spinal deformities, such as thoracolumbar scoliosis, kyphosis, and kyphoscoliosis, are common in these patients. These deformities occur much earlier, progress more quickly, and are more rigid than those in idiopathic conditions. Spinal cord compression and spastic paraparesis can occur, primarily with kyphosis or kyphoscoliosis.

Patients with hip deformities (coxa vara, avascular necrosis like changes in capital femoral epiphysis) may present with hip pain or decreased walking tolerance. They are prone to premature osteoarthritis. Some patients may have valgus deformities of the knee in addition to coxa vara of the hip. These patients frequently have knee pain and increased laxity of medial collateral ligament. Some patients have clubfeet. [13, 14]

SED tarda

Children with SED tarda appear normal at birth and develop clinical manifestations of trunk or hip when older than 4 years. Some patients experience mild growth retardation in childhood. Mild disproportionate trunk shortening occurs, but many patients achieve an adult height of more than 153 cm. Thus, true dwarfism may not be present.

Atlantoaxial instability may be present, and patients may present with neurologic deficits or symptoms. Scoliosis or thoracic kyphosis with exaggerated lumbar lordosis may develop. Patients may present with back pain or stiffness. [15]

Patients may present with hip pain and stiffness in the first or second decade of life. Progressive symptomatic osteoarthritis of the hips and knees may be seen. Angular deformities of the lower extremities are mild.



SED congenita

The diagnosis can be made at birth. Newborn infants are short, with disproportionate involvement of the trunk. In certain cases, patients who are assessed in the neonatal period and in their first year of life may not demonstrate short stature based on clinical height measurements and reference to growth charts, although the diagnosis may be evident by clinical features and radiographic abnormalities. Generally, in patients with SED congenita, the outstretched fingers reach the knee region instead of midthigh because of the short trunk, even in the neonate. The head-to-pubis (upper segment) measurements are reduced to approximately 75% of normal value, whereas the pubis-to-heel (lower segment) measurements are reduced to approximately 60-80% of normal value. [7, 12]

Adult height ranges from 90-167.5 cm. Height charts have been developed for SED congenita. The hands and feet are normal in length, in striking contrast to proximal and middle segments of the limbs, which are extremely short.

Motor development may be delayed. Intelligence is usually unaffected.

Head circumference is normal, but the face is flat, with wide-set eyes. Cleft palate is common. The neck is short, and a pectus carinatum deformity may be present in combination with a barrel-shaped chest.

Os odontoideum or odontoid hypoplasia may lead to atlantoaxial instability. Throughout growth and development, the neurologic status must be assessed in these patients to detect any deficits. [16] The signs suggestive of spinal cord compression include pyramidal tract signs—namely, spasticity, hyperreflexia, Babinski sign, and clonus. Motor weakness may be present; however, sensory examination findings are usually normal. Gait may be abnormal and should be evaluated.

Increased incidence of lumbar lordosis and associated hip flexion contractures are observed even in the newborn period. The abdomen is protuberant. Thoracic scoliosis or kyphosis may become evident in adolescence. Single and double curve patterns have been noted. Thoracic kyphosis may be severe, measuring up to 130°. Kyphosis or kyphoscoliosis can be rigid and severe.

Coxa vara of varying severity is almost universal. A waddling gait may be apparent. Coxa vara may be associated with progressive dislocation if ligamentous laxity is present. The delayed ossification of the capital femoral epiphysis predisposes the hip to deformation with flattening, lateral extrusion, hinge abduction, and premature osteoarthritis. Often, a valgus alignment of the knees may develop, associated with overgrowth of the medial femoral condyle. Genu varum may also occur, though it is rare. Clubfeet may be present in some patients.

Associated ocular anomalies include myopia with retinal detachment (>50%) and cataracts. [17] Other ocular manifestations include buphthalmos, secondary glaucoma, and strabismus; however, the corneas are clear.

Other associated conditions include deafness and abdominal or inguinal hernia. A rare form of SED congenita is associated with nephrotic syndrome.

SED tarda

In SED tarda, appearance is normal at birth. True dwarfism may not be present. Patients exhibit normal achievement of motor and cognitive milestones. Mild disproportionate trunk shortening occurs. In some patients, the condition remains unrecognized until the adolescent years, when hip pain or scoliosis develops. The diagnosis is suggested in males with disproportionately short stature in adolescence or adulthood and with a relatively short trunk and barrel-shaped chest. Upper-to-lower body segment ratio is usually about 0.8. Arm span typically exceeds height by 10-20 cm.

Atlantoaxial instability may occur secondary to odontoid hypoplasia or os odontoideum. The upper cervical spine should be assessed and a neurologic examination should be performed. [18] Scoliosis or kyphosis with an exaggerated lumbar lordosis may be present. The curves are similar to those observed in patients with adolescent idiopathic scoliosis. These curves may progress and become severe enough to require treatment.

Epiphyseal involvement in patients with SED tarda is primarily in the shoulders, hips, and knees. Involvement is symmetrical bilaterally. Changes in the hip may mimic bilateral Legg-Calve-Perthes disease. Varying degrees of coxa magna, flattening, extrusion, and subluxation may be present. Osteoarthritis of the hip is a common sequela.

Nephrotic syndrome has been reported in association with SED tarda. [19]



SED congenita


SED congenita is transmitted as an autosomal dominant trait. The gene for SED congenita has been mapped to the long arm of chromosome 12 (12q14.3). Gonadal mosaicism has been reported. Advanced paternal age is recognized as a risk factor.

Most cases result from random new mutations. Average-sized siblings have no increased risk of producing a child with SED congenita. When both parents are affected, 50% of offspring are heterozygous and affected; 25% are homozygous, which is ordinarily fatal in the first few months of life; and 25% are unaffected. When one parent is affected, the chance of transmitting this gene to each child is 50%. [20, 21, 22, 23, 24, 25]


SED congenita is caused by mutations in COL2A1 (type II collagen alpha 1 chain) on chromosome 12. [26] {red34}These result in abnormal type II collagen. Type II collagen is the major collagen of nucleus pulposus (spine), cartilage, and vitreous (eye).

Other skeletal dysplasias affected by collagen II include achondrogenesis type II, hypochondrogenesis, Kniest dysplasia, Stickler dysplasia, autosomal forms of SED tarda, and spondylometaepiphyseal (Strudwick) dysplasia.

SED tarda


SED tarda is genetically distinct from SED congenita. Although it may be transmitted as an X-linked recessive, autosomal recessive, or autosomal dominant trait, the X-linked recessive type is most common.

The X-linked form has been mapped to the Xp22 region. Only males are affected, and mothers are carriers. Carrier females have a 25% risk of having an affected son, a 25% risk of having an unaffected son, a 25% risk of having a carrier daughter, and a 25% risk of having a noncarrier daughter. None of the sons of an affected male are affected; all daughters of an affected male are carriers. A case has been reported in which a girl with Turner syndrome had a diagnosis of SED tarda. [27]


The X-linked form of SED tarda is caused by mutation in SEDL (SED late) gene. The SEDL gene has been identified on band Xp22. It encodes a protein of 140 amino acids with a role in vesicular transport. [28]

Twenty-one novel mutations affecting the SEDL gene have been recognized; the most common type of SEDL- gene disruption was deletion, representing 40% of the types of identified mutations.