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This spectrum of dysplasias result from a mutation (change) in the gene coding for type II collagen (COL2A1) found on chromosome 12. Type II collagen is a structural protein present in cartilage, the growth plate and joints, tracheal rings, as well as the eyeball and the inner ear. Therefore, if type II collagen is not able to form as it typically should in the body, then there can be differences in bone growth and shape, joint pain, floppy windpipe, as well as vision and hearing problems.

They typically have an��autosomal dominant��pattern of inheritance.

Most individuals with this dysplasia have spontaneous mutations, meaning they are the first in their family with the dysplasia. Gonadal mosaicism helps to explain why multiple children with this dysplasia can be born to unaffected parents. Once an individual has been diagnosed with a type II collagenopathy, each of their children would have a 50% chance to inherit it.

X-Ray Characteristics

Each clinical diagnosis within the spectrum can have distinct X-ray findings, but since many people’s diagnosis is “between” the well-described ones, we will list the full spectrum of associated X-ray findings here, knowing that it is rare for one person to have every finding listed below.

• Spondylodysplasia
• Epiphyseal dysplasia
• Metaphyseal dysplasia for some, like Kniest dysplasia and SEMD-Strudwick, can become apparent over time, and can demonstrate flared metaphyses and bulb-like interphalangeal joints.
• Delayed ossification in many parts of the skeleton, including: vertebral bodies of upper cervical spine, sacrum, pubic bones, capital femoral epiphyses, carpals and tarsals
• Femoral neck could be broad and short, and incompletely ossified.
• Small vertebral bodies; platyspondyly
• Hypoplasia of odontoid process of C2, and can have associated atlantoaxial instability
• In infancy, lumbar vertebral bodies may have coronal clefting.
• Coxa vara
• Progressive kyphoscoliosis
• Marked lumbar lordosis

This group of dysplasias can often be diagnosed by their characteristic clinical and radiographic features. Sometimes the diagnosis can even be suspected by prenatal ultrasonography. Clinical genetic testing of the COL2A1 gene can be performed to confirm the diagnosis.

What Musculoskeletal Problems Are Associated With Type II Collagenopathies?

Neck

Children with type II collagenopathies need to be watched closely for instability in the upper cervical spine. This atlantoaxial instability can be caused by a combination of increased flexibility and a smaller odontoid bone. The result can be cervical myelopathy, where the spinal cord is compressed, with the child developing muscle weakness, numbness, tingling and bladder incontinence. Care of these children should include regular visits with physical exams to detect the signs and symptoms of myelopathy. Regular lateral neck X-rays in flexion and extension should be monitored over time in all children with type II collagenopathies, with cervical MRI for any clinical concerns. Special Note: It is very important to discuss any surgical procedure or sedation (dental work, MRI) with your physician to ensure adequate precautions are taken to protect the neck of children with type II collagenopathies.

Spine

Curvatures of the spine, both kyphosis and scoliosis, are common in children with type II collagenopathies. Not all curves require surgery but regular follow-up, with spine X-rays, is important until a child is finished growing. Small curves can be observed and should not affect the child, but progression in young children often requires bracing or serial scoliosis casts. Growing rods can be used for larger curves, allowing continued growth through childhood while keeping the spine straight. For children near puberty, surgical fusion of the spine may be required, correcting the spine to heal in a straightened and balanced position for the future.

Joints

Type II collagenopathies as a group have epiphyseal dysplasia, resulting in irregularities within the joints. In addition, the abnormal type II collagen results in poor joint cartilage and can result in joint stiffness and pain in childhood. Joint replacement surgery (of the hips and knees) may be necessary in early adulthood, but this is variable. The presence of associated joint contractures and bony differences in type II collagenopathies makes joint replacement technically challenging.

Lower Limbs

Malformation of the hip can be present in children with type II collagenopathies, specifically coxa vara. The abnormal cartilage in these children can result in increased angulation of the femoral neck, disrupting the typical ball-and-socket relationship of the hip. Any change in the alignment of the femoral neck weakens the muscles around the hip joint and causes hip joint contractures. Surgery to realign the femoral neck is recommended in children with a limp, hip pain or worsening angulation. Children may also develop angulation at the knees as they grow: genu valgus (knock-knees) or genu varus (bow legs). Genu valgus is more common, and there is an opportunity to correct these deformities using guided growth before a child is finished growing. With routine follow-up and early detection by exam and X-ray, guided growth can be used proactively and typically avoids more invasive correction techniques, such as osteotomy, in older children.

What Other Health Issues Can Develop With Type II Collagenopathies?

Eye

Type II collagen is present in the eye, therefore these dysplasias can have associated vision concerns. Individuals can have varying levels of myopia (which can be quite extreme) and retinal detachment. Cataracts have also been noted. Regular dilated evaluation by an ophthalmologist is recommended.

Ear

Associated hearing loss can be conductive and/or sensorineural. Children with type II collagenopathies are at risk for developing recurrent ear infections due to reduction in the size of the tubes connecting the middle ear cavity to the upper throat (eustachian tube).

Cleft Palate

Cleft palate occurs for some and can lead to middle ear infections and delayed onset of speech. It is sometimes associated with Pierre Robin sequence.

Respiratory

There is type II collagen in the tracheal rings holding open the windpipe, therefore tracheomalacia (softening and collapse of the windpipe leading to breathing difficulties) and respiratory distress can occur in neonates. Some necessitate tracheostomy and ventilator with high pressures to stent open the airway, but they typically grow out of this need by school age. However, many individuals do not need this level of support.