About Type II Collagenopathies

Type II collagenopathies are a wide spectrum of skeletal dysplasias that include: hypochondrogenesis, spondyloepiphyseal dysplasia congenita, Kniest dysplasia and spondyloepimetaphyseal dysplasia-Strudwick type, among others. Years ago, each of these clinical diagnoses were based solely on physical features, medical history and X-ray findings. However, we now know they all have the same underlying cause, which is a change in the type II collagen gene. There are also many people with a skeletal dysplasia who do not have features that neatly fit into a well-described skeletal dysplasia clinical diagnosis but are found to have a change in this same causative gene. Given this, medical monitoring is similar for everyone with a dysplasia in this spectrum and will be explained together here.

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What Causes Type II Collagenopathies?

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.

How Are Type II Collagenopathies Inherited?

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.

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What Are the Characteristics of Type II Collagenopathies?

There is variation between families as well as between the type II collagenopathies, so the below listed features should be thought of as associated, but not universal.

Face and Skull

  • Large head size relative to trunk
  • Round and flat face
  • Wide, prominent forehead and eyes
  • Depressed nasal bridge
  • Depressed chin
  • Cleft palate can be present


Trunk, Chest and Spine


Arms and Legs

  • There initially can be short limbs compared to the torso, but the proportions can change as trunk shortens and becomes kyphoscoliotic.
  • Rhizomelic shortening of the limbs
  • Ligamentous laxity
  • Flexed and abducted hips
  • Knock-knees
  • Flat feet
  • Some, like Kniest dysplasia, can have widened joints in the arms and legs, that may not be able to bend or straighten fully (contractures).

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

How Is a Type II Collagenopathy Diagnosed?

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?


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.


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.


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?


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.


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.


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.

What Should I Watch for With Type II Collagenopathies?

Generally, all skeletal dysplasias warrant multidisciplinary attention. Regular assessment by a team of specialists with an understanding of skeletal dysplasias will provide the most comprehensive care.

Regular assessment by a pediatric orthopedic surgeon is recommended, to include monitoring of neck, back and lower extremities.

Any change in gait pattern should be taken seriously. This may be associated with tiredness, decrease in meeting motor milestones or walking distance, reduced endurance, or pain. Any alterations in sensation (tingling or numbness in arms and legs) or loss of bowel/ bladder control can be indicative of spinal cord irritation or compression and should be evaluated.

Changes in trunk symmetry, shoulder height differences, prominence of one hip, or rib prominence on bending forwards may indicate a changing curvature in the spine.

Assessment of cleft palate at birth, and evaluation of hearing through childhood is recommended. Sensorineural hearing loss tends to be stable, but conductive hearing loss can fluctuate.

Regular dilated ophthalmic examinations are also recommended to assess for progressive myopia, as well as retinal health.

Given the differences in body proportions, it is inappropriate to use the developmental charts of a typical child to assess the gross motor skills of a child with a type II collagenopathy. Given risk of cervical spine instability, care should be taken to not push development of head control beyond what the child is able to achieve at that time. If concerns, should first assess for a potential neurologic cause at the c-spine.

Overall, we also recommend you talk about the type II collagenopathy — both with your child and others — as a difference rather than a problem. Your attitude can help your child develop good self-esteem. Treat them according to age and not size and encourage others to do the same. Also, find ways to adapt. For example, get a light switch extender and a stepstool so your child can turn the lights on and off and get to the sink independently to wash their hands. Besides in the home, also encourage your child’s school to make modifications/accommodations to maximize their independence in an age-appropriate way. Provide them with the tools to help them be successful.