Kniest Dysplasia

Dr. Wilhelm Kniest first described this condition in 1952 at the Children’s Hospital of the University of Jena. It was previously thought to be a variant of metatropic dysplasia, sometimes called Pseudometatropic or Metatropic dysplasia Type II. Kniest dysplasia is a rare form of cartilage dysplasia; the estimated incidence is less than 1 in 1,000,000 (4).

 
How Kniest Dysplasia Is Inherited

Kniest syndrome is inherited in an autosomal dominant manner (1).

 
Causes of Kniest Dysplasia

Kniest dysplasia results from a mutation in the gene coding for Collagen Type II (COL2A1) found on chromosome 12. Collagen Type II is a structural protein present in intervertebral discs, cartilage, and the eyeball (1).

 
Physical Characteristics

Kniest dysplasia is a rare, severe form of cartilage dysplasia that causes short-stature, spine deformities, near-sightedness, and large, stiff joints.

Face & Skull
  • Large head relative to trunk
  • Round and flat face
  • Wide, prominent forehead and eyes
  • Flattened nose
  • Wide mouth
  • Depressed chin
  • Cleft palate present in 50% of patients.
Trunk, Chest, & Spine:
Arms & Legs:
  • At birth, short limbs compared to the torso; proportions change as trunk shortens and becomes kyphotic.
  • Rhizomelic shortening of the limbs
  • Knock-knees
  • Flat feet
  • Widened joints in the arms and legs, oftentimes with painful contractures and limited motion
What are the X-ray characteristics?

The radiographic features of Kniest patients include broad and short femoral necks. Retarded ossification of capital femoral epiphyses usually appearing in ages 2-3 is typical. Ultimately, the epiphyses are large and flattened. Platyspondyly with anterior wedging of vertebral bodies is also characteristic.

In newborns, lumbar bodies exhibit coronal clefts. The ilia are broad ilia with hypoplasia of the basilar portions. By age 3, the pelvis has “dessert-cup” shape. The tubular bones are short with flared metaphyses and large, deformed epiphyses. Hand radiographs reveal osteoporosis, large carpal centers, and “bulb-like” interphalangeal joints with narrow joint spaces.

 
Making the Diagnosis

Kniest dysplasia is usually recognized at birth and can be detected via ultrasound. It is identified by its characteristic clinical and X-ray features. Radiographs especially help to differentiate Kniest dysplasia from other
type II collagenopathies. Clinical genetic testing by direct DNA analysis is also available.

 
Musculoskeletal Problems
Atlantoaxial Instability

Atlantoaxial instability should be ruled out in all children with Kniest syndrome at diagnosis (see SED for details). The instability results from the skull moving abnormally in relation to the first cervical vertebra (called the "atlas"). It can cause spinal cord compression and impingement. Lateral neck x-rays in flexion and extension should be performed before administering a general anesthetic to these children.

Spine

Kyphosis occurs at the thoracolumbar junction in addition to scoliosis. No definite conclusions have been reached regarding the management of
spinal deformities in Kniest children, but the same general principles of bracing apply to control the curve. Experience is limited on spine fusions in this group.

Joints

Stiffness, contractures and degenerative arthritis develop early in life. The cartilage of Kniest patients is soft and mechanically incompetent. Regular physical therapy is aimed at preserving movement and preventing further stiffness and permanent contractures.

 
Problems Elsewhere in the Body
Eye

As with other disorders that affect type II collagen, such as SEDc, children with Kniest dysplasia develop serious eye problems, including severe myopia (near-sightedness), retinal detachment, and cataracts. This makes regular ophthalmologic follow-up a necessity. Eyes may also protrude.

Ear

Progressive conductive hearing loss is common due to repeated middle ear infections. This can be made worse by associated sensori-neural deafness to high-pitched sounds.

Respiratory

Tracheomalacia (softening and collapse of the windpipe leading to breathing difficulties) and respiratory distress are common in neonates. Upper respiratory tract infections occur frequently leading to conductive hearing loss.

Mouth

Cleft palate occurs in 50% of patients and oftentimes leads to middle ear infections and delayed onset of speech. It should be repaired once the infant is stable enough to withstand surgical procedures.

 
What to Look For

Due to eye complications, including severe myopia (near-sightedness), retinal detachment, and cataracts, regular ophthalmologic follow-ups are a necessity for Kniest Dysplasia.

Kniest dysplasia is characterized by early onset arthritis in multiple joints that significantly interferes with function. Joint replacement surgery may become necessary in the second decade due to disabling symptoms.

Generally all skeletal dysplasias warrant multidisciplinary attention. Regular assessment by an orthopedist, geneticist, pediatrician, dentist, neurologist, and physical therapist will provide the most comprehensive treatment.

 
References
  1. Jones, Kenneth L. Recognizable Patterns of Human Malformation. Philadelphia, PA: Elsevier Saunders. 2006.
  2. Scott, Charles I. Dwarfism. Clinical Symposium, 1988; 40(1);26-29.
  3. Spranger, Jurgen W. Brill, Paula W. Poznanski, Andrew. Bone Dysplasias: An Atlas of Genetic Disorder of Skeletal Development. Oxford: Oxford University Press. 2002.
  4. The Greenberg Center for Skeletal Dysplasias at John Hopkins University Type II Collagen Conditions Clinical Summaries

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