Kniest dysplasia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Kniest dysplasia is a skeletal disorder that is characterized by short stature, joint disease, and problems with vision and hearing.

People with Kniest dysplasia are born with a short torso and short arms and legs. Adult height ranges from approximately 42 to 57 inches. Other skeletal problems may include a rounded upper back that also curves to the side (kyphoscoliosis), flattened bones of the spine (platyspondyly), dumbbell-shaped bones in the legs, and inward- and upward-turning feet (clubfeet). A distinguishing feature of Kniest dysplasia is abnormal cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development; most cartilage is later converted to bone. People with Kniest dysplasia have tiny holes in their cartilage, which makes the cartilage look like Swiss cheese when seen with medical imaging.

Individuals with Kniest dysplasia often have distinctive facial features, which include a round, flat face with prominent and wide-set eyes. Some affected infants are born with an opening in the roof of the mouth (cleft palate). Infants with Kniest dysplasia may also have breathing problems due to a windpipe that is too flexible. Enlarged joints that cause pain and restrict movement are another sign of Kniest dysplasia. These joint problems typically lead to early-onset arthritis. Many people with Kniest dysplasia also have hearing loss and problems with vision, such as severe nearsightedness (myopia) and tearing of the light-sensitive tissue at the back of the eye (retinal detachment).

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Kniest dysplasia is caused by variants (also called mutations) in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen, which is found in the clear gel that fills the eyeball (the vitreous) and in cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development; most cartilage is later converted to bone. Type II collagen is essential for the normal growth and development of bones and other connective tissues.

Many of the variants that cause Kniest dysplasia delete one or more of the DNA building blocks (nucleotides) in the COL2A1 gene. These variants lead to the production of an abnormal version of the COL2A1 protein, which disrupts the formation of stable, functional type II collagen molecules. The lack of functional type II collagen interferes with the development of bones and other connective tissues, which leads to the characteristic signs and symptoms of Kniest dysplasia.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Kniest dysplasia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. The majority of cases are the result of a new (de novo) variant in the gene that occurs during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These affected individuals often have no history of the disorder in their family. However, in some cases, a parent has been found to carry the same variant in a small number of their cells, which is known as somatic mosaicism.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Kniest dysplasia is a rare condition, but the exact prevalence is unknown.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal bone structure · Very frequent (99-80%)

Any anomaly in the composite material or the layered arrangement of the bony skeleton.

Abnormal cartilage collagen · Obligate (100%)

Abnormal morphology of collagen fibers in cartilage. In cartilage, collagen II, actually a collagen II:IX:XI heterofibril, is by far the most important type of collagen. A number of abnormalities may be appreciated by electron micrography or biochemical investigations, including sparse collagen fibers in the cartilage matrix.

Abnormal joint morphology · Very frequent (99-80%)

An abnormal structure or form of the joints, i.e., one or more of the articulations where two bones join.

Bell-shaped thorax · Very frequent (99-80%)

The rib cage has the shape of a wide mouthed bell. That is, the superior portion of the rib cage is constricted, followed by a convex region, and the inferior portion of the rib cage expands again to have a large diameter.

Depressed nasal bridge · Very frequent (99-80%)

Posterior positioning of the nasal root in relation to the overall facial profile for age.

Disproportionate short stature · Very frequent (99-80%)

A kind of short stature in which different regions of the body are shortened to differing extents.

Enlarged joints · Very frequent (99-80%)

Increase in size of one or more joints.

Flexion contracture of finger · Very frequent (99-80%)

Chronic loss of joint motion in a finger due to structural changes in non-bony tissue.

Other findings in the same source

From: Orphanet

Additional reported features include High myopia (Very frequent (99-80%)); Joint stiffness (Very frequent (99-80%)); Keratan sulfate excretion in urine (Very frequent (99-80%)); Proptosis (Very frequent (99-80%)); Round face (Very frequent (99-80%)); Vitreoretinopathy (Very frequent (99-80%)); Degenerative vitreoretinopathy (Very frequent (99-80%)); Delayed epiphyseal ossification (Very frequent (99-80%)); Abnormality of the epiphysis of the femoral head (Frequent (79-30%)); Aplasia/Hypoplasia of the lens (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Kniest dysplasia is Orthopaedics, with a orthopaedic specialist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• What explains the change in pain, movement or function?
• Which activities need adjustment while the diagnosis is being clarified?
• What are the roles of rehabilitation, observation and surgery in this situation?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Kniest dysplasia. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.