| prognosis = Variable; generally favorable with appropriate management
| differential =
| frequency = Very rare
| prevention =
| deaths = Rare, usually related to respiratory complications
| treatment =
| medication =
| prognosis =
| frequency =
| deaths =
}}
}}
'''Kniest dysplasia''' is a rare form of [[dwarfism]] caused by a mutation in the ''[[COL2A1]]'' gene on chromosome 12.<ref>{{cite web|last1=Hirsch|first1=Larissa|title=Kniest Dysplasia|url=http://www.nemours.org/service/medical/skeletal-dysplasia/kniest.html?tab=about&kidshealth=20838|website=Nemours Children Health System|publisher=The Nemours Foundation|accessdate=21 November 2015}}</ref> The ''COL2A1'' gene is responsible for producing [[type II collagen]]. The mutation of ''COL2A1'' gene leads to abnormal skeletal growth and problems with hearing and vision. What characterizes Kniest dysplasia from other type II [[osteochondrodysplasia]] is the level of severity and the dumb-bell shape of shortened long tubular bones.<ref>{{cite book|last1=Chen|first1=Harold|title=ATLAS OF GENETIC DIAGNOSIS AND COUNSELING|date=2012|publisher=Springer US|location=New York|isbn=978-1-4614-1036-2|pages=1259–1263|doi=10.1007/978-1-4614-1037-9}}</ref>
'''Kniest dysplasia''', also known as '''Kniest syndrome''', is a rare genetic condition characterized by a distinct form of [[dwarfism]]. It arises from mutations in the ''[[COL2A1]]'' gene, located on chromosome 12, affecting the synthesis of type II [[collagen]].
This condition was first diagnosed by Dr. Wilhelm Kniest in 1952. Dr. Kniest noticed that his 50-year-old patient was having difficulties with restricted joint mobility. The patient had a short stature and was also suffering from blindness. Upon analysis of the patient's DNA, Dr. Kniest discovered that a mutation had occurred at a [[splice site]] of the COL2A1 gene.
== Signs and Symptoms ==
Characteristic clinical features include:
* Short stature with disproportionately short limbs
* Joint stiffness and limited mobility
* Distinctive facial features, including prominent forehead, flat nasal bridge, and cleft palate
* Spinal deformities such as [[scoliosis]] or [[kyphosis]]
This condition is very rare and occurs less than 1 in 1,000,000 people. Males and females have equal chances of having this condition.<ref>{{cite web|title=Kniest Dysplasia|url=https://rarediseases.org/rare-diseases/kniest-dysplasia/|website=National Organization for Rare Disorders|publisher=National Organization for Rare Disorders|accessdate=20 November 2015}}</ref> Currently, there is no cure for Kniest dysplasia. Alternative names for Kniest Dysplasia can include '''Kniest syndrome''', '''swiss cheese cartilage syndrome''', '''Kniest chondrodystrophy''', or '''metatrophic dwarfism type II.'''
== Causes ==
Kniest dysplasia results from mutations in the ''COL2A1'' gene, which encodes type II collagen, crucial for normal cartilage formation and skeletal development.
==Symptoms==
== Risk Factors ==
Because collagen plays an important role in the development of the body, people with Kniest Dysplasia will typically have their first symptoms at birth. These symptoms can include:.<ref>{{cite web|last1=Hirsch|first1=Larissa|title=Kniest Dysplasia|url=http://www.nemours.org/service/medical/skeletal-dysplasia/kniest.html?tab=about&kidshealth=20838|website=Nemours Children Health System|publisher=The Nemours Foundation|accessdate=21 November 2015}}</ref>
The primary risk factor is genetic inheritance, typically in an autosomal dominant pattern, though spontaneous mutations can occur.
*Musculoskeletal Problems [[File:Scoliosis cobb.gif|thumb|Cobb angle measurement of a dextroscoliosis]]
**Short limbs
**Shortened body trunk
**Flattened bones in the spine
**[[kyphoscoliosis]]
**[[Scoliosis]] (Lateral curvature of the spine)
**Early development of [[arthritis]]
*Respiratory problems
**[[Respiratory tract infection]]
**Difficulty breathing
*Eye problems
**Severe myopia (near-sightedness)
**[[Cataract]] (cloudiness in the lens of the eye)
**Cranial structure may elongate the eyeball, causing a thinning of the [[retina]], thereby predisposing [[retinal detachment]]
*Hearing problems
**progressive hearing loss
**ear infections
Most symptoms are chronic and will continue to worsen as the individual ages. It is essential to have regular checkups with general doctors, orthopedist, ophthalmologists, and/or otorhinolaryngologists. This will help to detect whether there are any changes that could cause concern.<ref>{{cite web|last1=John|first1=Dormans|title=Kniest Dysplasia|url=http://www.chop.edu/conditions-diseases/kniest-dysplasia#.VmfKGLjR-Ul|website=Children’s Hospital of Philadelphia|publisher=Children’s Hospital of Philadelphia|accessdate=21 November 2015|date=2014-02-23}}</ref>
== Diagnosis ==
Diagnosis typically involves:
* Clinical evaluation of physical characteristics
* Genetic testing identifying mutations in the ''COL2A1'' gene
Studies have shown that a mutated COL2A1 gene is responsible for all type II [[chondroldysplasias]], including Kniest dysplasia. It is believed that [[point mutations]] or the alteration of splice sites in COL2A1 domains will result in Kniest Dysplasia. The COL2A1 domain typically spans between [[exon]] 12 and 24. Mutations that occur at a splice donor site results in the loss of function at that site. This leads to the skipping of the exon and deletion of amino acids. The loss of these amino acids result in an abnormal procollagen II structure. The structure is not stable like the normal [[procollagen]] II structure and is normally degraded at a faster rate.<ref>{{cite web|last1=McKusick|first1=Victor|title=Kniest Dysplasia|url=http://www.omim.org/entry/156550|website=http://www.omim.org/|publisher=Johns Hopkins University|accessdate=21 November 2015}}</ref>
Treatment is supportive and focuses on managing complications and improving quality of life through:
* Orthopedic interventions and corrective surgeries
* Physical and occupational therapy to enhance mobility
* Audiological and ophthalmological care
==Diagnosis==
== Prognosis ==
The prognosis for individuals with Kniest dysplasia is generally favorable with appropriate medical and surgical management. Long-term outcomes depend largely on the severity of skeletal abnormalities and associated complications.
Kniest dysplasia is an [[autosomal dominant]] condition.<ref>{{cite journal|last1=Jenkin|first1=Henry J.|title=Hand and foot abnormalities associated with genetic diseases|pmc=3041879|website=Pubmed|publisher=Springer Link}}</ref> This means that the person only needs to have one copy of the mutated gene in order to have the condition. People with a family history are at a higher risk of having the disease than people with no family history. A random mutation in the gene can cause a person with no family history to also have the condition.
===Diagnostic techniques===
A combination of medical tests are used to diagnosis Kniest dysplasia. These tests can include:<ref>{{cite web|last1=John|first1=Dormans|title=Kniest Dysplasia|url=http://www.chop.edu/conditions-diseases/kniest-dysplasia#.VmfKGLjR-Ul|website=Children’s Hospital of Philadelphia|publisher=Children’s Hospital of Philadelphia|accessdate=21 November 2015|date=2014-02-23}}</ref>
*'''Computer Tomography Scan ([[CT scan]])''' - This test uses multiple images taken at different angles to produce a cross-sectional image of the body.
*'''[[Magnetic Resonance Imaging]] (MRI)''' - This technique proves detailed images of the body by using magnetic fields and radio waves.
*'''[[EOS Imaging]]''' - EOS imaging provides information on how musculoskeletal system interacts with the joints. The 3D image is scanned while the patient is standing and allows the physician to view the natural, weight-bearing posture.
*'''X-rays''' - X-ray images will allow the physician to have a closer look on whether or not the bones are growing abnormally.
The images taken will help to identify any bone anomalies. Two key features to look for in a patient with Kniest dysplasia is the presence of dumb-bell shaped femur bones and [[coronal clefts]] in the vertebrae. Other features to look for include:
*[[Platyspondyly]] (flat vertebral bodies)
*[[Kyphoscoliosis]] (abnormal rounding of the back and lateral curvature of the spine)
*Abnormal growth of [[epiphyses]], [[metaphyses]], and [[diaphysis]]
*Short tubular bones
*Narrowed joint spaces
'''Genetic Testing''' - A genetic sample may be taken in order to closely look at the patient's DNA. Finding an error in the COL2A1 gene will help identify the condition as a type II chondroldysplasia.
==Treatment==
Because Kniest dysplasia can affect various body systems, treatments can vary between non-surgical and surgical treatment. Patients will be monitored over time, and treatments will be provided based on the complications that arise.<ref>{{cite web|last1=Pauli|first1=Richard|title=Kniest Dysplasia Natural History|url=http://www.lpaonline.org/assets/documents/NH%20Kniest%20dysplasia1.pdf|website=http://www.lpaonline.org/|publisher=Little People of America|accessdate=21 November 2015}}</ref>
===Surgical===
*[[Spinal Fusion]] for patients with severe kyphoscoliosis
*Extension [[Osteotomy]] to help treat progressive joint limitation
*[[Surgical realignment]]
*[[Retinal Detachment repair]]
*[[Myringotomy]] (surgical procedure to relieve pressure by draining fluid from the eardrum)
===Non-surgical===
*Routine monitoring [[File:BIPAP.JPG|thumb|The setup for BPAP using a mechanical ventilator]]
Like treatment options, the prognosis is dependent on the severity of the symptoms. Despite the various symptoms and limitations, most individuals have normal intelligence and can lead a normal life.
==Recent research==
A recent article in 2015 reported a persistent notochord in a fetus at 23 weeks of gestation. The fetus had an abnormal spine, shortened long bones and a left clubfoot. After running postmortem tests and ultrasound, the researchers believed that the fetus suffered from [[hypochondrogenesis]]. Hypochondrogenesis is caused when type II collagen is abnormally formed due to a mutation in the COL2A1 gene. Normally, the cartilaginous notochord develops into the bony vertebrae in a human body. The COL2A1 gene results in malformed type II collagen, which is essential in the transition from collagen to bone. This is the first time that researchers found a persistent notochord in a human body due to a COL2A1 mutation.<ref>Codsi, Elisabeth et al. “Persistent Notochord in a Fetus with COL2A1 Mutation.” Case Reports in Obstetrics and Gynecology 2015 (2015): 935204. PMC. Web. 21 Nov. 2015.</ref>
==Eponym==
It is named for Wilhelm Kniest.<ref>{{WhoNamedIt|synd|2170}}</ref>
==References==
{{reflist|2}}
== Prevention ==
Genetic counseling is recommended for affected families to understand recurrence risks and to aid in family planning.
Variable; generally favorable with appropriate management
Frequency
Very rare
Deaths
Rare, usually related to respiratory complications
Kniest dysplasia, also known as Kniest syndrome, is a rare genetic condition characterized by a distinct form of dwarfism. It arises from mutations in the COL2A1 gene, located on chromosome 12, affecting the synthesis of type II collagen.
Kniest dysplasia results from mutations in the COL2A1 gene, which encodes type II collagen, crucial for normal cartilage formation and skeletal development.
The prognosis for individuals with Kniest dysplasia is generally favorable with appropriate medical and surgical management. Long-term outcomes depend largely on the severity of skeletal abnormalities and associated complications.
