Kniest dysplasia

Human disease

Kniest dysplasia is a rare form of dwarfism caused by a mutation in the COL2A1 gene on chromosome 12. 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. This condition was first described by Dr. Wilhelm Kniest in 1952, publishing the case history of a 3 1⁄2 year old girl. Dr. Kniest noticed that his patient had bone deformities and restricted joint mobility. The patient also had short stature and later developed blindness, resulting from retinal detachment and glaucoma. Upon analysis of the patient's DNA in 1992, sequencing revealed deletion of a 28 base pair sequence encompassing a splice site in exon 12 and a G to A transition in exon 50 of the COL2A1 gene. 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. 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.

Phenotype Location Gene/Locus Gene/Locus MIM Number Inheritance Phenotype MIM Number Phenotype Mapping Key Kniest Dysplasia 12q13.11 COL2A1 120141 Autosomal Dominant 156550 3

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.

Kniest dysplasia is an autosomal dominant condition. 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.

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.

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.

It is named for Wilhelm Kniest.