TRPS2, also known as Langer-Giedion syndrome, is an exceptionally uncommon hereditary disorder that affects multiple systems in the body. This condition is characterized by cognitive impairment and various other abnormalities, such as excessive skin folds, multiple bony growths, distinct facial features, and cone-shaped ends of the finger bones. The severity and range of symptoms can differ significantly among individuals. TRPS2 is typically inherited in an autosomal dominant manner, although sporadic cases have also been documented. The underlying cause of TRPS2 is the absence of genetic material, specifically chromosomal deletions on chromosome 8, which often involve the TRPS1 and EXT1 genes. The size of the deletion can vary from person to person.
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TRPS II, also known as Trichorhinophalangeal syndrome type II, is a medical condition characterized by various abnormalities in the body. These abnormalities include bone and joint malformations, distinct facial features, intellectual disability, and abnormalities in the skin, hair, teeth, sweat glands, and nails. The name of the condition itself indicates the areas of the body that are commonly affected, namely the hair, nose, fingers, and toes.
One of the prominent features of TRPS II is the presence of multiple benign bone tumors called osteochondromas. These tumors can range from a few to several hundred in number and typically develop from infancy to early childhood, ceasing their growth during adolescence. Depending on their location, osteochondromas can cause pain, limited joint movement, or damage to blood vessels or the spinal cord. Individuals with TRPS II may also experience reduced bone mineral density and exhibit slow growth, resulting in short stature. The ends of the bones in the fingers or toes may have an abnormal cone-shaped appearance, and the fingernails and toenails are often thin and abnormally shaped.
Children with TRPS II may initially display hypermobility in their joints, but as osteochondromasdevelop, the joints become stiffer, leading to decreased mobility. Additionally, individuals with TRPS II may experience hip dysplasia, a misalignment of the hip joints, which can occur in early adulthood or during infancy and childhood.
The characteristic appearance of individuals with TRPS II includes thick eyebrows, a broad nose with a rounded tip, a smooth area between the nose and upper lip (philtrum), a thin upper lip, and small teeth that can be either decreased or increased in number. Sparse scalp hair is a common feature, particularly in males who may experience significant hair loss, often leading to near or complete baldness.
TRPS II is caused by the absence of genetic material on chromosome 8. The extent of the deletion varies among individuals, with larger deletions resulting in more features. TRPS II is linked to the loss of multiple genes on chromosome 8, including TRPS1, EXT1, and RAD21. The absence of the EXT1 gene causes multiple osteochondromas, while the loss of TRPS1 leads to bone and facial abnormalities. Deletion of the RAD21 gene may contribute to intellectual disability. Other genes in this region likely contribute to additional features. TRPS II is considered a contiguous gene deletion syndrome. TRPS I is a similar condition caused by changes in the TRPS1 gene, but it does not have osteochondromas or intellectual disability. For more information, refer to the expanded section.
In most instances, TRPS II is not passed down through generations, but rather arises spontaneously during the development of reproductive cells (eggs or sperm) in an affected individual's parent. These occurrences occur in individuals whose families have no previous history of the disorder. However, in a few rare cases, individuals with TRPS II have inherited the chromosomal deletion from a parent who also has the condition.
TRPS II is classified as an autosomal dominant condition since the presence of one altered chromosome 8 in each cell is enough to trigger the disorder.
Most cases of TRPS II are not inherited, but occur as random events during the formation of reproductive cells (eggs or sperm) in a parent of an affected individual. These cases occur in people with no history of the disorder in their family. In a very small number of cases, people with TRPS II have inherited the chromosomal deletion from a parent with the condition.
TRPS II is considered an autosomal dominant condition because one copy of the altered chromosome 8 in each cell is sufficient to cause the disorder.
- Chromosome 8q24.1 deletion syndrome
- Giedion-Langer syndrome
- Langer-Giedion syndrome
- Tricho-rhino-phalangeal syndrome type II
- Trichorhinophalangeal syndrome with exostosis
- TRPS II