SNP Shot: Genomic Insights

Trichorhinophalangeal syndrome type II (TRPS II) is a genetic disorder characterized by a combination of features, including skeletal and joint abnormalities, distinctive facial characteristics, intellectual disability, and problems affecting the skin, hair, teeth, sweat glands, and nails. The name TRPS II reflects the involvement of the hair (tricho-), nose (rhino-), and fingers and toes (phalangeal).

A common feature of TRPS II is the development of multiple benign bone tumors called osteochondromas. Individuals with TRPS II may have anywhere from a few to hundreds of these growths. Osteochondromas typically start appearing in infancy or early childhood and stop forming around adolescence. Their location can cause pain, limit joint movement, or damage blood vessels or the spinal cord. People with TRPS II may also have reduced bone mineral density (osteopenia) and often experience slow growth both before and after birth, resulting in short stature. In this condition, the ends (epiphyses) of finger or toe bones are often abnormally cone-shaped, and the fingernails and toenails are typically thin and malformed.

Children with TRPS II frequently exhibit an unusually wide range of joint motion (hypermobility). However, as osteochondromas develop, generally beginning between infancy and mid-childhood, the joints may become stiff, leading to decreased mobility. Hip dysplasia, a misalignment of the hip joints, is also common in TRPS II, often developing in early adulthood, but it can occur in infancy or childhood.

The distinctive facial appearance of individuals with TRPS II includes thick eyebrows, a broad nose with a rounded tip, a long and smooth philtrum (the area between the nose and upper lip), a thin upper lip, and small teeth that may be fewer in number than normal (oligodontia) or excessive (supernumerary). Almost all affected individuals have sparse scalp hair. Hair loss is particularly pronounced in males, with many experiencing near or complete baldness shortly after puberty. Some children with TRPS II may have loose skin, which tends to tighten over time. Excessive sweating (hyperhidrosis) may also occur.

Most individuals with TRPS II experience mild intellectual disability.

Inheritance:

Most cases of TRPS II are not inherited. Instead, they result from new, random genetic changes occurring during the formation of egg or sperm cells in a parent. These individuals are the first in their family to have the disorder. In rare instances, TRPS II is inherited from a parent who also has the condition due to a chromosomal deletion. TRPS II is considered an autosomal dominant condition, meaning that only one copy of the altered chromosome 8 in each cell is sufficient to cause the disorder.