Trichorhinophalangeal syndrome type III (TRPS3), also known as Sugio-Kajii syndrome, is an extremely rare inherited multisystem disorder. TRPS3 is characterized by fine, thin light-colored hair; unusual facial features; abnormalities of the fingers and/or toes; and multiple abnormalities of the "growing ends" (epiphyses) of the bones (skeletal dysplasia), especially in the hands and feet. Characteristic facial features may include a pear-shaped or rounded (bulbous) nose; an abnormally long prominent groove (philtrum) in the upper lip; and/or abnormalities such as delayed eruption of teeth. In addition, affected individuals also exhibit severe shortening of the fingers and toes (brachydactyly) due to improper development of bones in the hands and feet (metacarpophalangeal shortening). Additional features often include short stature (dwarfism) and/or additional skeletal abnormalities. The range and severity of symptoms may vary from case to case. TRPS3 is thought to have autosomal dominant inheritance.
The symptoms of trichorhinophalangeal syndrome type III may vary in range and severity from case to case. Common symptoms include fine, thin light-colored hair; unusual facial features; multiple abnormalities affecting the “growing ends” (epiphyses) of the certain bones, particularly those in the hands and feet; severe shortening of the fingers and toes (brachydactyly); and/or additional skeletal abnormalities.
Infants with TRPS3 may exhibit markedly thin, sparse scalp hair at birth (congenital). The hair may also be usually fine and brittle. Affected infants also have several characteristic facial features. These may include a pear-shaped or rounded (bulbous) nose with small, underdeveloped nostrils (hypoplastic alae nasi); an abnormally long broad groove (philtrum) on the upper lip as well as a long, protruding upper lip; underdeveloped cheek bones (malar hypoplasia); and/or an abnormally prominent upper jaw bone (maxilla). Affected individuals may also exhibit dental abnormalities including delayed eruption and/or abnormal positioning (malocclusion) of the teeth.
In most cases, individuals with TRPS3 have several abnormalities of the hands and feet. Affected individuals may exhibit severe shortening of the fingers and toes (brachydactyly) due, in part, to incomplete development of bones in the hands (e.g., metacarpals), the feet (e.g., metatarsals), and the fingers and toes (phalanges). In addition, the “growing ends” (epiphyses) of the bones of the fingers and toes may be abnormally “cone-shaped” and may harden (ossify) before growth is complete (premature fusion). Most affected individuals exhibit permanent fixation of the fingers in a bent position (clinodactyly).
Affected individuals may also exhibit additional skeletal abnormalities including short stature, inflammation of the bone and cartilage in the spinal column (osteochondritis), abnormal sideways curvature of the spine (thoracic scoliosis), abnormal prominence of the breast bone (pectus carinatum), and/or limited movements of certain joints. In addition, some females affected by this disorder may exhibit abnormally broad hip development with advancing age.
Trichorhinophalangeal syndrome type III is inherited in an autosomal dominant trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
Most cases of TRPS3 occur due to changes or disruptions (mutations) of the TRPS1 located on the long arm of chromosome 8 (8q24.12). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 8q24.12″ refers to band 24.12 on the long arm of chromosome 8. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
The physical findings and symptoms associated with TRPS3 may vary greatly from case to case (variable expressivity).
Trichorhinophalangeal syndrome type III is an extremely rare disorder that, in theory, affects males and females in equal numbers. However, of the reported cases, most affected individuals have been female. Approximately 15 cases have been reported in the medical literature.
A diagnosis of trichrhinophalangeal syndome type III may be suspected based upon identification of characteristic physical features (e.g., fine, sparse hair; facial abnormalities; etc.). The diagnosis may be confirmed by a thorough clinical evaluation, a detailed patient history, and X-ray studies of the skeleton that reveal severe shortening of bones in the hands and feet (i.e., metacarpals, metatarsals, and phalanges) and the abnormal development of the “growing ends” (epiphyses) of the phalangeal bones (epiphyseal coning).
The treatment of TRPS3 is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, dental specialists, orthopedic surgeons, and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.
Specific therapies for the treatment of TRPS3 are symptomatic and supportive. Various orthopedic techniques, including surgery, may be used to help treat and/or correct skeletal abnormalities. Physical therapy may be prescribed to help improve the range of motion in the hips and various joints. Additional therapeutic and/or supportive measures may be necessary in some cases.
Genetic counseling will be of benefit for affected individuals and their families. Other treatment in symptomatic and supportive.
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McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). Johns Hopkins University, Last Edit Date 6/1/94, Entry Number 190351; Last Edit Date 8/14/96, Entry Number 180870.