Trichorhinophalangeal syndrome type I (TRPS1) is an extremely rare inherited multisystem disorder. TRPS1 is characterized by thin, sparse scalp 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 rounded (bulbous) "pear-shaped" nose, an abnormally small jaw (micrognathia), dental anomalies, and/or unusually large (prominent) ears. In most cases, the fingers and/or toes may be abnormally short (brachydactyly) and curved. In addition, affected individuals may exhibit short stature. The range and severity of symptoms may vary from case to case. In most cases, Trichorhinophalangeal syndrome type I has autosomal dominant inheritance.
The range and severity of symptoms of individuals with trichorhinophalangeal syndrome type I may vary from case to case. Most cases are characterized by thin, sparse scalp hair, unusual facial features, and multiple abnormalities affecting the “growing ends” (epiphyses) of certain bones, especially those in the hands and feet.
The hair of affected infants may be markedly thin and sparse at birth (congenital) and is usually fine and brittle and/or may grow slowly. Affected individuals may lose most or all of their scalp hair (alopecia) at a young age, in some cases, by the second decade of life. In many cases, the eyebrows may be unusually thick near the nose and abnormally sparse by the temples.
Characteristic facial features may include a rounded (bulbous), “pear-shaped” nose; a thin upper lip; an abnormally long groove (philtrum) on the upper lip, and/or a groove in the chin. Affected individuals may also have abnormally large (prominent) ears, an unusually small lower jaw (micrognathia), and/or small, discolored, and abnormally soft (carious) teeth that may be abnormally positioned (malocclusion). In some cases, extra (supernumerary) teeth may also be present.
In most cases, affected individuals exhibit abnormalities of the fingers and/or toes including permanent fixation of the fifth fingers in a bent position (clinodactyly) and/or abnormal “cone-shaped” bones in the fingers (middle phalanges) and toes (epiphyseal coning). In addition, certain bones in the hands (metacarpals) and feet (metatarsals) may be abnormally short and curved. In some cases, the nails may be unusually thin and malformed (dysplastic). In rare cases, affected individuals may also have an abnormally short forearm bone (ulna) and/or flat feet (pes planus).
As individuals with TRPS1 age, most exhibit delayed bone age and growth retardation, resulting in short stature. In some cases, affected individuals may develop pain and limitation of movements in the hips and/or hands; inflammation and swelling (arthritis) in the fingers, elbows, and/or spine may also develop. Some individuals with TRPS1 may develop hip problems similar to those of people with Legg-Calve-Perthes disease. These include progressive degeneration of the end portion (head) of the thigh bone (capital femoral epiphyseal osteonecrosis). (For more information on Legg-Calve-Perthes disease, see the Related Disorders section of this report.)
Individuals with TRPS1 may also exhibit other physical abnormalities including abnormal prominence of the breast bone (pectus carinatum), an unusual “wing-like” shape of the shoulder blades (scapula), abnormal side-to-side curvature of the spine (scoliosis), and/or backward curvature of the spine (lordosis). In some cases, affected individuals may also experience frequent respiratory infections.
Trichorhinophalangeal syndrome type I is a rare genetic disorder with autosomal dominant inheritance. 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.
Researchers have located a gene involved in TRPS1. The gene, known as the TRPS1 gene, is located on the long arm (q) of the 8th chromosome (8q24.12). Some cases of TRPS1 occur due to disruption or changes (mutations) of this gene.
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 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
The physical findings associated with TRPS1 may vary greatly from case to case (variable expressivity). For example, some physical characteristics (e.g., abnormal rounding of the nose, short stature) may be more severe in some cases than in others.
In rare cases, TRPS1 may occur as an autosomal recessive trait. Most recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. However, some individuals with TRPS1 may develop TRPS1 due to haploinsufficiency, the circumstance in which the one normal gene cannot produce enough protein to assure normal function.
Trichorhinophalangeal syndrome type I is an extremely rare inherited disorder that affects males and females in equal numbers. In those individuals with mild symptoms, a diagnosis may be easily missed or go unreported. Therefore, it is difficult to determine the true frequency of this disorder in the general population. Many researchers suspect there may be a higher incidence of TRPS1 than is actually reported in the medical literature.
The diagnosis of TRPS1 may be suspected upon identification of characteristic physical features (e.g., rounded [bulbous] nose; thin, sparse hair; etc.). The diagnosis may be confirmed by a thorough clinical evaluation, a detailed patient history, and X-ray studies of the skeleton that reveal distinctive abnormalities of the hands and feet (e.g., epiphyseal coning). Molecular genetic testing can reveal mutations of the TRPS1 gene.
The treatment of TRPS1 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, speech pathologists, orthopedic surgeons, physicians who evaluate and treat skin problems (dermatologists), and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.
Specific therapies for the treatment of TRPS1 are symptomatic and supportive. Various orthopedic techniques, including surgery, may be performed to help treat and/or correct skeletal abnormalities. Additional therapeutic and/or supportive measures may be necessary in some cases.
Genetic counseling may be of benefit for affected individuals and their families.
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Online Mendelian Inheritance in Man (OMIM). Victor A. McKusick, Editor; Johns Hopkins University, Last Edit Date 10/3/95, Entry Number 190350; Last Edit Date 4/29/94, Entry Number 275500; Last Edit Date 8/7/96, Entry Number 305100.
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