Tricho-rhino-phalangeal syndrome (TRPS) is a rare, inherited condition present from birth that affects the development of the skeletal system, hair, and facial structures. The name is derived from the main body parts involved: tricho (hair), rhino (nose), and phalangeal (fingers and toes). TRPS is classified as an ectodermal dysplasia due to its impact on structures like hair and nails. The characteristic physical features of the disorder vary in severity among affected individuals.
Defining the Syndrome and Its Classifications
TRPS is a complex, rare genetic disorder categorized into three distinct types, differentiated primarily by the severity of skeletal involvement and additional features.
Type I represents the classic form, characterized by sparse hair, distinctive facial shape, and hand and foot abnormalities. Type III is a more severe expression of Type I, involving pronounced shortening of the fingers and toes (severe brachydactyly) and more significant skeletal issues.
Type II, also known as Langer-Giedion syndrome, is clinically distinct. This form includes all Type I features but also involves multiple osteochondromas—benign, cartilage-capped bony growths. Type II is also associated with mild-to-moderate intellectual disability, a feature not typically seen in Type I or Type III.
Clinical Features and Physical Manifestations
The characteristic features of TRPS are noticeable across multiple body systems. The most consistent finding is hypotrichosis: sparse, thin, and slow-growing hair on the scalp. This hair is often brittle, and males may experience near or complete baldness relatively early.
The craniofacial appearance is marked by a broad nose with a rounded or pear-shaped tip. Other facial features include a long, smooth philtrum (the groove between the nose and upper lip) and a thin upper lip.
Skeletal abnormalities primarily involve the hands and feet. Affected individuals typically present with brachydactyly (unusually short fingers and toes). X-rays of the hands reveal cone-shaped epiphyses, which are abnormal, pointed formations at the ends of the long bones in the fingers.
Other skeletal issues include short stature and potential hip abnormalities, such as hip dysplasia or Perthes-like disease, which involves the breakdown of bone tissue in the hip joint. Type II individuals specifically develop multiple exostoses (palpable bony lumps) on the long bones.
The Genetic Basis of TRPS
TRPS is caused by an alteration in the TRPS1 gene, located on the long arm of chromosome 8 (8q23.3). This gene provides the instructions for creating the TRPS1 protein.
The TRPS1 protein is a zinc finger transcription factor that resides in the cell nucleus and regulates other genes. Its primary function is to act as a repressor, turning off the expression of genes that control cartilage and bone growth. A mutation in the TRPS1 gene results in an altered protein with a reduced ability to perform this regulatory function.
Type I and Type III are caused by a heterozygous pathogenic variant in the TRPS1 gene. Type II is typically caused by a larger contiguous gene deletion on chromosome 8. This deletion removes TRPS1 and neighboring genes, such as EXT1 and RAD21. The loss of these adjacent genes accounts for the additional features seen in Type II.
The syndrome follows an autosomal dominant inheritance pattern, meaning only one copy of the altered gene is needed to develop the condition. While many individuals inherit the altered gene, a significant number of cases result from a new, spontaneous genetic change, known as a de novo mutation.
Diagnosis and Lifetime Symptom Management
Diagnosis begins with a clinical evaluation based on characteristic physical features, such as sparse hair, the distinctive pear-shaped nose, and short fingers.
Confirmation involves radiographic imaging, specifically X-rays of the hands and feet. These images visualize the hallmark skeletal feature: cone-shaped epiphyses in the phalanges. A definitive diagnosis is achieved through genetic testing, which identifies the specific TRPS1 gene mutation or the larger deletion associated with Type II.
Since there is no curative treatment, management focuses on a supportive, multidisciplinary approach to address symptoms throughout life. Orthopedic care monitors and treats skeletal issues, including managing joint pain, addressing hip deformities like dysplasia, and potentially utilizing surgery, such as hip replacement, due to progressive joint degeneration.
Dermatological care addresses hair abnormalities, often involving specialized hair care advice or the use of wigs. Individuals with Type II require specialized educational and developmental support to manage mild-to-moderate intellectual disability. Continuous monitoring by a team of specialists is necessary to optimize function and quality of life.