Tricho–rhino–phalangeal Syndrome

Overview

Tricho–rhino–phalangeal syndrome (TRPS) is a rare genetic disorder that affects hair growth, facial features, and skeletal development, particularly the fingers and toes. The name of the syndrome refers to its three hallmark features: tricho (hair), rhino (nose), and phalangeal (bones of the fingers). Individuals with TRPS typically have sparse, slow-growing scalp hair, a distinctive pear-shaped nose with a broad bridge, and cone-shaped epiphyses (ends of bones), which can lead to joint problems and short stature. TRPS is classified into three types—TRPS I, TRPS II (also known as Langer–Giedion syndrome), and TRPS III—each with varying degrees of severity and additional features.

Causes

Tricho–rhino–phalangeal syndrome is caused by mutations or deletions in the TRPS1 gene located on chromosome 8q24.12. This gene encodes a transcription factor that plays a key role in the development of hair follicles, cartilage, and bone. The disorder is typically inherited in an autosomal dominant pattern, meaning a mutation in one copy of the gene is sufficient to cause the syndrome. In some cases, it occurs due to a new (de novo) mutation with no prior family history.

• TRPS I: Caused by mutations in the TRPS1 gene alone.

• TRPS II (Langer–Giedion syndrome): Caused by deletions involving both the TRPS1 gene and the EXT1 gene, leading to additional features such as multiple exostoses (bony outgrowths).

• TRPS III: A more severe form of TRPS I, characterized by more pronounced skeletal abnormalities.

Symptoms

The symptoms of TRPS vary depending on the type and severity of the condition but typically include a combination of hair, facial, and skeletal abnormalities:

Hair Features:

• Thin, sparse, and slow-growing scalp hair

• Receding hairline or high frontal hairline

• Eyebrows and eyelashes may also be sparse

Facial Features:

• Pear-shaped nose with a broad bridge and bulbous tip

• Long philtrum (area between the nose and upper lip)

• Thin upper lip and protruding ears

Skeletal Features:

• Short stature and delayed bone age

• Short fingers and toes (brachydactyly)

• Cone-shaped epiphyses visible on X-rays

• Joint stiffness or hypermobility

• Hip malformations or hip dysplasia

Additional Features in TRPS II:

• Multiple osteochondromas (benign bone growths)

• Intellectual disability in some individuals

Diagnosis

Diagnosis of TRPS is based on clinical evaluation, radiographic findings, and genetic testing. The following steps are typically involved:

• Physical examination: Identification of characteristic facial and skeletal features, along with hair abnormalities.

• Radiographs (X-rays): Essential for detecting cone-shaped epiphyses and other bone anomalies, especially in hands and feet.

• Genetic testing: Confirms the diagnosis by identifying mutations or deletions in the TRPS1 gene (and EXT1 gene in TRPS II).

• Family history: Evaluation of inherited patterns, especially in suspected autosomal dominant inheritance.

Prenatal diagnosis may be possible if the familial mutation is known.

Treatment

There is no cure for tricho–rhino–phalangeal syndrome. Management focuses on addressing symptoms and improving quality of life through a multidisciplinary approach. Treatment options include:

• Orthopedic care: Monitoring and treatment of skeletal deformities, joint stiffness, or hip problems. Surgery may be needed for severe deformities or hip dysplasia.

• Physical therapy: To maintain joint function and mobility, especially in children with delayed motor development.

• Dental care: Management of dental anomalies that may be associated with TRPS, such as malocclusion or delayed tooth eruption.

• Cosmetic or dermatologic care: Supportive hair care and, in some cases, cosmetic solutions such as wigs or hairpieces.

• Educational support: For children with learning difficulties, particularly in TRPS II where intellectual disability may be present.

• Genetic counseling: For affected families and individuals planning a pregnancy to understand inheritance patterns and reproductive options.

Prognosis

The prognosis for individuals with tricho–rhino–phalangeal syndrome is generally favorable. Most individuals have a normal life expectancy, especially in TRPS I and III. Key factors include:

• TRPS I and III: Normal intelligence, good overall health, and manageable symptoms with appropriate care.

• TRPS II: May involve more complex challenges due to the presence of exostoses and potential intellectual disability, but many affected individuals lead fulfilling lives with support.

• Quality of life: Can be greatly improved with early diagnosis, physical therapy, orthopedic care, and educational support.

With proper multidisciplinary care and monitoring, individuals with TRPS can achieve good functional outcomes and live productive, independent lives.