Trichorhinophalangeal syndrome type 1

Alternate names

TRPS1; Giedion syndrome

Definition

Trichorhinophalangeal syndrome type I (TRPS I) is a condition that causes bone and joint malformations; distinctive facial features; and abnormalities of the skin, hair, teeth, sweat glands, and nails.

The name of the condition describes some of the areas of the body that are commonly affected: hair (tricho-), nose (rhino-), and fingers and toes (phalangeal).

Epidemiology

TRPS I is a rare condition; its prevalence is unknown. In the Netherlands, at least 35 people have TRPS I.

Cause

• TRPS I is caused by mutations in the TRPS1 gene.
• This gene provides instructions for making a protein that is found within the cell nucleus where it interacts with specific regions of DNA to turn off (repress) the activity of certain genes.
• Research suggests that the TRPS1 protein plays a role in regulating genes that control the growth of bone and other skeletal tissues.

Gene muatations

• TRPS1 gene mutations lead to the production of an altered TRPS1 protein.
• The altered protein has a reduced ability to control the activity of genes that regulate the growth of bone and other tissues, leading to abnormal bones in the fingers and toes, joint abnormalities, distinctive facial features, and other signs and symptoms of TRPS I.
• A condition similar to TRPS I is caused by the loss of the TRPS1 gene and its neighboring genes.
• This condition, called trichorhinophalangeal syndrome type II (TRPS II), has many of the same signs and symptoms of TRPS I, as well as multiple benign (noncancerous) bone tumors called osteochondromas and intellectual disability.
• These additional features are associated with the loss of genes near TRPS1.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

• TRPS I is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
• In most cases, an affected person inherits the mutation from one affected parent.
• Some cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Signs and symptoms

• In people with TRPS I, the ends (epiphyses) of one or more bones in the fingers or toes are abnormally cone-shaped.
• Additionally, the fingernails and toenails are typically thin and abnormally formed.
• Affected individuals often have short feet.
• Individuals with TRPS I may have a misalignment of the hip joints (hip dysplasia), which often develops in early adulthood but can occur in infancy or childhood.
• Children with TRPS I often have an unusually large range of movement (hypermobility) in many of their joints.
• Over time, however, the joints may break down (degenerate), leading to joint pain and a limited range of joint movement.
• The characteristic appearance of individuals with TRPS I involves thick eyebrows; a broad nose with a rounded tip; large ears, a long, smooth area between the nose and the upper lip (philtrum); a thin upper lip; and small teeth that are either decreased (oligodontia) or increased (supernumerary) in number. Almost all affected individuals have sparse scalp hair.
• Males are particularly affected by hair loss with many being nearly or completely bald soon after puberty.
• Some children with this condition have loose skin, but the skin becomes tighter over time.
• Individuals with TRPS I may experience excessive sweating (hyperhidrosis).

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Bulbous nose
• Clinodactyly of the 5th finger(Permanent curving of the pinkie finger)
• Cone-shaped epiphysis(Cone-shaped end part of bone)
• Frontal bossing
• Long philtrum
• Long upper lip(Elongation of upper lip)
• Macrotia(Large ears)
• Micrognathia(Little lower jaw)
• Protruding ear(Prominent ear)
• Short distal phalanx of finger(Short outermost finger bone)
• Short metacarpal(Shortened long bone of hand)
• Short metatarsal(Short long bone of foot)
• Short stature(Decreased body height)
• Shortening of all phalanges of fingers(Shortening of all finger bones)
• Sparse and thin eyebrow(Thin, sparse eyebrows)
• Sparse eyelashes(Scant eyelashes)
• Triangular face(Face with broad temples and narrow chin)

30%-79% of people have these symptoms

• Avascular necrosis of the capital femoral epiphysis
• Camptodactyly of finger(Permanent flexion of the finger)
• Fragile nails(Brittle nails)
• High palate(Elevated palate)
• Hyperlordosis(Prominent swayback)
• Increased number of teeth(Extra teeth)
• Leukonychia(White discoloration of nails)
• Muscular hypotonia(Low or weak muscle tone)
• Pectus carinatum(Pigeon chest)
• Scoliosis

Diagnosis

Typical clinical findings including facial features, ectodermal manifestations, and distal limb anomalies and radiographic findings of cone-shaped epiphyses Suggestive findings of TRPS I and identification of a heterozygous pathogenic variant in TRPS1.[1].

Treatment

Management is principally supportive. [2]. Ectodermal issues:

• Advice about hair care and use of wigs
• Extraction of supernumerary teeth can be considered.

Skeletal issues:

• In those with short stature with and without proven growth hormone deficiency, use of human growth hormone therapy has had variable results
• The treatment of joint pain is use of analgesics (e.g., NSAIDs or other non-opiates)
• Physiotherapy may aid mobility
• Occupational therapy can benefit fine motor skills/tasks
• Prosthetic hip implantation should be considered in those with severe hip dysplasia.

NIH genetic and rare disease info

• NIH info on Trichorhinophalangeal syndrome type 1

Trichorhinophalangeal syndrome type 1 is a rare disease.

Trichorhinophalangeal syndrome type 1 Resources
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