Trichorhinophalangeal syndrome type 2

Alternate names

TRPS 2; Langer Giedion Syndrome; LGS; Deletion 8q24.1; Monosomy 8q24.1; Trichorhinophalangeal syndrome type II; Giedion-Langer syndrome

Definition

Trichorhinophalangeal syndrome type II (TRPS II) is a condition that causes bone and joint malformations; distinctive facial features; intellectual disability; 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 II is a rare condition; its prevalence is unknown.

Cause

• TRPS II is caused by the deletion of genetic material on the long arm (q) of chromosome 8.
• The size of the deletion varies among affected individuals; studies suggest that larger deletions tend to result in a greater number of features than do smaller deletions.
• The signs and symptoms of TRPS II are related to the loss of multiple genes on chromosome 8.
• The TRPS1, EXT1, and RAD21 genes are missing in people with TRPS II.
• These genes play significant roles in regulating gene activity, protein function, and cell division.

Gene mutations

• Researchers have determined that the loss of the EXT1 gene is responsible for the multiple osteochondromas seen in people with TRPS II.
• Loss of the TRPS1 gene is thought to cause the other bone and facial abnormalities.
• Deletion of the RAD21 gene may contribute to intellectual disability.
• The loss of other genes from this region of chromosome 8 likely contributes to the additional features of this condition.
• TRPS II is often described as a contiguous gene deletion syndrome because it results from the loss of several neighboring genes.
• A condition similar to TRPS II is caused by gene changes that affect only the TRPS1 gene.
• This condition, called trichorhinophalangeal syndrome type I (TRPS I), features similar bone, joint, skin, and facial characteristics as TRPS II.
• Individuals with TRPSI do not have osteochondromas or intellectual disability, which are not associated with the TRPS1 gene.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

• Most cases of TRPS II are not inherited, but occur as random events during the formation of reproductive cells (eggs or sperm) in a parent of an affected individual. These cases occur in people with no history of the disorder in their family. In a very small number of cases, people with TRPS II have inherited the chromosomal deletion from a parent with the condition.
• TRPS II is considered an autosomal dominant condition because one copy of the altered chromosome 8 in each cell is sufficient to cause the disorder.

Signs and symptoms

The condition is characterized by intellectual deficit and numerous other abnormalities including excess folds of skin, multiple bony growths (exostoses), characteristic facial features, and cone-shaped phalangeal epiphyses (the growing ends of the bones in the fingers).

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

• Bone pain
• Bulbous nose
• Cone-shaped epiphyses of the phalanges of the hand(Cone-shaped end part of finger bones)
• Deep philtrum
• Delayed skeletal maturation(Delayed bone maturation)
• Long philtrum
• Low-set, posteriorly rotated ears
• Multiple long-bone exostoses
• Protruding ear(Prominent ear)
• Short stature(Decreased body height)
• Sparse scalp hair(Reduced/lack of hair on scalp)
• Thin upper lip vermilion(Thin upper lip)

30%-79% of people have these symptoms

• Aplasia/Hypoplasia of the mandible
• Intellectual disability(Mental deficiency)
• Joint dislocation(Joint dislocations)
• Joint hyperflexibility(Joints move beyond expected range of motion)
• Redundant skin(Loose redundant skin)
• Thick eyebrow(Bushy eyebrows)

5%-29% of people have these symptoms

• Abnormal palate morphology(Abnormality of the palate)
• Abnormality of cardiovascular system morphology
• Avascular necrosis of the capital femoral epiphysis
• Bilateral single transverse palmar creases
• [[Brachydactyly](Short fingers or toes)
• Conductive hearing impairment(Conductive deafness)
• Genu valgum(Knock knees)
• Hip dysplasia
• Increased number of teeth(Extra teeth)
• Microcephaly(Abnormally small skull)
• Muscular hypotonia(Low or weak muscle tone)
• Recurrent urinary tract infections(Frequent urinary tract infections)
• Talipes
• Thick nasal alae
• Ventriculomegaly
• Vesicoureteral reflux
• Wide nasal bridge(Broad nasal bridge)

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 mainstay 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 2

Trichorhinophalangeal syndrome type 2 is a rare disease.

Trichorhinophalangeal syndrome type 2 Resources
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