Trichorhinophalangeal Syndrome

Excerpt

Clinical characteristics: Trichorhinophalangeal syndrome (TRPS) comprises TRPS I (caused by a heterozygous pathogenic variant in TRPS1) and TRPS II (caused by contiguous gene deletion of TRPS1, RAD21, and EXT1). Both types of TRPS are characterized by distinctive facial features; ectodermal features (fine, sparse, depigmented, and slow growing hair; dystrophic nails; and small breasts); and skeletal findings (short stature; short feet; brachydactyly with ulnar or radial deviation of the fingers; and early, marked hip dysplasia). TRPS II is characterized by multiple osteochondromas (typically first observed clinically on the scapulae and around the elbows and knees between ages 1 month and 6 years) and an increased risk of mild-to-moderate intellectual disability.

Diagnosis/testing: The diagnosis of TRPS is established in a proband with one of the following:

1. Typical clinical findings including facial features, ectodermal manifestations, and distal limb anomalies and radiographic findings of cone-shaped epiphyses

2. Suggestive findings of TRPS I and identification of a heterozygous pathogenic variant in TRPS1

3. Suggestive findings of TRPS II and a contiguous 8q23.3-q24.11 deletion that includes TRPS1, RAD21, and EXT1

Management: Treatment of manifestations: Management is principally supportive. 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.

Surveillance: For TRPS I and TRPS II: routine monitoring of linear growth and psychomotor developmental in childhood. For TRPS II only: x-ray evaluation of osteochondromas when symptomatic and at the end of puberty (when normal growth of osteochondromas has ceased) to provide a baseline for comparison with any future enlargement

Genetic counseling: TRPS is inherited in an autosomal dominant manner.

1. TRPS I. Many individuals with TRPS I have an affected parent; the exact proportion of TRPS I caused by a de novo pathogenic variant is unknown. Each child of an individual with TRPS I has a 50% chance of inheriting the TRPS1 pathogenic variant.

2. TRPS II. Most individuals with TRPS II have the disorder as the result of a de novo contiguous gene deletion of TRPS1, RAD21, and EXT1. Each child of an individual with TRPS II has a 50% chance of inheriting the contiguous gene deletion.

3. TRPS I and TRPS II. Once the genetic alteration causative of TRPS has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.