Trichorhinophalangeal Syndrome

Excerpt

Clinical characteristics: Trichorhinophalangeal syndrome (TRPS) comprises TRPS I (caused by a heterozygous pathogenic variant in TRPS1) and TRPS II (caused by a contiguous gene deletion of TRPS1, RAD21, and EXT1). Both TRPS types are characterized by distinctive facial features (large nose with broad nasal ridge and tip and underdeveloped alae; thick and broad medial eyebrows; long philtrum; thin vermilion of the upper lip; and large prominent ears); ectodermal features (fine, sparse, depigmented, and slow-growing hair and dystrophic nails); and skeletal findings (short stature, brachydactyly with ulnar or radial deviation of the fingers, short feet, and early, marked hip dysplasia). TRPS II is additionally characterized by multiple osteochondromas and an increased risk of mild-to-moderate intellectual disability.

Diagnosis/testing: The clinical diagnosis of TRPS can be established in a proband with characteristic facial features, ectodermal and joint manifestations, and skeletal findings of cone-shaped epiphyses. The molecular diagnosis of TRPS I is established in an individual with suggestive findings and identification of a heterozygous pathogenic variant in TRPS1; the molecular diagnosis of TRPS II is established in an individual with suggestive findings and a contiguous 8q23.3-q24.11 deletion that includes TRPS1, RAD21, and EXT1.

Management: Treatment of manifestations: Management of TRPS is principally supportive. Practical advice on hair care and use of wigs; consider extraction of supernumerary teeth; consider growth hormone (GH) therapy in those with short stature and GH deficiency; occupational therapy can benefit fine motor skills; analgesics (e.g., NSAIDs or other non-opiods) for joint pain; physiotherapy may relieve pain and aid mobility; encourage regular exercise; support with mobility at school and work as needed; consider prosthetic hip implantation in those with severe hip dysplasia; sunlight exposure, adequate dietary intake of calcium and vitamin D, and/or calcium and vitamin D supplementation; modify activities to prevent fractures; consider bisphosphonates in those with osteopenia; treatment of cardiac anomalies per cardiologist; peer support and psychological counseling if indicated. In those with TRPS II, consider resection of symptomatic osteochondromas; developmental and educational support.

Surveillance: Monitor linear growth and assess for joint manifestations at each visit throughout childhood; assess for frequent fractures at each visit; DXA scan as needed in those with suspected osteopenia. In those with TRPS II, radiographs of osteochondromas when symptomatic and at the end of puberty. In those with a clinical diagnosis of TRPS (of unknown molecular cause) and those with TRPS II, developmental assessment annually throughout childhood.

Agents/circumstances to avoid: High-impact or contact sports may pose a risk to those with impaired mobility.

Genetic counseling: TRPS is inherited in an autosomal dominant manner. Many individuals with TRPS I have an affected parent; about one third of affected individuals have the disorder as the result of a de novo pathogenic variant. Most individuals with TRPS II whose parents have undergone genetic testing have the disorder as the result of a de novo contiguous 8q23.3-q24.11 deletion. Each child of an individual with TRPS has a 50% chance of inheriting the TRPS-related genetic alteration. Once the TRPS-related genetic alteration has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.