Clinical Guidance

There is no clear genotype-phenotype correlation in TRPS I. However, missense variants have been reported to be associated with a more severe phenotype such as significant brachydactyly and severe short stature [, , , , ]. Phenotypic variability is also observed within and between families with the same TRPS1 pathogenic variant . The size of the minimal critical region responsible for the phenotypic features of TRPS II has been reported to be around 3 Mb . In TRPS II, no correlation was found between the size of the deleted segment and the severity of intellectual disability .

Source: GeneReviews — "Trichorhinophalangeal Syndrome"

Penetrance

No instances of reduced penetrance have been reported; thus, penetrance is believed to be 100% .

Source: GeneReviews — "Trichorhinophalangeal Syndrome"

Diagnostic Criteria

No consensus diagnostic criteria for trichorhinophalangeal syndrome (TRPS) have been published. TRPS includes TRPS I (caused by a heterozygous pathogenic variant in TRPS1) and TRPS II (caused by deletion of the contiguous genes TRPS1, RAD21, and EXT1).

Suggestive Findings

TRPS should be suspected in individuals with the following clinical, radiographic, and family history findings.

Clinical Findings

TRPS I and TRPS II

Source: GeneReviews — "Trichorhinophalangeal Syndrome"

Differential Diagnosis

Trichorhinophalangeal syndrome (TRPS) is often considered in the differential diagnosis of disorders with abnormalities of the hair, nose, and limbs .

Table 4.

Disorders of Interest in the Differential Diagnosis of Trichorhinophalangeal Syndrome

Gene/ Genetic Mechanism | Disorder | MOI | Features of Disorder:

Overlapping w/TRPS | Distinguishing from TRPS

DYNC2H1

DYNC2LI1

EVC

EVC2

GLI

PRKACA

PRKACB

SMO

WDR35

| Ellis-van Creveld syndrome | ARAD1 | • Short stature

• Brachydactyly

| • Nasal shape

• Oral frenula

• Polydactyly

EXT1

EXT2 | Hereditary multiple osteochondromas | AD | Multiple osteochondromas | • Absence of ID

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and support needs of an individual diagnosed with trichorhinophalangeal syndrome (TRPS), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 5.

Trichorhinophalangeal Syndrome: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Ectodermal

| Dental exam for supernumerary teeth |

Skeletal

| • Measurement of height

• Radiographs of hands, feet, pelvis, hips, if joint pain, swelling, /or limited mobility are present

| In those w/osteopenia on radiographs, further investigation for low bone mineral density may be warranted (e.g., DXA scan, serum calcium, phosphorus, magnesium, referral to endocrinologist for mgmt of bone health)

Assessment of osteochondromas by orthopedic specialist for evidence of functional limitation | In those w/TRPS II

Development

| Developmental assessment | In younger persons w/clinical diagnosis of TRPS (of unknown molecular cause) in all children w/TRPS II

Endocrinologic

| Eval for GH deficiency | In those w/short stature

Cardiac

| Cardiac eval incl echocardiogram | At diagnosis

Genetic counseling

| By genetics professionals1 | To inform affected persons their families re nature, MOI, implications of TRPS to facilitate medical personal decision making

DXA = dual-energy x-ray absorptiometry; GH = growth hormone; MOI = mode of inheritance; TRPS = trichorhinophalangeal syndrome

Source: GeneReviews — "Trichorhinophalangeal Syndrome"

Clinical Guidance

High-impact or contact sports may pose a risk to those with impaired mobility.

Source: GeneReviews — "Trichorhinophalangeal Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. To date, there are no therapies under investigation.

Source: GeneReviews — "Trichorhinophalangeal Syndrome"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended.

Table 7.

Trichorhinophalangeal Syndrome: Recommended Surveillance

System/Concern | Evaluation | Frequency

Skeletal

| • Monitor linear growth.

• Assess for joint manifestations.

| At each visit throughout childhood

Assess for frequent fractures. | At each visit

DXA scan | As needed in those w/suspected osteopenia

Radiographs of symptomatic osteochondromas | In those w/TRPS II when symptomatic at the end of puberty (when normal growth of osteochondromas has ceased) to provide a baseline for any future changes.

Development

| Developmental assessment | Annually throughout childhood in persons w/clinical diagnosis of TRPS (of unknown molecular cause) in all children w/TRPS II

DXA = dual-energy x-ray absorptiometry; TRPS = trichorhinophalangeal syndrome

Source: GeneReviews — "Trichorhinophalangeal Syndrome"