Clinical Guidance

No genotype-phenotype correlations have been observed. Mild variation in age of onset, severity, and progression noted in different families is not explained by the type of pathogenic variants or their locations. Intrafamilial variation has been observed .

Source: GeneReviews — "Progressive Pseudorheumatoid Dysplasia"

Diagnostic Criteria

No consensus clinical diagnostic criteria for progressive pseudorheumatoid dysplasia (PPD) have been published.

Suggestive Findings

PPD should be suspected in individuals with the following clinical, laboratory, and radiologic features.

Clinical features

• Healthy at birth

• Onset of arthropathy early in childhood, usually between ages three and six years

• Enlargement of interphalangeal joints of hands

• Progressive restricted mobility of all joints

• Gait abnormalities

• Genu valgum / genu varum

• Progressive hip disease (commonly coxa vara at the late stage)

• Articular pain

• Motor weakness and fatigability

• Spine involvement in late childhood and adolescence with thoracolumbar kyphoscoliosis that leads to short trunk

• Adult height below the third centile

• Absence of signs of inflammation

Source: GeneReviews — "Progressive Pseudorheumatoid Dysplasia"

Differential Diagnosis

Juvenile idiopathic arthritis and all skeletal dysplasias with epiphyseal and spondylar involvement are to be considered in the differential diagnosis of progressive pseudorheumatoid dysplasia (PPD). Juvenile idiopathic arthritis (JIA) is the disorder most commonly confused with PPD. The main differentiating features are: • Joint inflammation (tenderness and warmth) in JIA • Elevation of erythrocyte sedimentation rate and C-reactive protein levels in JIA and not in PPD. However, in some instances elevation of these acute reactants in JIA can be minimal. • In JIA, joint destruction is seen on radiographs. In PPD, radiographs show dysplasia along with epiphyseal enlargement and platyspondyly. Skeletal dysplasias with epiphyseal and spondylar involvement. See . Table 3. Genes of Interest in the Differential Diagnosis of Progressive Pseudorheumatoid Dysplasia

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with progressive pseudorheumatoid dysplasia (PPD), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 4.

Recommended Evaluations Following Initial Diagnosis in Individuals with Progressive Pseudorheumatoid Dysplasia

System/Concern | Evaluation | Comment

Skeletal

|

• Complete skeletal survey

• Referral to pediatric orthopedic surgeon or specialist in treating bone dysplasias

|

Genetic

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

MOI = mode of inheritance; PPD = progressive pseudorheumatoid dysplasia

1. Medical geneticist, certified genetic counselor, or certified advanced genetic nurse

Treatment of Manifestations

Treatment is supportive. No specific therapy for PPD is available.

Table 5.

Treatment of Manifestations in Individuals with Progressive Pseudorheumatoid Dysplasia

Manifestation/Concern | Treatment | Considerations/Other

Pain due to secondary

osteoarthritis | NSAIDs may be helpful. | Other anti-inflammatory medications incl steroids immunosuppressive drugs (cyclosporine methotrexate) have a limited role in treatment are best avoided in view of their significant side effects.

Source: GeneReviews — "Progressive Pseudorheumatoid Dysplasia"

Clinical Guidance

Avoid immobilization (e.g., casting).

Source: GeneReviews — "Progressive Pseudorheumatoid Dysplasia"

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. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Progressive Pseudorheumatoid Dysplasia"

Surveillance Guidelines

No specific guidelines for surveillance have been published.

Table 6.

Recommended Surveillance for Individuals with Progressive Pseudorheumatoid Dysplasia

System/Concern | Evaluation | Frequency

Skeletal

| Monitor for orthopedic complications incl bone deformity, secondary joint disease, spinal deformities, pain. | At each visit

Eval by specialist in skeletal dysplasia or multidisciplinary skeletal dysplasia clinic | Annually

Source: GeneReviews — "Progressive Pseudorheumatoid Dysplasia"