Clinical Guidance

reported on genotype-phenotype correlations in 17 families:

• Those with at least one insertion/deletion in ANTXR2 resulting in a translational frameshift had a severe phenotype (infantile systemic hyalinosis).

• In-frame and missense variants in the cytoplasmic domain were associated with a milder phenotype, with survival to adulthood without recurrent infections, diarrhea, or multiorgan failure. Skeletal manifestations, however, were variably present.

A review of ANTXR2 variant type and disease grade was published by ; missense variants in the cytoplasmic domain were found to be less severe.

Source: GeneReviews — "Hyaline Fibromatosis Syndrome"

Diagnostic Criteria

No formal consensus clinical diagnostic criteria for hyaline fibromatosis syndrome (HFS) have been published; however, the clinical features below are highly suggestive of the condition.

Suggestive Findings

HFS should be suspected in probands with the following clinical, laboratory, histopathology, and radiographic features and family history. Clinical features are presented in order of their specificity for clinical diagnosis.

Clinical features

Source: GeneReviews — "Hyaline Fibromatosis Syndrome"

Differential Diagnosis

The conditions summarized in exhibit some features similar to hyaline fibromatosis syndrome (HFS); however, HFS can be distinguished by the characteristic associated pain, hyperpigmented skin lesions, and perianal and perioral masses.

Table 3.

Hyaline Fibromatosis Syndrome: Differential Diagnosis

Gene(s) | Disorder | MOI | Features of Disorder

Overlapping w/HFS | Differentiating from HFS

ASAH1

| Farber disease (See ASAH1-Related Disorders.) | AR | Typically presents w/painful joint contractures progressive hoarseness; skin nodules develop, esp over bony prominences | Neurologic involvement in most persons; absence of hyperpigmented patches

COL1A1

| Caffey disease (infantile cortical hyperostosis) | AD | Presents w/irritability, poor feeding, fever, soft tissue swelling | Characteristic radiographi...

Source: GeneReviews — "Hyaline Fibromatosis Syndrome"

Management Guidelines

No clinical practice guidelines for hyaline fibromatosis syndrome (HFS) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

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

Table 4.

Hyaline Fibromatosis Syndrome: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Skin | Assessment of skin involvement |

Musculoskeletal

| • Consider pain mgmt eval.

• Orthopedic rheumatologic eval in those w/contractures

| For contractures

GI/Nutrition

| Complete GI nutritional eval | Incl eval for intestinal malabsorption protein-losing enteropathy

Dental

| Consider dental eval. | To assess for gingival hypertrophy dental abnormalities

Endocrine

| Consider endocrine eval to assess bone health in those w/osteopenia on radiographs /or recurrent fractures. |

Immunologic

| Immunology eval, esp in those w/recurrent infections | To evaluate for immune deficiency, both cellular humoral, protein-losing enteropathy

Cardiac

| Consider echocardiogram. | To evaluate cardiac function

Genetic counseling

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

Source: GeneReviews — "Hyaline Fibromatosis 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. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Hyaline Fibromatosis 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 6. Hyaline Fibromatosis Syndrome: Recommended Surveillance

Source: GeneReviews — "Hyaline Fibromatosis Syndrome"