Hyaline Fibromatosis Syndrome

Excerpt

Clinical characteristics: Hyaline fibromatosis syndrome (HFS) is characterized by hyaline deposits in the papillary dermis and other tissues. It can present at birth or in infancy with severe pain with movement, progressive joint contractures, and often with severe motor disability, thickened skin, and hyperpigmented macules/patches over bony prominences of the joints. Gingival hypertrophy, skin nodules, pearly papules of the face and neck, and perianal masses are common. Complications of protein-losing enteropathy and failure to thrive can be life threatening. Cognitive development is normal. Many children with the severe form (previously called infantile systemic hyalinosis) have a significant risk of morbidity or mortality in early childhood; some with a milder phenotype (previously called juvenile hyaline fibromatosis) survive into adulthood.

Diagnosis/testing: The diagnosis of HFS is established in a proband with characteristic clinical features and/or biallelic pathogenic (or likely pathogenic) variants in ANTXR2 identified by molecular genetic testing. Skin biopsy may reveal hyaline material accumulation in the dermis or nondiagnostic findings; intestinal biopsy may demonstrate villous atrophy and lymphangiectasia. Skeletal x-rays may reveal osteopenia, periosteal reaction, and lucent lesions.

Management: Treatment of manifestations: Possible nasogastric tube, gastrostomy tube feeding, or parenteral nutrition under supervision of a gastroenterologist and nutritionist; nutrition tailored for the possibility of malabsorption or lymphangiectasia; hydration and albumin infusions for protein-losing enteropathy; physiotherapy for joint contractures can be considered although pain may be problematic; nonsteroidal anti-inflammatory drugs, opiates, and possibly gabapentin for pain; gentle handling; splinting may reduce pain; consultation with a pain management specialist as needed; lesions that obstruct the airway or interfere with feedings can be excised, but may recur; anesthesiologists need to be aware of potential difficulties with endotracheal intubation; perianal masses may be resected; treatment of skin nodules as recommended by dermatology and/or plastic surgery; infections are treated based on the site of infection and causative agent; consider family counseling to manage chronic medical condition.

Surveillance: The following as needed based on clinical presentation: antibody levels and serum albumin; evaluation for gastrointestinal malabsorption; nutrition assessment; history and examination for contracture progression and pain; examination for concerning lesions; examination for oral lesions that affect feeding/nutrition and dental complications; cardiac assessment.

Genetic counseling: HFS is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an ANTXR2 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being unaffected and a carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible once the ANTXR2 pathogenic variants have been identified in an affected family member.