Hyaline Fibromatosis Syndrome

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 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 including protein-losing enteropathy and inadequate weight gain can be life threatening. Cognitive development is normal. Some children with the severe form (also called infantile systemic hyalinosis) have a significant risk of morbidity or mortality in early childhood; some with a milder phenotype (also called juvenile hyaline fibromatosis) live well into adulthood with medical management.

DIAGNOSIS/TESTING: The diagnosis of HFS is established in a proband with characteristic clinical features and/or biallelic pathogenic variants in identified by molecular genetic testing. Skin biopsy may show hyaline material accumulation in the dermis or nondiagnostic findings; intestinal biopsy may demonstrate hyaline material, villous atrophy, and lymphangiectasia. Skeletal radiographs may show osteopenia, periosteal reaction, and lucent lesions.

MANAGEMENT

Treatment of skin nodules as recommended by dermatologist and/or plastic surgeon; perianal masses may be resected; physical therapy for joint contractures can be considered although pain may be problematic; nonsteroidal anti-inflammatory drugs, gabapentin, and/or potentially baclofen for pain; gentle handling; splinting may reduce pain; consultation with a pain management specialist; early consideration of 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; 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; treatment of dental anomalies per dentist and/or oral surgeon; treatment of osteopenia and fractures per endocrinologist and orthopedist; infections are treated based on the site of infection and causative agent; consider family support to manage chronic medical conditions. The following as needed based on clinical presentation: examination for concerning lesions; history and examination for contracture progression and pain; assessment of bone health; serum albumin; evaluation for gastrointestinal malabsorption; stool studies; nutrition assessment; examination for oral lesions that affect feeding/nutrition and dental complications; assessment of frequency of infections and antibody levels. Cardiac assessment as needed based on results of initial cardiac workup. Assessment of family needs at each visit.

GENETIC COUNSELING

HFS is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an 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. Once the pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.