Hyaline Fibromatosis Syndrome: Early Outcomes Following Major Craniofacial Mass Excision.

Hyaline fibromatosis syndrome (HFS) is a rare congenital disorder characterized by abnormal hyaline deposition within soft tissues. Hyaline fibromatosis syndrome manifests in 2 distinct forms: (1) infantile systemic hyalinosis and (2) juvenile hyaline fibromatosis. Infantile systemic hyalinosis, the more severe form, typically emerges in early childhood with extensive systemic involvement. In contrast, juvenile HFS is less severe, allowing patients to survive into adulthood. Common clinical manifestations include thickened skin, hyperpigmented patches, gingival hypertrophy, skin nodules, and progressive severe joint contractures, leading to significant morbidity and potential mortality. This case report describes a 7-year-old child who was diagnosed with HFS and presented with a very large, ulcerated, rapidly expanding craniofacial mass. The patient underwent successful treatment involving a multidisciplinary medical team and strategic surgical intervention, achieving favorable postoperative outcomes.

Homozygosity for a Rare Plec Variant Suggests a Contributory Role in Congenital Insensitivity to Pain.

Congenital insensitivity to pain is a rare human condition in which affected individuals do not experience pain throughout their lives. This study aimed to identify the molecular etiology of congenital insensitivity to pain in two Thai patients. Clinical, radiographic, histopathologic, immunohistochemical, and molecular studies were performed. Patients were found to have congenital insensitivity to pain, self-mutilation, acro-osteolysis, cornea scars, reduced temperature sensation, tooth agenesis, root maldevelopment, and underdeveloped maxilla and mandible. The skin biopsies revealed fewer axons, decreased vimentin expression, and absent neurofilament expression, indicating lack of dermal nerves. Whole exome and Sanger sequencing identified a rare homozygous variant c.4039C>T; p.Arg1347Cys in the plakin domain of Plec, a cytolinker protein. This p.Arg1347Cys variant is in the spectrin repeat 9 region of the plakin domain, a region not previously found to harbor pathogenic missense variants in other plectinopathies. The substitution with a cysteine is expected to decrease the stability of the spectrin repeat 9 unit of the plakin domain. Whole mount in situ hybridization and an immunohistochemical study suggested that Plec is important for the development of maxilla and mandible, cornea, and distal phalanges. Additionally, the presence of dental anomalies in these patients further supports the potential involvement of Plec in tooth development. This is the first report showing the association between the Plec variant and congenital insensitivity to pain in humans.