Systemic Hyalinosis With Heterozygous CMG2 Mutations

Abstract

Juvenile hyaline fibromatosis (JHF) is a rare autosomal recessive disorder characterized by hyalinizing fibrosis of the skin and internal organs. Clinical features include multiple papular skin lesions, gingival hyperplasia, joint contractures, and osteolytic bone lesions. The systemic variant of JHF, known as infantile systemic hyalinosis (ISH), has an early onset and poor prognosis. Histological examination of cutaneous lesions shows bland-appearing fibroblasts within amorphous eosinophilic hyaline depositions. JHF and infantile systemic hyalinosis form a clinical spectrum with higher mortality that is typically observed in systemic cases. Here, the authors present a case of systemic hyalinosis with a heterozygous mutation in CMG2 that resulted in improved survival.

Síndrome de fibromatosis hialina: reporte de un caso y revisión bibliográfica

“…El Cuadro 2 muestra la comparación de los casos clínicos descritos en la bibliografía con síndrome de fibromatosis hialina infantil, incluido el nuestro, con los principales datos clínicos de los pacientes. [21][22][23][24][25][26][27] La movilidad articular en pacientes con síndrome de fibromatosis hialina suele mejorar con la administración de penicilamina, 1,2 antiinflamatorios no esteroides, opiáceos y gabapentina para el tratamiento del dolor, además de fisioterapia. Algunos casos requieren tratamiento paliativo.…”

Two novel mutations in the ANTXR2 gene in a Chinese patient suffering from hyaline fibromatosis syndrome: A case report

“…To the best of our knowledge, >40 pathogenic variants of ANTXR2 have been previously identified in the Human gene mutation database (http://www.hgmd.cf.ac.uk/). Of these reported variants, there are three common variants: c.1073-1074 insC, c.1073-1074 insCC and c.1074 delT (1,3,4,7,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). In the present study, a novel mutation at position c.1073 delC was revealed in the ANTXR2 gene.…”

“…The correlation between the genotype and phenotype of HFS has been previously investigated, and it may be suggested that the mutational spectrum may partially explain phenotypic variability (17). Previous studies have summarized previously reported HFS mutations and have provided a phenotype/grading system of patients with HFS (1,3,4,7,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). Patients with mutations occurring in the vWFA domain are classified as ISH/2-4 or JHF/2-3.…”

“…HFS is caused by either a homozygous or compound heterozygous mutation in the anthrax toxin receptor 2 (ANTXR2) gene, additionally termed the capillary morphogenesis protein 2 gene, which is localized on chromosome 4q21 (1,2). ANTXR2 encodes for a type I transmembrane (TM) protein, which consists of an extracellular N terminal von Willebrand A (vWA) domain, an immunoglobulin-like domain, a TM domain and a cytosolic tail (3)(4)(5)(6). TM is able to bind to laminin and collagen IV via its vWA domain, and thus may regulate basement membrane matrix assembly (7).…”

Gingival Hypertrophy in a Child with Hyaline Fibromatosis Syndrome

“…ANTXR2 was named after primarily being discovered as a receptor for the anthrax toxin of Bacillus anthracis. The pathogenesis of HFS has not been fully explained, but it seems that the mutation of the ANTXR2 causes the synthesis of a receptor that has impaired ability to interact with extracellular matrix components, leading to the accumulation of hyaline deposits in tissues (3). The first clinical signs may be present at birth or appear during infancy.…”