Hyaline fibromatosis syndrome: a rare, yet recognizable syndrome

Background. Hyaline fibromatosis syndrome is a rare autosomal recessive disorder caused by ANTXR2 pathogenic variants. The disorder is characterized by the deposition of amorphous hyaline material in connective tissues. The hallmarks of the disease are joint contractures, generalized skin stiffness...

Full description

Saved in:
Bibliographic Details
Main Authors: Tuğba Daşar, Hasibe Nesligül Gönen, Kemal Kösemehmetoğlu, Özlem Tekşam, Koray Boduroğlu, Gülen Eda Utine, Pelin Özlem Şimşek Kiper
Format: Article
Language:English
Published: Hacettepe University Institute of Child Health 2024-05-01
Series:The Turkish Journal of Pediatrics
Subjects:
Online Access:https://turkjpediatr.org/article/view/4511
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850240702614601728
author Tuğba Daşar
Hasibe Nesligül Gönen
Kemal Kösemehmetoğlu
Özlem Tekşam
Koray Boduroğlu
Gülen Eda Utine
Pelin Özlem Şimşek Kiper
author_facet Tuğba Daşar
Hasibe Nesligül Gönen
Kemal Kösemehmetoğlu
Özlem Tekşam
Koray Boduroğlu
Gülen Eda Utine
Pelin Özlem Şimşek Kiper
author_sort Tuğba Daşar
collection DOAJ
description Background. Hyaline fibromatosis syndrome is a rare autosomal recessive disorder caused by ANTXR2 pathogenic variants. The disorder is characterized by the deposition of amorphous hyaline material in connective tissues. The hallmarks of the disease are joint contractures, generalized skin stiffness, hyperpigmented papules over extensor surfaces of joints, fleshy perianal masses, severe diarrhea, and gingival hypertrophy. The severity of the disease varies and prognosis is poor. No specific treatment is yet available. Most patients with the severe form of the condition pass away before the second year of age. In this study, we describe the clinical and molecular findings of a cohort of seven hyaline fibromatosis syndrome patients who were diagnosed and followed up at a single tertiary reference center in Turkey. Methods. Genomic DNA was extracted by standard salting out method from peripheric blood samples of three patients. In one patient DNA extraction was performed on pathology slides since peripheric blood DNA was not available. All coding exons of the ANTXR2 were amplified and sequenced on ABI Prism 3500 Genetic Analyser. Results. Sanger sequencing was performed in 3 patients and homozygous c.945T>G p.(Cys315Trp), c.1073dup p.(Ala359CysfsTer13), and c.1074del p.(Ala359HisfsTer50) variants were identified in ANTXR2. All patients passed away before the age of five years. Conclusions. HFS is a rare, progressive disorder with a broad phenotypic spectrum. HFS can be recognized easily with distinctive clinical features. Nevertheless, it has poor prognosis with increased mortality due to severe clinical decompensation.
format Article
id doaj-art-e33280b04c0f489aa5adfb5df0ec396d
institution OA Journals
issn 0041-4301
2791-6421
language English
publishDate 2024-05-01
publisher Hacettepe University Institute of Child Health
record_format Article
series The Turkish Journal of Pediatrics
spelling doaj-art-e33280b04c0f489aa5adfb5df0ec396d2025-08-20T02:00:47ZengHacettepe University Institute of Child HealthThe Turkish Journal of Pediatrics0041-43012791-64212024-05-0166210.24953/turkjpediatr.2024.4511Hyaline fibromatosis syndrome: a rare, yet recognizable syndromeTuğba Daşar0https://orcid.org/0000-0002-1493-4352Hasibe Nesligül Gönen1https://orcid.org/0000-0001-6903-5779Kemal Kösemehmetoğlu2https://orcid.org/0000-0002-7747-0460Özlem Tekşam3https://orcid.org/0000-0003-1856-0500Koray Boduroğlu4https://orcid.org/0000-0001-6260-1942Gülen Eda Utine5https://orcid.org/0000-0001-6577-5542Pelin Özlem Şimşek Kiper6https://orcid.org/0000-0001-7244-7766Division of Pediatric Genetics, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, TürkiyeDepartment of Medical Genetics, Faculty of Medicine, Hacettepe University, Ankara, TürkiyeDepartment of Pathology, Faculty of Medicine, Hacettepe University, Ankara, TürkiyeDepartment of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, TürkiyeDivision of Pediatric Genetics, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, TürkiyeDivision of Pediatric Genetics, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, TürkiyeDivision of Pediatric Genetics, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Türkiye Background. Hyaline fibromatosis syndrome is a rare autosomal recessive disorder caused by ANTXR2 pathogenic variants. The disorder is characterized by the deposition of amorphous hyaline material in connective tissues. The hallmarks of the disease are joint contractures, generalized skin stiffness, hyperpigmented papules over extensor surfaces of joints, fleshy perianal masses, severe diarrhea, and gingival hypertrophy. The severity of the disease varies and prognosis is poor. No specific treatment is yet available. Most patients with the severe form of the condition pass away before the second year of age. In this study, we describe the clinical and molecular findings of a cohort of seven hyaline fibromatosis syndrome patients who were diagnosed and followed up at a single tertiary reference center in Turkey. Methods. Genomic DNA was extracted by standard salting out method from peripheric blood samples of three patients. In one patient DNA extraction was performed on pathology slides since peripheric blood DNA was not available. All coding exons of the ANTXR2 were amplified and sequenced on ABI Prism 3500 Genetic Analyser. Results. Sanger sequencing was performed in 3 patients and homozygous c.945T>G p.(Cys315Trp), c.1073dup p.(Ala359CysfsTer13), and c.1074del p.(Ala359HisfsTer50) variants were identified in ANTXR2. All patients passed away before the age of five years. Conclusions. HFS is a rare, progressive disorder with a broad phenotypic spectrum. HFS can be recognized easily with distinctive clinical features. Nevertheless, it has poor prognosis with increased mortality due to severe clinical decompensation. https://turkjpediatr.org/article/view/4511Hyaline Fibromatosis Syndromejuvenile hyaline fibromatosisinfantile systemic hyalinosisANTXR2CMG2
spellingShingle Tuğba Daşar
Hasibe Nesligül Gönen
Kemal Kösemehmetoğlu
Özlem Tekşam
Koray Boduroğlu
Gülen Eda Utine
Pelin Özlem Şimşek Kiper
Hyaline fibromatosis syndrome: a rare, yet recognizable syndrome
The Turkish Journal of Pediatrics
Hyaline Fibromatosis Syndrome
juvenile hyaline fibromatosis
infantile systemic hyalinosis
ANTXR2
CMG2
title Hyaline fibromatosis syndrome: a rare, yet recognizable syndrome
title_full Hyaline fibromatosis syndrome: a rare, yet recognizable syndrome
title_fullStr Hyaline fibromatosis syndrome: a rare, yet recognizable syndrome
title_full_unstemmed Hyaline fibromatosis syndrome: a rare, yet recognizable syndrome
title_short Hyaline fibromatosis syndrome: a rare, yet recognizable syndrome
title_sort hyaline fibromatosis syndrome a rare yet recognizable syndrome
topic Hyaline Fibromatosis Syndrome
juvenile hyaline fibromatosis
infantile systemic hyalinosis
ANTXR2
CMG2
url https://turkjpediatr.org/article/view/4511
work_keys_str_mv AT tugbadasar hyalinefibromatosissyndromearareyetrecognizablesyndrome
AT hasibenesligulgonen hyalinefibromatosissyndromearareyetrecognizablesyndrome
AT kemalkosemehmetoglu hyalinefibromatosissyndromearareyetrecognizablesyndrome
AT ozlemteksam hyalinefibromatosissyndromearareyetrecognizablesyndrome
AT korayboduroglu hyalinefibromatosissyndromearareyetrecognizablesyndrome
AT gulenedautine hyalinefibromatosissyndromearareyetrecognizablesyndrome
AT pelinozlemsimsekkiper hyalinefibromatosissyndromearareyetrecognizablesyndrome