Diagnosis implications of the whole genome sequencing in a large Lebanese family with hyaline fibromatosis syndrome

Zahraa Haidar,Ramzi Temanni,Eliane Chouery,Nadine Jalkh,Francesco M Marincola,André Mégarbané,Lotfi Chouchane,Wassim Haidar,Soha Haddad,Wei Liu,Puthen Jithesh,Rashid Al-Ali,Ena Wang

doi:10.1186/s12863-017-0471-0

Abstract

BackgroundHyaline fibromatosis syndrome (HFS) is a recently introduced alternative term for two disorders that were previously known as juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH). These two variants are secondary to mutations in the anthrax toxin receptor 2 gene (ANTXR2) located on chromosome 4q21. The main clinical features of both entities include papular and/or nodular skin lesions, gingival hyperplasia, joint contractures and osteolytic bone lesions that appear in the first few years of life, and the syndrome typically progresses with the appearance of new lesions.MethodsWe describe five Lebanese patients from one family, aged between 28 and 58 years, and presenting with nodular and papular skin lesions, gingival hyperplasia, joint contractures and bone lesions. Because of the particular clinical features and the absence of a clinical diagnosis, Whole Genome Sequencing (WGS) was carried out on DNA samples from the proband and his parents.ResultsA mutation in ANTXR2 (p. Gly116Val) that yielded a diagnosis of HFS was noted.ConclusionsThe main goal of this paper is to add to the knowledge related to the clinical and radiographic aspects of HFS in adulthood and to show the importance of Next-Generation Sequencing (NGS) techniques in resolving such puzzling cases.

Highlights

Hyaline fibromatosis syndrome (HFS) is a recently introduced alternative term for two disorders that were previously known as juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH)
The anthrax toxin receptor 2 gene (ANTXR2) mutation results in a substitution of glycine by valine, and the zinc finger protein 618 (ZNF618) mutation leads to a premature stop codon
Here, we report five adult patients from a consanguineous Lebanese family, who presented with nodular skin lesions, gingival hyperplasia, joint contractures and bone lesions

Summary

Introduction

Hyaline fibromatosis syndrome (HFS) is a recently introduced alternative term for two disorders that were previously known as juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH). Juvenile hyaline fibromatosis (JHF, OMIM # 228600) is a rare inherited autosomal recessive disorder [1] that was first described by McMurray as Molluscom fibrosum [2] It is characterized by skin lesions (nodules and/or pearly papules); gingival hyperplasia; joint contracture; abnormal growth of hyalinized fibrous tissues of the head, neck and extremities; and bone lesions [3]. Infantile systemic hyalinosis (ISH, OMIM # 236490), another rarer disorder, shares many similarities with JHF [9, 10] It is characterized by a more severe presentation than JHF and has an early onset (first weeks or months of life) and symptoms that include failure to thrive, short stature, diffuse thickening of the skin, hyperpigmented plaques over the joints, visceral involvement, persistent diarrhea and recurrent infections, and death usually occurs within the first 2 years of life [11,12,13]

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