gms | German Medical Science

14th Triennial Congress of the International Federation of Societies for Surgery of the Hand (IFSSH), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT)

17.06. - 21.06.2019, Berlin

Pathologic Adipose Infiltration in Macrodactyly: The Mechanisms and Treatment Options

Meeting Abstract

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  • presenting/speaker Bin Wang - Shanghai 9th People's Hospital, Shanghai Jiaotong University, Shanghai, China

International Federation of Societies for Surgery of the Hand. International Federation of Societies for Hand Therapy. 14th Triennial Congress of the International Federation of Societies for Surgery of the Hand (IFSSH), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT). Berlin, 17.-21.06.2019. Düsseldorf: German Medical Science GMS Publishing House; 2020. DocIFSSH19-879

doi: 10.3205/19ifssh1373, urn:nbn:de:0183-19ifssh13731

Published: February 6, 2020

© 2020 Wang.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objectives/Interrogation: Macrodactyly is a rare congenital disease with manifestations invovling overgrowth of soft tissues and bones. The abnormal overgrowth with or without hyperostosis and nerve enlargement seriously affects the appearance and function of digits or limbs, which poses a great challenge for plastic and hand surgeons. Due to a lack of understanding of the molecular mechanism and pathological features of adipose invasion in the disease, there has been controversy regarding the surgical strategy and timing of debulking. The biological characteristics including the genomic profiles and cytological markers of Mac-ADSCs and fat infiltration of nerve tissue of the macrodactyly were investigated in the study.

Methods: Whole exome sequencing, Sanger sequencing, cDNA microarray and bioinformatics analysis were performed to identify mutations, gene expression patterns and signal transduction pathway changes in the pathological adipose tissues. The cellular characteristics of adipose-derived stem cells in macrodactyly (Mac-ADSCs) were studied using normal abdominal subcutaneous adipose-derived stem cells (Sat-ADSCs) as control, including features of cell cycle, apoptosis and differentiation induction of adipocytes, osteoblasts and cartilage. Electromyography (EMG) in patients with type II macrodactyly was examined, with the expression of neural proteins and ultrastructural changes evaluated.

Results and Conclusions: The PIK3CA-C420R and E81K mutations were identified in macrodactyly patients. The expression of EGFL6, ANGPTL7, PTN, FGF1, SFRP4 and other relevant genes was significantly up-regulated. Mac-ADSCs showed increased proliferative activity as well as osteogenesis and cartilage differentiation potential, while the adipogenic differentiation capability was decreased. Co-existence of myelin sheath injury, nerve regeneration and functional compensation was found in type II macrodactyly patients.Dysfunction of PI3K-AKT pathway activation which interferes with cell secretion and extracellular matrix - receptor interactions is an important mechanism for the development of macrodactyly, suggesting PI3K-AKT as a potenial target for medical intervention; The enhancement of osteogenesis and cartilage differentiation potential in Mac-ADSCs indicates that early defatting could potentially ameliorate the disease progression; The surgical decision to preserve or resect the enlarged nerve for type II macrodactyly patients should be determined according to the nerve injury and compensation situation of the digits.