Genetic determinants of syndactyly: perspectives on pathogenesis and diagnosis

The formation of the digits is a tightly regulated process. During embryogenesis, disturbance of genetic pathways in limb development could result in syndactyly; a common congenital malformation consisting of webbing in adjacent digits. Currently, there is a paucity of knowledge regarding the exact...

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Published in:Orphanet journal of rare diseases 2022-05, Vol.17 (1), p.198-198, Article 198
Main Authors: Cassim, Afraah, Hettiarachchi, Dineshani, Dissanayake, Vajira H W
Format: Article
Language:English
Subjects:
Acids
Apoptosis
Bone growth
Bone morphogenetic proteins
Cartilage
Cell death
Congenital defects
Diagnosis
Embryogenesis
Fibroblast growth factor 8
Genes
Genetic screening
Ligands
Limb
Medical diagnosis
Medical research
Metabolites
Metalloproteinase
Pathogenesis
Proteins
Radiography
Rare diseases
Review
Syndactyly
Syndactyly classification
Synostosis
Wnt protein
WNT-BMP-FGF
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Summary:The formation of the digits is a tightly regulated process. During embryogenesis, disturbance of genetic pathways in limb development could result in syndactyly; a common congenital malformation consisting of webbing in adjacent digits. Currently, there is a paucity of knowledge regarding the exact developmental mechanism leading to this condition. The best studied canonical interactions of Wingless-type-Bone Morphogenic Protein-Fibroblast Growth Factor (WNT-BMP-FGF8), plays a role in the interdigital cell death (ICD) which is thought to be repressed in human syndactyly. Animal studies have displayed other pathways such as the Notch signaling, metalloprotease and non-canonical WNT-Planar cell polarity (PCP), to also contribute to failure of ICD, although less prominence has been given. The current diagnosis is based on a clinical evaluation followed by radiography when indicated, and surgical release of digits at 6 months of age is recommended. This review discusses the interactions repressing ICD in syndactyly, and characterizes genes associated with non-syndromic and selected syndromes involving syndactyly, according to the best studied canonical WNT-BMP-FGF interactions in humans. Additionally, the controversies regarding the current syndactyly classification and the effect of non-coding elements are evaluated, which to our knowledge has not been previously highlighted. The aim of the review is to better understand the developmental process leading to this condition.
ISSN:1750-1172
1750-1172
DOI:10.1186/s13023-022-02339-0