The molecular genetics of human appendicular skeleton

Mol Genet Genomics. 2022 Sep;297(5):1195-1214. doi: 10.1007/s00438-022-01930-1. Epub 2022 Jul 30.


Disorders that result from de-arrangement of growth, development and/or differentiation of the appendages (limbs and digit) are collectively called as inherited abnormalities of human appendicular skeleton. The bones of appendicular skeleton have central role in locomotion and movement. The different types of appendicular skeletal abnormalities are well described in the report of "Nosology and Classification of Genetic skeletal disorders: 2019 Revision". In the current article, we intend to present the embryology, developmental pathways, disorders and the molecular genetics of the appendicular skeletal malformations. We mainly focused on the polydactyly, syndactyly, brachydactyly, split-hand-foot malformation and clubfoot disorders. To our knowledge, only nine genes of polydactyly, five genes of split-hand-foot malformation, nine genes for syndactyly, eight genes for brachydactyly and only single gene for clubfoot have been identified to be involved in disease pathophysiology. The current molecular genetic data will help life sciences researchers working on the rare skeletal disorders. Moreover, the aim of present systematic review is to gather the published knowledge on molecular genetics of appendicular skeleton, which would help in genetic counseling and molecular diagnosis.

Keywords: Appendicular skeleton; Databases; Molecular genetics; Mutations; Skeleton pathways.

Publication types

  • Systematic Review

MeSH terms

  • Brachydactyly / enzymology
  • Brachydactyly / genetics
  • Clubfoot / embryology
  • Clubfoot / genetics
  • Humans
  • Limb Deformities, Congenital* / diagnosis
  • Limb Deformities, Congenital* / embryology
  • Limb Deformities, Congenital* / genetics
  • Molecular Biology
  • Polydactyly / embryology
  • Polydactyly / genetics
  • Syndactyly / embryology
  • Syndactyly / genetics

Supplementary concepts

  • Split hand foot deformity