Recent Advances in Syndactyly: Basis, Current Status and Future Perspectives
Abstract
:1. Background
2. Classification of Syndactyly
3. Variable Phenotypic Features of Non-Syndromic Syndactyly Types
4. Genetic Factors Underlying the Differential Phenotypes of Syndactyly
5. Some Excluded Types of Syndactyly and Underlying Genetic Factors
6. HOXD13 and Its Role in Causing Syndactyly
Mutation Type | cDNA Change | AA Change | NCBI Ref. Sequence | Allele | Phenotype | Ref. |
---|---|---|---|---|---|---|
Missense | c.917G>A | p.R306Q | NM_000523.4 | Heterozygous | SD1-c | [13] |
Missense | c.500A>G | p.Y167C | NM_000523.4 | Heterozygous | SD1-b | [42] |
Missense | c.961A>C | p.T321P | NM_000523.4 | Heterozygous | SD1-c | [42] |
Missense | c.917G>A | p.R306Q | NM_000523.3 | Heterozygous | SD1-c | [43] |
Duplication | c.183_206dup | p.A64_A71dup | NM_000523.3 | Heterozygous | SPD1 | [82] |
Duplication | c.184_210dup | p.A63_A71dup | NM_000523.3 | Heterozygous | SPD1 | [80] |
Duplication | c.183_206dup | p.A64_A71dup | NM_000523.4 | Heterozygous | SPD1 | [90] |
Duplication | c.186-212dup | p.A63_A71dup | NM_000523.4 | Heterozygous | SPD1 | [91] |
Missense | c.859C>T | p.G287X | NM_000523.3 | Heterozygous | SPD1 | [83] |
Missense | c.556C>T | p.R186X | NM_000523.4 | Heterozygous | SPD1 | [84] |
Missense | c.938C>G | p.T313R | NM_000523.4 | Homozygous | SPD1 | [85] |
Missense | c.892C>T | p.R298W | NM_000523.2 | Heterozygous | SPD1 | [45] |
Missense | c.659G>T | p.G220V | NM_000523.2 | Heterozygous | SPD1 | [81] |
Missense | c.938C>G | p.T313R | NM_000523.3 | Homozygous | SPD1 | [86] |
Missense | c.893G>A | p.A298G | NM_000523.3 | Heterozygous | SPD1 | [44] |
Deletion | c.708delC | p.A236Lfs*30 | NM_000523.4 | Heterozygous | SPD1 | [92] |
Missense | c.925A>T | p.I309F | NM_000523.4 | Heterozygous | SPD1 | [88] |
Splice donor site | c.781+1G>A | - | NC_000002.12 NM_000523.3 | Heterozygous | SPD1 | [93] |
Missense | c.950A>G | p.Q317R | NM_000523.3 | Heterozygous | SD5 | [27] |
7. Diagnosis and Surgical Treatment of Syndactyly
8. Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Clinical Phenotype | Original Name | Major Symptoms | Locus/Gene | Mutation Type | Inheritance | References |
---|---|---|---|---|---|---|
Syndactyly I-a | Zygodactyly | Cutaneous webbing of 2nd and 3rd toes without the hand involvement | Chr.3p21.31 | - | AD* | [4,10,11] |
Syndactyly I-b | Lueken type | Bilateral bony or cutaneous webbing of 3rd/4th fingers and 2nd/3rd toes | HOXD13 | Duplication, missense, and deletion | AD | [4,12] |
Syndactyly I-c | Montagu type | Bilateral bony or cutaneous webbing of 3rd/4th fingers, with normal feet | HOXD13 | Duplication, missense, and deletion | AD | [4,13] |
Syndactyly I-d | Castilla type | Bilateral cutaneous webbing of the 4th and 5th toes | - | - | AD | [4,8,14] |
Syndactyly II-a | Vordingborg type | Distinct combinations of syndactyly and polydactyly | HOXD13 | Duplication, missense, frameshift, splicing and deletion | AD | [15,16,17] |
Syndactyly II-b | Metacarpal and metatarsal synostoses | FBLN1 | Missense | AD | [15,18] | |
Syndactyly II-c | Cutaneous webbing, abnormal metacarpals | Chr.14q11.2-12 | - | AD | [19] | |
Syndactyly III | Johnston-Kirby type | Bilateral complete syndactyly of the 4th and 5th fingers | Chr.7q36.3 | - | AD | [10,20,21] |
Syndactyly IV | Haas-type polysyndactyly | Complete cutaneous syndactyly of all fingers | LMBR1 | Large duplications and missense | AD | [22,23,24,25] |
Syndactyly V | Dowd type | Synostotic fusion of metacarpals | HOXD13 | Duplication, missense, and deletion | AD | [1,26,27] |
Syndactyly VI | Mitten type | Fusion of 2nd–5th fingers of the right hand | - | - | AD | [7] |
Syndactyly VII-a | Cenani-Lenz syndactyly (CLS) | Bony fusion of all digits | LRP4 | Missense | AR* | [28,29] |
Syndactyly VII-b | 15q13.3, GREM1-FMN1 | - | - | [30] | ||
Syndactyly VIII | Orel-Holmes type | Fusion of metacarpals 4/5 | FGF16 | Nonsense | XR* | [20] |
Syndactyly IX | Mesoaxial synostotic syndactyly (MSSD) | Phalangeal reduction | BHLHA9 | Missense, frameshift, and deletion | AR | [31,32,33] |
Gene | Deformity/Syndrome | References |
---|---|---|
APC | Cenani-Lenz syndrome and other related syndactyly disorders | [59] |
FIBULIN1 | Atrophy-syndactyly syndrome | [60] |
GLI3 | Acrocephalo-syndactyly | [62] |
GLI3 | Polydactyly and syndactyly | [63] |
GLI3 | Isolated postaxial synpolydactyly | [73] |
NSDH | CHILD syndrome phenotype and syndactyly | [64] |
TP63 | Syndactyly in combination with other abnormalities | [65,66] |
LRP4 | Isolated syndactyly | [70] |
GJA1 | Oculodentodigital dysplasia | [74] |
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Zaib, T.; Rashid, H.; Khan, H.; Zhou, X.; Sun, P. Recent Advances in Syndactyly: Basis, Current Status and Future Perspectives. Genes 2022, 13, 771. https://doi.org/10.3390/genes13050771
Zaib T, Rashid H, Khan H, Zhou X, Sun P. Recent Advances in Syndactyly: Basis, Current Status and Future Perspectives. Genes. 2022; 13(5):771. https://doi.org/10.3390/genes13050771
Chicago/Turabian StyleZaib, Tahir, Hibba Rashid, Hanif Khan, Xiaoling Zhou, and Pingnan Sun. 2022. "Recent Advances in Syndactyly: Basis, Current Status and Future Perspectives" Genes 13, no. 5: 771. https://doi.org/10.3390/genes13050771