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Polysyndactyly 4(PPD4)

MedGen UID:
357420
Concept ID:
C1868111
Congenital Abnormality
Synonyms: Polysyndactyly uncomplicated; Preaxial polydactyly 4; Preaxial Polydactyly Type IV
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): GLI3 (7p14.1)
 
Monarch Initiative: MONDO:0008272
OMIM®: 174700
Orphanet: ORPHA93338

Definition

Although both preaxial polydactyly and syndactyly are cardinal features of this malformation, it is classified as a form of polydactyly because syndactyly does not occur in the absence of polydactyly (McClintic, 1935), the opposite not being true. On the other hand, polysyndactyly is here classified as a type of syndactyly because polydactyly (of the third or fourth fingers and fifth toes) does not occur in the absence of syndactyly. The thumb shows only the mildest degree of duplication, and syndactyly of various degrees affects fingers 3 and 4. The foot malformation is more constant and consists of duplication of part or all of the first or second toes and syndactyly affects all of the toes, especially the second and third. [from OMIM]

Clinical features

From HPO
Preaxial polydactyly
MedGen UID:
87498
Concept ID:
C0345354
Congenital Abnormality
A form of polydactyly in which the extra digit or digits are localized on the side of the thumb or great toe.
3-4 finger syndactyly
MedGen UID:
346463
Concept ID:
C1856889
Finding
Syndactyly with fusion of fingers three and four.
1-5 toe syndactyly
MedGen UID:
866880
Concept ID:
C4021235
Congenital Abnormality
Syndactyly with fusion of toes one to five (complete syndactyly of all toes of the foot).
Duplication of thumb phalanx
MedGen UID:
892306
Concept ID:
C4021370
Anatomical Abnormality
Complete or partial duplication of the phalanges of the thumb. Depending on the severity, the appearance on x-ray can vary from a notched phalanx (the duplicated bone is almost completely fused with the phalanx), a partially fused appearance of the two bones (bifid), two separate bones appearing side to side, or completely duplicated phalanges (proximal and distal phalanx of the thumb and/or 1st metacarpal). In contrast to the phalanges of the digits 2-5 (proximal, middle and distal), the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.
Dysplastic distal thumb phalanges with a central hole
MedGen UID:
870699
Concept ID:
C4025153
Anatomical Abnormality

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPolysyndactyly 4

Professional guidelines

PubMed

Salem J, Blumenow W, Markey A, Hogg ES, McCann E, Yassaie E, Hennedige A, De S, Sharma SD
J Craniofac Surg 2023 Oct 1;34(7):1985-1988. Epub 2023 Jul 21 doi: 10.1097/SCS.0000000000009541. PMID: 37477198
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Laryngoscope 2021 Apr;131(4):E1349-E1356. Epub 2020 Sep 4 doi: 10.1002/lary.29060. PMID: 32886384Free PMC Article
Yavropoulou MP, Xygonakis C, Lolou M, Karadimou F, Yovos JG
Hormones (Athens) 2014 Oct-Dec;13(4):323-37. doi: 10.14310/horm.2002.1552. PMID: 25555179

Recent clinical studies

Etiology

Kozin SH, Zlotolow DA
Plast Reconstr Surg 2015 Aug;136(2):241e-257e. doi: 10.1097/PRS.0000000000001499. PMID: 26218399
Rogers GF, Greene AK, Proctor MR, Mulliken JB, Goobie SM, Stoler JM
Cleft Palate Craniofac J 2015 Nov;52(6):751-7. Epub 2014 Oct 28 doi: 10.1597/14-092. PMID: 25350344
Biesecker LG
Orphanet J Rare Dis 2008 Apr 24;3:10. doi: 10.1186/1750-1172-3-10. PMID: 18435847Free PMC Article
Kotwal PP, Farooque M
J Bone Joint Surg Br 1998 Jul;80(4):651-3. doi: 10.1302/0301-620x.80b4.8489. PMID: 9699830
Cinalli G, Sainte-Rose C, Kollar EM, Zerah M, Brunelle F, Chumas P, Arnaud E, Marchac D, Pierre-Kahn A, Renier D
J Neurosurg 1998 Feb;88(2):209-14. doi: 10.3171/jns.1998.88.2.0209. PMID: 9452225

Diagnosis

Holmes LB, Nasri HZ
Am J Med Genet A 2022 Nov;188(11):3236-3241. Epub 2022 Sep 8 doi: 10.1002/ajmg.a.62941. PMID: 36073773
Buckwalter V JA, Shah AS
Hand (N Y) 2016 Dec;11(4):389-395. Epub 2016 Oct 10 doi: 10.1177/1558944716647355. PMID: 28149203Free PMC Article
Kozin SH, Zlotolow DA
Plast Reconstr Surg 2015 Aug;136(2):241e-257e. doi: 10.1097/PRS.0000000000001499. PMID: 26218399
Rogers GF, Greene AK, Proctor MR, Mulliken JB, Goobie SM, Stoler JM
Cleft Palate Craniofac J 2015 Nov;52(6):751-7. Epub 2014 Oct 28 doi: 10.1597/14-092. PMID: 25350344
Biesecker LG
Orphanet J Rare Dis 2008 Apr 24;3:10. doi: 10.1186/1750-1172-3-10. PMID: 18435847Free PMC Article

Therapy

Horiuchi S, Sato H, Iwasa A, Ichihara A, Tenshin H, Watanabe K, Hiasa M, Hashimoto I, Tanaka E
J Contemp Dent Pract 2021 Oct 1;22(10):1184-1190. PMID: 35197388
Claro F Jr, Sarian LO, Pinto-Neto AM
Ann Surg Oncol 2015 Aug;22(8):2540-50. Epub 2015 Jan 9 doi: 10.1245/s10434-014-4328-8. PMID: 25572679
Nahabedian MY
Plast Reconstr Surg 2011 Apr;127(4):91e-102e. doi: 10.1097/PRS.0b013e31820a7fa7. PMID: 21460647
Netscher DT, Baumholtz MA
Plast Reconstr Surg 2009 Nov;124(5):240e-252e. doi: 10.1097/PRS.0b013e3181b98c9c. PMID: 20009799
Taylor HO, Gellis SE, Schmidt BA, Upton J, Rogers GF
Ann Plast Surg 2008 Oct;61(4):472-6. doi: 10.1097/SAP.0b013e31816d8236. PMID: 18812724

Prognosis

Demetri LRF, Starcevich AG, Manske MCB, James MA
J Bone Joint Surg Am 2022 Jul 20;104(14):1301-1310. Epub 2022 Apr 14 doi: 10.2106/JBJS.21.01286. PMID: 35856931
Nazerani S, Nazerani T, Keramati MR
Tech Hand Up Extrem Surg 2022 Dec 1;26(4):276-281. doi: 10.1097/BTH.0000000000000399. PMID: 35698302
Kozin SH, Zlotolow DA
Plast Reconstr Surg 2015 Aug;136(2):241e-257e. doi: 10.1097/PRS.0000000000001499. PMID: 26218399
Biesecker LG
Orphanet J Rare Dis 2008 Apr 24;3:10. doi: 10.1186/1750-1172-3-10. PMID: 18435847Free PMC Article
Kotwal PP, Farooque M
J Bone Joint Surg Br 1998 Jul;80(4):651-3. doi: 10.1302/0301-620x.80b4.8489. PMID: 9699830

Clinical prediction guides

Nor AM, Jagdeesh K, Mohd FAS, Kamraul AK, Yusmadi A, Noraslawati R, Malina O, Roziana R
Med J Malaysia 2023 Nov;78(6):756-762. PMID: 38031217
Ishigaki T, Akita S, Suzuki H, Udagawa A, Mitsukawa N
J Plast Reconstr Aesthet Surg 2019 Jul;72(7):1170-1177. Epub 2019 Mar 2 doi: 10.1016/j.bjps.2019.02.030. PMID: 30898504
Gore AI, Spencer JP
Am Fam Physician 2004 Feb 15;69(4):865-72. PMID: 14989573
Frydman M, Katz M, Cabot SG, Soen G, Kauschansky A, Sirota L
Am J Med Genet 1997 Aug 22;71(3):251-7. doi: 10.1002/(sici)1096-8628(19970822)71:3<251::aid-ajmg1>3.0.co;2-x. PMID: 9268091
Ogino T
Hand Clin 1990 Nov;6(4):661-71. PMID: 2176655

Recent systematic reviews

Meyers A, Bassiri Gharb B, Rampazzo A
Plast Reconstr Surg 2023 Jun 1;151(6):1256-1273. Epub 2022 Dec 26 doi: 10.1097/PRS.0000000000010116. PMID: 36728793
Homans JF, Tromp IN, Colo D, Schlösser TPC, Kruyt MC, Deeney VFX, Crowley TB, McDonald-McGinn DM, Castelein RM
Am J Med Genet A 2018 Oct;176(10):2104-2120. Epub 2017 Nov 21 doi: 10.1002/ajmg.a.38545. PMID: 29159873
Claro F Jr, Sarian LO, Pinto-Neto AM
Ann Surg Oncol 2015 Aug;22(8):2540-50. Epub 2015 Jan 9 doi: 10.1245/s10434-014-4328-8. PMID: 25572679

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