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Multiple synostoses syndrome 4(SYNS4)

MedGen UID:
1638842
Concept ID:
C4693531
Disease or Syndrome
Synonyms: MULTIPLE SYNOSTOSES SYNDROME 4; SYNS4
 
Gene (location): GDF6 (8q22.1)
 
Monarch Initiative: MONDO:0054752
OMIM®: 617898

Definition

Multiple synostoses syndrome-4 is characterized by fusion of carpal and tarsal bones, as well as conductive hearing loss (Terhal et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of multiple synostoses syndrome, see SYNS1 (186500). [from OMIM]

Clinical features

From HPO
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Overlapping toe
MedGen UID:
182531
Concept ID:
C0920299
Anatomical Abnormality
Describes a foot digit resting on the dorsal surface of an adjacent digit when the foot is at rest. Initially clawing may be dynamic and only noticeable on walking. Over time the plantar plate tears, subluxation occurs at the metatarsophalangeal joint (MTPJ), and the deformity becomes permanent.
Broad foot
MedGen UID:
356187
Concept ID:
C1866241
Finding
A foot for which the measured width is above the 95th centile for age; or, a foot that appears disproportionately wide for its length.
Otosclerosis
MedGen UID:
10508
Concept ID:
C0029899
Disease or Syndrome
In otosclerosis, a callus of bone accumulates on the stapes creating a partial fixation. This limits the movement of the stapes bone, which results in hearing loss.
Tarsal synostosis
MedGen UID:
539393
Concept ID:
C0265654
Congenital Abnormality
Synostosis (bony fusion) involving one or more bones of the tarsus (calcaneus, talus, cuboid, navicular, cuneiiform bones).

Term Hierarchy

Professional guidelines

PubMed

Aruta G, Fiaschi P, Ceraudo M, Piatelli G, Capra V, Bianconi A, Rossi A, Secci F, Pavanello M
Pediatr Neurosurg 2023;58(2):67-79. Epub 2023 Jan 31 doi: 10.1159/000529129. PMID: 36720214
Potti TA, Petty EM, Lesperance MM
Hum Mutat 2011 Aug;32(8):877-86. Epub 2011 Jun 21 doi: 10.1002/humu.21515. PMID: 21538686
Watanabe K, Okada E, Kosaki K, Tsuji T, Ishii K, Nakamura M, Chiba K, Toyama Y, Matsumoto M
J Pediatr Orthop 2011 Mar;31(2):186-93. doi: 10.1097/BPO.0b013e3182093da5. PMID: 21307714

Recent clinical studies

Etiology

Yu T, Li G, Wang C, Li N, Yao R, Wang J
J Bone Miner Res 2023 Apr;38(4):568-577. Epub 2023 Feb 20 doi: 10.1002/jbmr.4785. PMID: 36744814
Polley JW, Figueroa AA, Girotto JA, Dietze-Fiedler ML
J Craniofac Surg 2022 Jan-Feb 01;33(1):270-275. doi: 10.1097/SCS.0000000000008111. PMID: 34967523
De Tienda M, Bouthors C, Pejin Z, Glorion C, Wicart P
J Pediatr Rehabil Med 2021;14(3):361-369. doi: 10.3233/PRM-200702. PMID: 34334433
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

Diagnosis

Xue AS, Buchanan EP, Hollier LH Jr
Plast Reconstr Surg 2022 Jun 1;149(6):1209e-1223e. Epub 2022 May 25 doi: 10.1097/PRS.0000000000009046. PMID: 35613293
Tahiri Y, Bartlett SP, Gilardino MS
Plast Reconstr Surg 2017 Jul;140(1):177e-191e. doi: 10.1097/PRS.0000000000003473. PMID: 28654618
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
Visuthikosol V, Hompuem T
Ann Plast Surg 1988 Nov;21(5):489-95. doi: 10.1097/00000637-198811000-00017. PMID: 3232940

Therapy

Fang Z, Zhao Z, Eapen V, Clarke RA
Genes (Basel) 2021 Aug 23;12(8) doi: 10.3390/genes12081290. PMID: 34440463Free PMC Article
Ford SE, Andersen JS, Macknet DM, Connor PM, Loeffler BJ, Gaston RG
J Shoulder Elbow Surg 2018 Oct;27(10):1898-1906. Epub 2018 Aug 20 doi: 10.1016/j.jse.2018.06.028. PMID: 30139681
Koh KL, Zain A
J Craniofac Surg 2018 Jun;29(4):861-867. doi: 10.1097/SCS.0000000000004347. PMID: 29438206
Nilsson D, Svensson J, Korkmaz BA, Nelvig H, Tisell M
J Neurosurg Pediatr 2013 Nov;12(5):483-90. Epub 2013 Sep 13 doi: 10.3171/2013.8.PEDS1370. PMID: 24032988
Allam KA, Wan DC, Khwanngern K, Kawamoto HK, Tanna N, Perry A, Bradley JP
Plast Reconstr Surg 2011 Apr;127(4):1601-1611. doi: 10.1097/PRS.0b013e31820a64b6. PMID: 21187805

Prognosis

Breik O, Mahindu A, Moore MH, Molloy CJ, Santoreneos S, David DJ
Childs Nerv Syst 2016 May;32(5):833-8. Epub 2016 Feb 10 doi: 10.1007/s00381-016-3036-z. PMID: 26861132
Miller WL
Sci Signal 2012 Oct 23;5(247):pt11. doi: 10.1126/scisignal.2003318. PMID: 23092891
Allam KA, Wan DC, Khwanngern K, Kawamoto HK, Tanna N, Perry A, Bradley JP
Plast Reconstr Surg 2011 Apr;127(4):1601-1611. doi: 10.1097/PRS.0b013e31820a64b6. PMID: 21187805
Biesecker LG
Orphanet J Rare Dis 2008 Apr 24;3:10. doi: 10.1186/1750-1172-3-10. PMID: 18435847Free PMC Article
Flores-Sarnat L
Semin Pediatr Neurol 2002 Dec;9(4):274-91. doi: 10.1053/spen.2002.32504. PMID: 12523552

Clinical prediction guides

Polley JW, Figueroa AA, Girotto JA, Dietze-Fiedler ML
J Craniofac Surg 2022 Jan-Feb 01;33(1):270-275. doi: 10.1097/SCS.0000000000008111. PMID: 34967523
Garrocho-Rangel A, Manriquez-Olmos L, Flores-Velazquez J, Rosales-Berber MA, Martinez-Rider R, Pozos-Guillen A
Med Oral Patol Oral Cir Bucal 2018 Jul 1;23(4):e421-e428. doi: 10.4317/medoral.22328. PMID: 29924758Free PMC Article
Flaherty K, Singh N, Richtsmeier JT
Wiley Interdiscip Rev Dev Biol 2016 Jul;5(4):429-59. Epub 2016 Mar 22 doi: 10.1002/wdev.227. PMID: 27002187Free PMC Article
Greig AV, Wagner J, Warren SM, Grayson B, McCarthy JG
J Craniofac Surg 2013 Jan;24(1):204-15. doi: 10.1097/SCS.0b013e31826704be. PMID: 23348287
Kellermayer R
Genet Med 2006 Apr;8(4):213-6. doi: 10.1097/01.gim.0000214457.58378.1a. PMID: 16617241

Recent systematic reviews

Richardson IJ, Wager LE, Recker MJ, Reynolds R, Ruiz R, Markiewicz MR
J Oral Maxillofac Surg 2022 Apr;80(4):651-661. Epub 2021 Nov 13 doi: 10.1016/j.joms.2021.10.022. PMID: 34863645
Saengthong P, Chaitusaney B, Hirunwiwatkul P, Charakorn N
Eur Arch Otorhinolaryngol 2019 Jun;276(6):1555-1560. Epub 2019 Apr 17 doi: 10.1007/s00405-019-05427-3. PMID: 30997567
Christian EA, Imahiyerobo TA, Nallapa S, Urata M, McComb JG, Krieger MD
Neurosurg Focus 2015 May;38(5):E6. doi: 10.3171/2015.2.FOCUS14853. PMID: 25929968

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