U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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
Clinical otosclerosis, the single most common cause of hearing impairment, is characterized by isolated endochondral bone sclerosis of the labyrinthine capsule. Otosclerotic foci invade the stapediovestibular joint (oval window) and interfere with free motion of the stapes. Mean age of onset is in the third decade and 90% of affected persons are under 50 years of age at the time of diagnosis. Approximately 10% of affected persons develop profound sensorineural hearing loss across all frequencies (summary by Tomek et al., 1998). Genetic Heterogeneity of Otosclerosis The locus associated with otosclerosis-1 (OTSC1) has been mapped to chromosome 15q26.1. Other loci associated with otosclerosis include OTSC2 (605727) on chromosome 7q; OTSC3 (608244) on chromosome 6p; OTSC4 (611571) on chromosome 16q; OTSC5 (608787) on chromosome 3q22-q24; OTSC7 (611572) on chromosome 6q13; OTSC8 (612096) on chromosome 9p13.1-q21.11; and OTSC10 (615589) on chromosome 1q41-q44. OTSC11 (620576) is caused by mutation in the FOXL1 gene (603252) on chromosome 16q24. OTSC12 (620792) is caused by mutation in the SMARCA4 gene (603254) on chromosome 19p13. The symbols OTSC6 and OTSC9 were reserved by the HUGO Gene Nomenclature Committee on January 30, 2003 and February 10, 2009, respectively, for as yet unpublished loci for otosclerosis.
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

Park DH, Yoon SH
World Neurosurg 2016 Aug;92:234-240. Epub 2016 May 10 doi: 10.1016/j.wneu.2016.05.004. PMID: 27178233
Passariello A, De Brasi D, Defferrari R, Genesio R, Tufano M, Mazzocco K, Capasso M, Migliorati R, Martinsson T, Siani P, Nitsch L, Tonini GP
Eur J Med Genet 2013 Nov;56(11):626-34. Epub 2013 Sep 13 doi: 10.1016/j.ejmg.2013.08.005. PMID: 24035971
Topouzelis N, Markovitsi E, Antoniades K
Cleft Palate Craniofac J 2003 Jul;40(4):433-6. doi: 10.1597/1545-1569_2003_040_0433_sscr_2.0.co_2. PMID: 12846610
Schaap C, Schrander-Stumpel CT, Fryns JP
Genet Couns 1992;3(4):209-15. PMID: 1472356
Askins G, Ger E
J Pediatr Orthop 1988 Jul-Aug;8(4):461-6. doi: 10.1097/01241398-198807000-00016. PMID: 2839541

Diagnosis

Miller KA, Twigg SR, McGowan SJ, Phipps JM, Fenwick AL, Johnson D, Wall SA, Noons P, Rees KE, Tidey EA, Craft J, Taylor J, Taylor JC, Goos JA, Swagemakers SM, Mathijssen IM, van der Spek PJ, Lord H, Lester T, Abid N, Cilliers D, Hurst JA, Morton JE, Sweeney E, Weber A, Wilson LC, Wilkie AO
J Med Genet 2017 Apr;54(4):260-268. Epub 2016 Nov 24 doi: 10.1136/jmedgenet-2016-104215. PMID: 27884935Free PMC Article
Bristol RE, Lekovic GP, Rekate HL
Semin Pediatr Neurol 2004 Dec;11(4):262-7. doi: 10.1016/j.spen.2004.11.001. PMID: 15828710
Hosalkar HS, Shah HS, Gujar PS, Shaw BA
J Postgrad Med 2001 Oct-Dec;47(4):252-5. PMID: 11832641
Chattopadhyay A, Kher AS, Udwadia AD, Sharma SV, Bharucha BA, Nicholson AD
J Postgrad Med 1993 Oct-Dec;39(4):228-30. PMID: 7996504
Visuthikosol V, Hompuem T
Ann Plast Surg 1988 Nov;21(5):489-95. doi: 10.1097/00000637-198811000-00017. PMID: 3232940

Therapy

Chaisrisawadisuk S, Taranath A, Azzopardi J, Moore MH
Childs Nerv Syst 2022 Apr;38(4):843-846. Epub 2021 Jul 10 doi: 10.1007/s00381-021-05285-7. PMID: 34247275
Fang Z, Zhao Z, Eapen V, Clarke RA
Genes (Basel) 2021 Aug 23;12(8) doi: 10.3390/genes12081290. PMID: 34440463Free PMC Article
Koh KL, Zain A
J Craniofac Surg 2018 Jun;29(4):861-867. doi: 10.1097/SCS.0000000000004347. PMID: 29438206
Boeckx W, Misani M, Vandermeeren L, Franck D, Zirak C, Demey A
J Reconstr Microsurg 2014 May;30(4):235-40. Epub 2014 Mar 28 doi: 10.1055/s-0033-1354735. PMID: 24683134
Amonoo-Kuofi K, Phillips SP, Randhawa PS, Lane R, Wyatt ME, Leighton SE
J Craniofac Surg 2009 Nov;20(6):1978-80. doi: 10.1097/SCS.0b013e3181bd2c9a. PMID: 19881386

Prognosis

Fukushima K, Parthasarathy P, Wade EM, Morgan T, Gowrishankar K, Markie DM, Robertson SP
Genes (Basel) 2021 Apr 5;12(4) doi: 10.3390/genes12040528. PMID: 33916386Free PMC Article
Dinçer T, Gümüş E, Toraman B, Er İ, Yildiz G, Yüksel Z, Kalay E
Am J Med Genet A 2021 Jun;185(6):1691-1699. Epub 2021 Mar 13 doi: 10.1002/ajmg.a.62154. PMID: 33713555
Miller KA, Twigg SR, McGowan SJ, Phipps JM, Fenwick AL, Johnson D, Wall SA, Noons P, Rees KE, Tidey EA, Craft J, Taylor J, Taylor JC, Goos JA, Swagemakers SM, Mathijssen IM, van der Spek PJ, Lord H, Lester T, Abid N, Cilliers D, Hurst JA, Morton JE, Sweeney E, Weber A, Wilson LC, Wilkie AO
J Med Genet 2017 Apr;54(4):260-268. Epub 2016 Nov 24 doi: 10.1136/jmedgenet-2016-104215. PMID: 27884935Free PMC Article
Schaap C, Schrander-Stumpel CT, Fryns JP
Genet Couns 1992;3(4):209-15. PMID: 1472356
Escobar LF, Bixler D, Sadove M, Bull MJ
Am J Med Genet 1988 Apr;29(4):829-36. doi: 10.1002/ajmg.1320290412. PMID: 3041834

Clinical prediction guides

Miller KA, Twigg SR, McGowan SJ, Phipps JM, Fenwick AL, Johnson D, Wall SA, Noons P, Rees KE, Tidey EA, Craft J, Taylor J, Taylor JC, Goos JA, Swagemakers SM, Mathijssen IM, van der Spek PJ, Lord H, Lester T, Abid N, Cilliers D, Hurst JA, Morton JE, Sweeney E, Weber A, Wilson LC, Wilkie AO
J Med Genet 2017 Apr;54(4):260-268. Epub 2016 Nov 24 doi: 10.1136/jmedgenet-2016-104215. PMID: 27884935Free 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
Kellermayer R
Genet Med 2006 Apr;8(4):213-6. doi: 10.1097/01.gim.0000214457.58378.1a. PMID: 16617241
Van Maldergem L, Verloes A, Lejeune L, Gillerot Y
J Med Genet 1992 Apr;29(4):266-8. doi: 10.1136/jmg.29.4.266. PMID: 1583650Free PMC Article
Ilyina HG, Lurie IW
Am J Med Genet 1990 Apr;35(4):561-5. doi: 10.1002/ajmg.1320350423. PMID: 2185633

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

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Consumer resources

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...