KEGG DISEASE: Robinow syndrome

DISEASE: Robinow syndrome

Entry

H00485                      Disease

Name

Robinow syndrome

Description

Robinow syndrome (RS) is a rare genetically heterogeneous condition characterized by hypertelorism, nasal features (large nasal bridge, short upturned nose, and anteverted nares), midface hypoplasia, mesomelic limb shortening, brachydactyly, clinodactyly, micropenis, and short stature. Both autosomal recessive and autosomal dominant inheritance have been described. The phenotypic presentation in both types of RS overlaps; however, subtle variances in the severity of craniofacial, musculoskeletal, cardiovascular, and urogenital characteristics may be present. In general, autosomal recessive RS (RRS) patients have more severe dysmorphology than autosomal dominant RS (DRS), especially in the musculoskeletal system.

Category

Congenital malformation

Brite

Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
  Multiple developmental anomalies or syndromes
   LD24  Syndromes with skeletal anomalies as a major feature
    H00485  Robinow syndrome
Pathway-based classification of diseases [BR:br08402]
Signal transduction
  nt06505  WNT signaling
   H00485  Robinow syndrome

Pathway

hsa04310

Wnt signaling pathway

Network

nt06505 WNT signaling

Gene

(RRS1) ROR2 [HSA:4920] [KO:K05123]
(RRS2) NXN [HSA:64359] [KO:K17609]
(DRS1) WNT5A [HSA:7474] [KO:K00444]
(DRS2) DVL1 [HSA:1855] [KO:K02353]
(DRS3) DVL3 [HSA:1857] [KO:K02353]

Other DBs

ICD-11:

LD24.A

MeSH:

C562492 C535863

OMIM:

268310 180700 616331 616894 618529

Reference

PMID:19790289

Authors

Mundlos S

Title

The brachydactylies: a molecular disease family.

Journal

Clin Genet 76:123-36 (2009)
DOI:10.1111/j.1399-0004.2009.01238.x

Reference

PMID:12011143 (RRS1)

Authors

Patton MA, Afzal AR

Title

Robinow syndrome.

Journal

J Med Genet 39:305-10 (2002)
DOI:10.1136/jmg.39.5.305

Reference

PMID:20301418 (RRS1)

Authors

Bacino C

Title

ROR2-Related Robinow Syndrome

Journal

GeneReviews (1993)

Reference

PMID:21496006

Authors

Beiraghi S, Leon-Salazar V, Larson BE, John MT, Cunningham ML, Petryk A, Lohr JL

Title

Craniofacial and intraoral phenotype of Robinow syndrome forms.

Journal

Clin Genet 80:15-24 (2011)
DOI:10.1111/j.1399-0004.2011.01683.x

Reference

PMID:17256787

Authors

Mazzeu JF, Pardono E, Vianna-Morgante AM, Richieri-Costa A, Ae Kim C, Brunoni D, Martelli L, de Andrade CE, Colin G, Otto PA

Title

Clinical characterization of autosomal dominant and recessive variants of Robinow syndrome.

Journal

Am J Med Genet A 143:320-5 (2007)
DOI:10.1002/ajmg.a.31592

Reference

PMID:19918918 (DRS1)

Authors

Person AD, Beiraghi S, Sieben CM, Hermanson S, Neumann AN, Robu ME, Schleiffarth JR, Billington CJ Jr, van Bokhoven H, Hoogeboom JM, Mazzeu JF, Petryk A, Schimmenti LA, Brunner HG, Ekker SC, Lohr JL

Title

WNT5A mutations in patients with autosomal dominant Robinow syndrome.

Journal

Dev Dyn 239:327-37 (2010)
DOI:10.1002/dvdy.22156

Reference

PMID:25817016 (DRS2)

Authors

White J, Mazzeu JF, Hoischen A, Jhangiani SN, Gambin T, Alcino MC, Penney S, Saraiva JM, Hove H, Skovby F, Kayserili H, Estrella E, Vulto-van Silfhout AT, Steehouwer M, Muzny DM, Sutton VR, Gibbs RA, Lupski JR, Brunner HG, van Bon BW, Carvalho CM

Title

DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome.

Journal

Am J Hum Genet 96:612-22 (2015)
DOI:10.1016/j.ajhg.2015.02.015

Reference

PMID:26924530 (DRS3)

Authors

White JJ, Mazzeu JF, Hoischen A, Bayram Y, Withers M, Gezdirici A, Kimonis V, Steehouwer M, Jhangiani SN, Muzny DM, Gibbs RA, van Bon BW, Sutton VR, Lupski JR, Brunner HG, Carvalho CM

Title

DVL3 Alleles Resulting in a -1 Frameshift of the Last Exon Mediate Autosomal-Dominant Robinow Syndrome.

Journal

Am J Hum Genet 98:553-61 (2016)
DOI:10.1016/j.ajhg.2016.01.005

Reference

PMID:29276006 (RRS1/2, DRS1/2/3)

Authors

White JJ, Mazzeu JF, Coban-Akdemir Z, Bayram Y, Bahrambeigi V, Hoischen A, van Bon BWM, Gezdirici A, Gulec EY, Ramond F, Touraine R, Thevenon J, Shinawi M, Beaver E, Heeley J, Hoover-Fong J, Durmaz CD, Karabulut HG, Marzioglu-Ozdemir E, Cayir A, Duz MB, Seven M, Price S, Ferreira BM, Vianna-Morgante AM, Ellard S, Parrish A, Stals K, Flores-Daboub J, Jhangiani SN, Gibbs RA, Brunner HG, Sutton VR, Lupski JR, Carvalho CMB

Title

WNT Signaling Perturbations Underlie the Genetic Heterogeneity of Robinow Syndrome.

Journal

Am J Hum Genet 102:27-43 (2018)
DOI:10.1016/j.ajhg.2017.10.002

LinkDB

» Japanese version

DISEASE: Brachydactyly

Entry

H00482                      Disease

Name

Brachydactyly

Subgroup

Brachydactyly type A (BDA)
Brachydactyly type B (BDB)
Brachydactyly type C (BDC)
Brachydactyly type D (BDD)
Brachydactyly type E (BDE)
Hypertension and brachydactyly syndrome (HTNB)

Description

Brachydactyly (BD) comprises hereditary limb malformations characterized by apparent shortening of digits. Bone dysostosis is seen in middle phalanges in type A; distal phalanges in type B; distal phalanx of the thumb in type D; metacarpals in type E. Type C is characterized by shortening of multiple phalanges and hyperphalangy. BD is caused by improper development of the bones.

Category

Congenital malformation

Brite

Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
  Structural developmental anomalies primarily affecting one body system
   Structural developmental anomalies of the skeleton
    LB75  Brachydactyly
     H00482  Brachydactyly
Pathway-based classification of diseases [BR:br08402]
Signal transduction
  nt06505  WNT signaling
   H00482  Brachydactyly
  nt06501  HH signaling
   H00482  Brachydactyly
  nt06507  TGFB signaling
   H00482  Brachydactyly

Pathway

hsa04350

TGF-beta signaling pathway

hsa04340

Hedgehog signaling pathway

Network

nt06501 HH signaling
nt06505 WNT signaling
nt06507 TGFB signaling

Gene

(BDA1) IHH [HSA:3549] [KO:K11989]
(BDA1C, BDA2, BDC) GDF5 [HSA:8200] [KO:K04664]
(BDA1D, BDA2) BMPR1B [HSA:658] [KO:K13578]
(BDA2) BMP2 [HSA:650] [KO:K21283]
(BDB1) ROR2 [HSA:4920] [KO:K05123]
(BDB2) NOG [HSA:9241] [KO:K04658]
(BDD, BDE1) HOXD13 [HSA:3239] [KO:K09298]
(BDE2) PTHLH [HSA:5744] [KO:K22608]
(HTNB) PDE3A [HSA:5139] [KO:K19021]

Other DBs

ICD-11:

LB75

MeSH:

D059327

OMIM:

112500 615072 616849 112600 113000 611377 113100 113200 113300 613382 112410

Reference

PMID:19790289

Authors

Mundlos S

Title

The brachydactylies: a molecular disease family.

Journal

Clin Genet 76:123-36 (2009)
DOI:10.1111/j.1399-0004.2009.01238.x

Reference

PMID:18554391

Authors

Temtamy SA, Aglan MS

Title

Brachydactyly.

Journal

Orphanet J Rare Dis 3:15 (2008)
DOI:10.1186/1750-1172-3-15

Reference

PMID:11455389 (IHH)

Authors

Gao B, Guo J, She C, Shu A, Yang M, Tan Z, Yang X, Guo S, Feng G, He L

Title

Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-1.

Journal

Nat Genet 28:386-8 (2001)
DOI:10.1038/ng577

Reference

PMID:20683927 (GDF5, BDA1C)

Authors

Byrnes AM, Racacho L, Nikkel SM, Xiao F, MacDonald H, Underhill TM, Bulman DE

Title

Mutations in GDF5 presenting as semidominant brachydactyly A1.

Journal

Hum Mutat 31:1155-62 (2010)
DOI:10.1002/humu.21338

Reference

PMID:16127465 (GDF5, BDA2)

Authors

Seemann P, Schwappacher R, Kjaer KW, Krakow D, Lehmann K, Dawson K, Stricker S, Pohl J, Ploger F, Staub E, Nickel J, Sebald W, Knaus P, Mundlos S

Title

Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2.

Journal

J Clin Invest 115:2373-81 (2005)
DOI:10.1172/JCI25118

Reference

PMID:9288091 (GDF5, BDC)

Authors

Polinkovsky A, Robin NH, Thomas JT, Irons M, Lynn A, Goodman FR, Reardon W, Kant SG, Brunner HG, van der Burgt I, Chitayat D, McGaughran J, Donnai D, Luyten FP, Warman ML

Title

Mutations in CDMP1 cause autosomal dominant brachydactyly type C.

Journal

Nat Genet 17:18-9 (1997)
DOI:10.1038/ng0997-18

Reference

PMID:25758993 (BMPR1B, BDA1D)

Authors

Racacho L, Byrnes AM, MacDonald H, Dranse HJ, Nikkel SM, Allanson J, Rosser E, Underhill TM, Bulman DE

Title

Two novel disease-causing variants in BMPR1B are associated with brachydactyly type A1.

Journal

Eur J Hum Genet 23:1640-5 (2015)
DOI:10.1038/ejhg.2015.38

Reference

PMID:14523231 (BMPR1B, BDA2)

Authors

Lehmann K, Seemann P, Stricker S, Sammar M, Meyer B, Suring K, Majewski F, Tinschert S, Grzeschik KH, Muller D, Knaus P, Nurnberg P, Mundlos S

Title

Mutations in bone morphogenetic protein receptor 1B cause brachydactyly type A2.

Journal

Proc Natl Acad Sci U S A 100:12277-82 (2003)
DOI:10.1073/pnas.2133476100

Reference

PMID:19327734 (BMP2)

Authors

Dathe K, Kjaer KW, Brehm A, Meinecke P, Nurnberg P, Neto JC, Brunoni D, Tommerup N, Ott CE, Klopocki E, Seemann P, Mundlos S

Title

Duplications involving a conserved regulatory element downstream of BMP2 are associated with brachydactyly type A2.

Journal

Am J Hum Genet 84:483-92 (2009)
DOI:10.1016/j.ajhg.2009.03.001

Reference

PMID:10700182 (ROR2)

Authors

Oldridge M, Fortuna AM, Maringa M, Propping P, Mansour S, Pollitt C, DeChiara TM, Kimble RB, Valenzuela DM, Yancopoulos GD, Wilkie AO

Title

Dominant mutations in ROR2, encoding an orphan receptor tyrosine kinase, cause brachydactyly type B.

Journal

Nat Genet 24:275-8 (2000)
DOI:10.1038/73495

Reference

PMID:17668388 (NOG)

Authors

Lehmann K, Seemann P, Silan F, Goecke TO, Irgang S, Kjaer KW, Kjaergaard S, Mahoney MJ, Morlot S, Reissner C, Kerr B, Wilkie AO, Mundlos S

Title

A new subtype of brachydactyly type B caused by point mutations in the bone morphogenetic protein antagonist NOGGIN.

Journal

Am J Hum Genet 81:388-96 (2007)
DOI:10.1086/519697

Reference

PMID:12649808 (HOXD13)

Authors

Johnson D, Kan SH, Oldridge M, Trembath RC, Roche P, Esnouf RM, Giele H, Wilkie AO

Title

Missense mutations in the homeodomain of HOXD13 are associated with brachydactyly types D and E.

Journal

Am J Hum Genet 72:984-97 (2003)
DOI:10.1086/374721

Reference

PMID:20170896 (PTHLH)

Authors

Klopocki E, Hennig BP, Dathe K, Koll R, de Ravel T, Baten E, Blom E, Gillerot Y, Weigel JF, Kruger G, Hiort O, Seemann P, Mundlos S

Title

Deletion and point mutations of PTHLH cause brachydactyly type E.

Journal

Am J Hum Genet 86:434-9 (2010)
DOI:10.1016/j.ajhg.2010.01.023

Reference

PMID:25961942 (PDE3A)

Authors

Maass PG, Aydin A, Luft FC, Schachterle C, Weise A, Stricker S, Lindschau C, Vaegler M, Qadri F, Toka HR, Schulz H, Krawitz PM, Parkhomchuk D, Hecht J, Hollfinger I, Wefeld-Neuenfeld Y, Bartels-Klein E, Muhl A, Kann M, Schuster H, Chitayat D, Bialer MG, Wienker TF, Ott J, Rittscher K, Liehr T, Jordan J, Plessis G, Tank J, Mai K, Naraghi R, Hodge R, Hopp M, Hattenbach LO, Busjahn A, Rauch A, Vandeput F, Gong M, Ruschendorf F, Hubner N, Haller H, Mundlos S, Bilginturan N, Movsesian MA, Klussmann E, Toka O, Bahring S

Title

PDE3A mutations cause autosomal dominant hypertension with brachydactyly.

Journal

Nat Genet 47:647-53 (2015)
DOI:10.1038/ng.3302

LinkDB

» Japanese version

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