KEGG DISEASE: Brachydactyly

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

DISEASE: Acromesomelic dysplasia

Entry

H02543                      Disease

Name

Acromesomelic dysplasia

Subgroup

Acromesomelic dysplasia, Maroteaux type (AMD1) [DS:H00470]
Grebe dysplasia (AMD2) [DS:H00466]
Acromesomelic dysplasia 2B (AMD2B) [DS:H00467]
Acromesomelic dysplasia, Demirhan type (AMD3) [DS:H00468]

Description

Acromesomelic dysplasia (AMD) is a group of autosomal recessive form of skeletal disorders characterized by dwarfism associated with anomalies of middle and distal segments of the extremities. Mutations in four genes (GDF5, NPR2, BMPR1B, and PRKG2) have been reported to cause different forms of AMD.

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
    H02543  Acromesomelic dysplasia
Pathway-based classification of diseases [BR:br08402]
Signal transduction
  nt06507  TGFB signaling
   H02543  Acromesomelic dysplasia
Endocrine system
  nt06325  Hormone/cytokine signaling
   H02543  Acromesomelic dysplasia

Pathway

hsa04022

cGMP-PKG signaling pathway

hsa04350

TGF-beta signaling pathway

hsa04390

Hippo signaling pathway

Network

nt06325 Hormone/cytokine signaling
nt06507 TGFB signaling

Gene

(AMD1) NPR2 [HSA:4882] [KO:K12324]
(AMD2) GDF5 [HSA:8200] [KO:K04664]
(AMD3) BMPR1B [HSA:658] [KO:K13578]
(AMD4) PRKG2 [HSA:5593] [KO:K19477]

Other DBs

ICD-11:

LD24.9

OMIM:

619636

Reference

PMID:26926249 (AMD1-3)

Authors

Khan S, Basit S, Khan MA, Muhammad N, Ahmad W

Title

Genetics of human isolated acromesomelic dysplasia.

Journal

Eur J Med Genet 59:198-203 (2016)
DOI:10.1016/j.ejmg.2016.02.011

Reference

PMID:33106379 (AMD4)

Authors

Diaz-Gonzalez F, Wadhwa S, Rodriguez-Zabala M, Kumar S, Aza-Carmona M, Sentchordi-Montane L, Alonso M, Ahmad I, Zahra S, Kumar D, Kushwah N, Shamim U, Sait H, Kapoor S, Roldan B, Nishimura G, Offiah AC, Faruq M, Heath KE

Title

Biallelic cGMP-dependent type II protein kinase gene (PRKG2) variants cause a novel acromesomelic dysplasia.

Journal

J Med Genet jmedgenet-2020-107177 (2020)
DOI:10.1136/jmedgenet-2020-107177

LinkDB

» Japanese version

DISEASE: Multiple synostosis syndrome

Entry

H00484                      Disease

Name

Multiple synostosis syndrome

Description

Proximal symphalangism is a condition characterized by variable fusion of the proximal interphalangeal joints. Multiple synostosis syndrome (SYNS) is a more severe form of proximal symphalangism with additional bone fusions involving carpal, tarsal, and other joints.

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
    LB90  Joint formation defects
     H00484  Multiple synostosis syndrome
Pathway-based classification of diseases [BR:br08402]
Signal transduction
  nt06507  TGFB signaling
   H00484  Multiple synostosis syndrome

Pathway

hsa04350

TGF-beta signaling pathway

Network

nt06507 TGFB signaling

Gene

(SYNS1) NOG [HSA:9241] [KO:K04658]
(SYNS2) GDF5 [HSA:8200] [KO:K04664]
(SYNS3) FGF9 [HSA:2254] [KO:K04358]
(SYNS4) GDF6 [HSA:392255] [KO:K20012]

Other DBs

ICD-11:

LB90.Y

MeSH:

C536943 C537380 C567839

OMIM:

186500 610017 612961 617898

Reference

PMID:7428777

Authors

Pedersen JC, Fryns JP, Carpentier G, Heremans G, Van den Berghe H

Title

Multiple synostosis syndrome.

Journal

Eur J Pediatr 134:273-5 (1980)
DOI:10.1007/BF00441486

Reference

PMID:10080184 (SYNS1)

Authors

Gong Y, Krakow D, Marcelino J, Wilkin D, Chitayat D, Babul-Hirji R, Hudgins L, Cremers CW, Cremers FP, Brunner HG, Reinker K, Rimoin DL, Cohn DH, Goodman FR, Reardon W, Patton M, Francomano CA, Warman ML

Title

Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis.

Journal

Nat Genet 21:302-4 (1999)
DOI:10.1038/6821

Reference

PMID:16532400 (SYNS2)

Authors

Dawson K, Seeman P, Sebald E, King L, Edwards M, Williams J 3rd, Mundlos S, Krakow D

Title

GDF5 is a second locus for multiple-synostosis syndrome.

Journal

Am J Hum Genet 78:708-12 (2006)
DOI:10.1086/503204

Reference

PMID:19589401 (SYNS3)

Authors

Wu XL, Gu MM, Huang L, Liu XS, Zhang HX, Ding XY, Xu JQ, Cui B, Wang L, Lu SY, Chen XY, Zhang HG, Huang W, Yuan WT, Yang JM, Gu Q, Fei J, Chen Z, Yuan ZM, Wang ZG

Title

Multiple synostoses syndrome is due to a missense mutation in exon 2 of FGF9 gene.

Journal

Am J Hum Genet 85:53-63 (2009)
DOI:10.1016/j.ajhg.2009.06.007

Reference

PMID:26643732 (SYNS4)

Authors

Wang J, Yu T, Wang Z, Ohte S, Yao RE, Zheng Z, Geng J, Cai H, Ge Y, Li Y, Xu Y, Zhang Q, Gusella JF, Fu Q, Pregizer S, Rosen V, Shen Y

Title

A New Subtype of Multiple Synostoses Syndrome Is Caused by a Mutation in GDF6 That Decreases Its Sensitivity to Noggin and Enhances Its Potency as a BMP Signal.

Journal

J Bone Miner Res 31:882-9 (2016)
DOI:10.1002/jbmr.2761

LinkDB

» Japanese version

DISEASE: Proximal symphalangism

Entry

H00851                      Disease

Name

Proximal symphalangism

Description

Proximal symphalangism (SYM) is an autosomal-dominant condition characterized by variable fusion of the proximal interphalangeal joints.

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
    LB90  Joint formation defects
     H00851  Proximal symphalangism
Pathway-based classification of diseases [BR:br08402]
Signal transduction
  nt06507  TGFB signaling
   H00851  Proximal symphalangism

Network

nt06507 TGFB signaling

Gene

(SYM1A) NOG [HSA:9241] [KO:K04658]
(SYM1B) GDF5 [HSA:8200] [KO:K04664]

Other DBs

ICD-11:

LB90.Y

MeSH:

C536223

OMIM:

185800 615298

Reference