KEGG DISEASE: Loeys-Dietz syndrome

DISEASE: Loeys-Dietz syndrome

Entry

H00800                      Disease

Name

Loeys-Dietz syndrome

Subgroup

Rienhoff syndrome [DS:H01385]

Description

Loeys-Dietz syndrome (LDS) is an autosomal dominant disorder characterized by arterial aneurysms and dissections, pectus excavatum, craniosynostosis, cleft palate, congenital heart disease, and thin, translucent skin. LDS results from mutations in the TGF beta receptor genes. LDS has been subdivided in LDS1 and LDS2 on the basis of the presence or the absence of craniofacial involvement, respectively. LDS3 is associated with early-onset osteoarthritis and caused by mutation in the SMAD3 gene. LDS4 and LDS5 are caused by mutation in the TGFB2 and TGFB3 gene, respectively.

Category

Congenital malformation

Brite

Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
  Multiple developmental anomalies or syndromes
   LD28  Syndromes with connective tissue involvement as a major feature
    H00800  Loeys-Dietz syndrome
Pathway-based classification of diseases [BR:br08402]
Signal transduction
  nt06507  TGFB signaling
   H00800  Loeys-Dietz syndrome

Pathway

hsa04350

TGF-beta signaling pathway

Network

nt06507 TGFB signaling

Gene

(LDS1A/2A) TGFBR1 [HSA:7046] [KO:K04674]
(LDS1B/2B) TGFBR2 [HSA:7048] [KO:K04388]
(LDS3) SMAD3 [HSA:4088] [KO:K23605]
(LDS4) TGFB2 [HSA:7042] [KO:K13376]
(LDS5) TGFB3 [HSA:7043] [KO:K13377]
(LDS6) SMAD2 [HSA:4087] [KO:K04500]

Comment

LDS and Marfan syndrome [DS:H00653] are both genetic disorders of connective tissue and share many features.

Other DBs

ICD-11:

LD28.01

ICD-10:

I71.0

MeSH:

D055947

OMIM:

609192 608967 610168 610380 613795 614816 615582 619656

Reference

PMID:21785848

Authors

Kalra VB, Gilbert JW, Malhotra A

Title

Loeys-Dietz syndrome: cardiovascular, neuroradiological and musculoskeletal imaging findings.

Journal

Pediatr Radiol 41:1495-504 (2011)
DOI:10.1007/s00247-011-2195-z

Reference

PMID:18544034

Authors

Milewicz DM, Guo DC, Tran-Fadulu V, Lafont AL, Papke CL, Inamoto S, Kwartler CS, Pannu H

Title

Genetic basis of thoracic aortic aneurysms and dissections: focus on smooth muscle cell contractile dysfunction.

Journal

Annu Rev Genomics Hum Genet 9:283-302 (2008)
DOI:10.1146/annurev.genom.8.080706.092303

Reference

PMID:19883511 (LDS1_2)

Authors

Drera B, Ritelli M, Zoppi N, Wischmeijer A, Gnoli M, Fattori R, Calzavara-Pinton PG, Barlati S, Colombi M

Title

Loeys-Dietz syndrome type I and type II: clinical findings and novel mutations in two Italian patients.

Journal

Orphanet J Rare Dis 4:24 (2009)
DOI:10.1186/1750-1172-4-24

Reference

PMID:21217753 (LDS3)

Authors

van de Laar IM, Oldenburg RA, Pals G, Roos-Hesselink JW, de Graaf BM, Verhagen JM, Hoedemaekers YM, Willemsen R, Severijnen LA, Venselaar H, Vriend G, Pattynama PM, Collee M, Majoor-Krakauer D, Poldermans D, Frohn-Mulder IM, Micha D, Timmermans J, Hilhorst-Hofstee Y, Bierma-Zeinstra SM, Willems PJ, Kros JM, Oei EH, Oostra BA, Wessels MW, Bertoli-Avella AM

Title

Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis.

Journal

Nat Genet 43:121-6 (2011)
DOI:10.1038/ng.744

Reference

PMID:22772368 (LDS4)

Authors

Lindsay ME, Schepers D, Bolar NA, Doyle JJ, Gallo E, Fert-Bober J, Kempers MJ, Fishman EK, Chen Y, Myers L, Bjeda D, Oswald G, Elias AF, Levy HP, Anderlid BM, Yang MH, Bongers EM, Timmermans J, Braverman AC, Canham N, Mortier GR, Brunner HG, Byers PH, Van Eyk J, Van Laer L, Dietz HC, Loeys BL

Title

Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm.

Journal

Nat Genet 44:922-7 (2012)
DOI:10.1038/ng.2349

Reference

PMID:23824657 (LDS5)

Authors

Rienhoff HY Jr, Yeo CY, Morissette R, Khrebtukova I, Melnick J, Luo S, Leng N, Kim YJ, Schroth G, Westwick J, Vogel H, McDonnell N, Hall JG, Whitman M

Title

A mutation in TGFB3 associated with a syndrome of low muscle mass, growth retardation, distal arthrogryposis and clinical features overlapping with Marfan and Loeys-Dietz syndrome.

Journal

Am J Med Genet A 161A:2040-6 (2013)
DOI:10.1002/ajmg.a.36056

Reference

PMID:29967133 (LDS6)

Authors

Cannaerts E, Kempers M, Maugeri A, Marcelis C, Gardeitchik T, Richer J, Micha D, Beauchesne L, Timmermans J, Vermeersch P, Meyten N, Chenier S, van de Beek G, Peeters N, Alaerts M, Schepers D, Van Laer L, Verstraeten A, Loeys B

Title

Novel pathogenic SMAD2 variants in five families with arterial aneurysm and dissection: further delineation of the phenotype.

Journal

J Med Genet 56:220-227 (2019)
DOI:10.1136/jmedgenet-2018-105304

» Japanese version

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Network (7)   
   KEGG NETWORK (1)   
   KEGG VARIANT (6)   
Disease (8)   
   OMIM (8)   
Gene (12)   
   KEGG ORTHOLOGY (6)   
   KEGG GENES (6)   
Literature (7)   
   PubMed (7)   
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