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Loeys-Dietz syndrome 6(LDS6)

MedGen UID:
1794251
Concept ID:
C5562041
Disease or Syndrome
Synonyms: LDS6; LOEYS-DIETZ SYNDROME 6
 
Gene (location): SMAD2 (18q21.1)
 
Monarch Initiative: MONDO:0030500
OMIM®: 619656

Disease characteristics

Excerpted from the GeneReview: Loeys-Dietz Syndrome
Loeys-Dietz syndrome (LDS) is characterized by vascular findings (cerebral, thoracic, and abdominal arterial aneurysms and/or dissections), skeletal manifestations (pectus excavatum or pectus carinatum, scoliosis, joint laxity, arachnodactyly, talipes equinovarus, cervical spine malformation and/or instability), craniofacial features (widely spaced eyes, strabismus, bifid uvula / cleft palate, and craniosynostosis that can involve any sutures), and cutaneous findings (velvety and translucent skin, easy bruising, and dystrophic scars). Individuals with LDS are predisposed to widespread and aggressive arterial aneurysms and pregnancy-related complications including uterine rupture and death. Individuals with LDS can show a strong predisposition for allergic/inflammatory disease including asthma, eczema, and reactions to food or environmental allergens. There is also an increased incidence of gastrointestinal inflammation including eosinophilic esophagitis and gastritis or inflammatory bowel disease. Wide variation in the distribution and severity of clinical features can be seen in individuals with LDS, even among affected individuals within a family who have the same pathogenic variant. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  Chapter Notes  |  References
Authors:
Bart L Loeys  |  Harry C Dietz   view full author information

Additional description

From OMIM
Loeys-Dietz syndrome-6 (LDS6) is characterized by aortic/arterial aneurysm and dissection in association with connective tissue findings. Most patients have thoracic aortic aneurysm involving the ascending aorta and/or aortic root, but cerebral and iliac arteries can be affected, and abdominal aortic aneurysm has been observed. Arterial tortuosity involving cerebral vessels, the aorta, and/or iliac arteries has also been reported (Granadillo et al., 2018; Cannaerts et al., 2019). For a general phenotypic description and discussion of genetic heterogeneity of LDS, see LDS1 (609192).  http://www.omim.org/entry/619656

Clinical features

From HPO
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Chronic fatigue
MedGen UID:
760077
Concept ID:
C0518656
Finding
Subjective feeling of tiredness characterized by a lack of energy and motivation that persists for six months or longer.
Arachnodactyly
MedGen UID:
2047
Concept ID:
C0003706
Congenital Abnormality
Abnormally long and slender fingers ("spider fingers").
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.
Osteoarthritis, knee
MedGen UID:
98371
Concept ID:
C0409959
Disease or Syndrome
Noninflammatory degenerative disease of the knee joint consisting of three large categories: conditions that block normal synchronous movement, conditions that produce abnormal pathways of motion, and conditions that cause stress concentration resulting in changes to articular cartilage. (Crenshaw, Campbell's Operative Orthopaedics, 8th ed, p2019)
Varicose disease
MedGen UID:
21827
Concept ID:
C0042345
Disease or Syndrome
Enlarged and tortuous veins.
Abdominal aortic aneurysm
MedGen UID:
56524
Concept ID:
C0162871
Anatomical Abnormality
An abnormal localized widening (dilatation) of the abdominal aorta.
Thoracic aortic aneurysm
MedGen UID:
56525
Concept ID:
C0162872
Anatomical Abnormality
An abnormal localized widening (dilatation) of the thoracic aorta.
Carotid artery dissection
MedGen UID:
488844
Concept ID:
C0338585
Disease or Syndrome
A separation (dissection) of the layers of the carotid artery wall.
Ventricular hypertrophy
MedGen UID:
87400
Concept ID:
C0340279
Disease or Syndrome
Enlargement of the cardiac ventricular muscle tissue with increase in the width of the wall of the ventricle and loss of elasticity. Ventricular hypertrophy is clinically differentiated into left and right ventricular hypertrophy.
Vertebral artery aneurysm
MedGen UID:
657756
Concept ID:
C0574027
Anatomical Abnormality
Abnormal outpouching or sac-like dilatation in the wall of the vertebral artery .
Dilatation of the cerebral artery
MedGen UID:
1386760
Concept ID:
C4476540
Anatomical Abnormality
The presence of a localized dilatation or ballooning of a cerebral artery.
Carotid artery dilatation
MedGen UID:
1393749
Concept ID:
C4476554
Anatomical Abnormality
A dilatation (balooning or bulging out of the vessel wall) of a carotid artery.
Disproportionate tall stature
MedGen UID:
323048
Concept ID:
C1836996
Finding
A tall and slim body build with increased arm span to height ratio (>1.05) and a reduced upper-to-lower segment ratio (<0.85), i.e., unusually long arms and legs. The extremities as well as the hands and feet are unusually slim.
Osteoarthritis of hip
MedGen UID:
14530
Concept ID:
C0029410
Disease or Syndrome
Osteoarthritis of the hip joint.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Intervertebral disc degeneration
MedGen UID:
102357
Concept ID:
C0158266
Disease or Syndrome
The presence of degenerative changes of intervertebral disk.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Long face
MedGen UID:
324419
Concept ID:
C1836047
Finding
Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective).
Striae distensae
MedGen UID:
57541
Concept ID:
C0152459
Acquired Abnormality
Thinned, erythematous, depressed bands of atrophic skin. Initially, striae appear as flattened and thinned, pinkish linear regions of the skin. Striae tend to enlarge in length and become reddish or purplish. Later, striae tend to appear as white, depressed bands that are parallel to the lines of skin tension. Striae distensae occur most often in areas that have been subject to distension such as the lower back, buttocks, thighs, breast, abdomen, and shoulders.

Professional guidelines

PubMed

Schoenhoff FS, Alejo DE, Black JH, Crawford TC, Dietz HC, Grimm JC, Magruder JT, Patel ND, Vricella LA, Young A, Carrel TP, Cameron DE
J Thorac Cardiovasc Surg 2020 Nov;160(5):1166-1175. Epub 2019 Sep 9 doi: 10.1016/j.jtcvs.2019.07.130. PMID: 31627951
Colombi M, Dordoni C, Chiarelli N, Ritelli M
Am J Med Genet C Semin Med Genet 2015 Mar;169C(1):6-22. doi: 10.1002/ajmg.c.31429. PMID: 25821090
Paterick TE, Humphries JA, Ammar KA, Jan MF, Loberg R, Bush M, Khandheria BK, Tajik AJ
Am J Med 2013 Aug;126(8):670-8. Epub 2013 Jun 22 doi: 10.1016/j.amjmed.2013.01.029. PMID: 23800581

Curated

UK NICE Guideline NG156, Abdominal aortic aneurysm: diagnosis and management, 2020

Recent clinical studies

Etiology

Wang Y, Starovoytov A, Murad AM, Hunker KL, Brunham LR, Li JZ, Saw J, Ganesh SK
JAMA Cardiol 2022 Oct 1;7(10):1045-1055. doi: 10.1001/jamacardio.2022.2970. PMID: 36103205Free PMC Article
Braverman AC, Mittauer E, Harris KM, Evangelista A, Pyeritz RE, Brinster D, Conklin L, Suzuki T, Fanola C, Ouzounian M, Chen E, Myrmel T, Bekeredjian R, Hutchison S, Coselli J, Gilon D, O'Gara P, Davis M, Isselbacher E, Eagle K
JAMA Cardiol 2021 Jan 1;6(1):58-66. doi: 10.1001/jamacardio.2020.4876. PMID: 33052376Free PMC Article
Marrache M, Byers PH, Sponseller PD
JBJS Rev 2020 Jun;8(6):e0122. doi: 10.2106/JBJS.RVW.19.00122. PMID: 33006458
Skeik N, Hyde JR, Olson SL, Thaler CM, Abuatiyeh W, Ahmed AK, Lyon DR, Witt DR, Garberich R, Sullivan T
Ann Vasc Surg 2019 Oct;60:128-146. Epub 2019 Jun 12 doi: 10.1016/j.avsg.2019.04.004. PMID: 31200053
Busch C, Voitl R, Goergen B, Zemojtel T, Gehle P, Salchow DJ
Br J Ophthalmol 2018 Aug;102(8):1036-1040. Epub 2017 Nov 16 doi: 10.1136/bjophthalmol-2017-311254. PMID: 29146755

Diagnosis

Braverman AC, Mittauer E, Harris KM, Evangelista A, Pyeritz RE, Brinster D, Conklin L, Suzuki T, Fanola C, Ouzounian M, Chen E, Myrmel T, Bekeredjian R, Hutchison S, Coselli J, Gilon D, O'Gara P, Davis M, Isselbacher E, Eagle K
JAMA Cardiol 2021 Jan 1;6(1):58-66. doi: 10.1001/jamacardio.2020.4876. PMID: 33052376Free PMC Article
Camerota L, Ritelli M, Wischmeijer A, Majore S, Cinquina V, Fortugno P, Monetta R, Gigante L, Marfan Syndrome Study Group Tor Vergata University Hospital, Sangiuolo FC, Novelli G, Colombi M, Brancati F
Genes (Basel) 2019 Sep 28;10(10) doi: 10.3390/genes10100764. PMID: 31569402Free PMC Article
Skeik N, Hyde JR, Olson SL, Thaler CM, Abuatiyeh W, Ahmed AK, Lyon DR, Witt DR, Garberich R, Sullivan T
Ann Vasc Surg 2019 Oct;60:128-146. Epub 2019 Jun 12 doi: 10.1016/j.avsg.2019.04.004. PMID: 31200053
Boone PM, Scott RM, Marciniak SJ, Henske EP, Raby BA
Am J Respir Crit Care Med 2019 Jun 1;199(11):1344-1357. doi: 10.1164/rccm.201807-1212CI. PMID: 30681372Free PMC Article
Colombi M, Dordoni C, Chiarelli N, Ritelli M
Am J Med Genet C Semin Med Genet 2015 Mar;169C(1):6-22. doi: 10.1002/ajmg.c.31429. PMID: 25821090

Therapy

van Dorst DCH, de Wagenaar NP, van der Pluijm I, Roos-Hesselink JW, Essers J, Danser AHJ
Cardiovasc Drugs Ther 2021 Dec;35(6):1233-1252. Epub 2020 Dec 7 doi: 10.1007/s10557-020-07116-4. PMID: 33283255Free PMC Article
Chivulescu M, Krohg-Sørensen K, Scheirlynck E, Lindberg BR, Dejgaard LA, Lie ØH, Helle-Valle T, Skjølsvik ET, Estensen ME, Edvardsen T, Lingaas PS, Haugaa KH
Eur Heart J Cardiovasc Imaging 2021 Aug 14;22(9):1035-1044. doi: 10.1093/ehjci/jeaa324. PMID: 33280029Free PMC Article
Skeik N, Hyde JR, Olson SL, Thaler CM, Abuatiyeh W, Ahmed AK, Lyon DR, Witt DR, Garberich R, Sullivan T
Ann Vasc Surg 2019 Oct;60:128-146. Epub 2019 Jun 12 doi: 10.1016/j.avsg.2019.04.004. PMID: 31200053
Beaulieu RJ, Lue J, Ehlert BA, Grimm JC, Hicks CW, Black JH 3rd
Ann Vasc Surg 2017 Jan;38:10-16. Epub 2016 Aug 10 doi: 10.1016/j.avsg.2016.06.007. PMID: 27521820
Verstraeten A, Alaerts M, Van Laer L, Loeys B
Hum Mutat 2016 Jun;37(6):524-31. Epub 2016 Mar 14 doi: 10.1002/humu.22977. PMID: 26919284

Prognosis

Braverman AC, Mittauer E, Harris KM, Evangelista A, Pyeritz RE, Brinster D, Conklin L, Suzuki T, Fanola C, Ouzounian M, Chen E, Myrmel T, Bekeredjian R, Hutchison S, Coselli J, Gilon D, O'Gara P, Davis M, Isselbacher E, Eagle K
JAMA Cardiol 2021 Jan 1;6(1):58-66. doi: 10.1001/jamacardio.2020.4876. PMID: 33052376Free PMC Article
Skeik N, Hyde JR, Olson SL, Thaler CM, Abuatiyeh W, Ahmed AK, Lyon DR, Witt DR, Garberich R, Sullivan T
Ann Vasc Surg 2019 Oct;60:128-146. Epub 2019 Jun 12 doi: 10.1016/j.avsg.2019.04.004. PMID: 31200053
Aftab M, Cikach FS, Zhu Y, Idrees JJ, Rigelsky CM, Kalahasti V, Roselli EE, Svensson LG
J Thorac Cardiovasc Surg 2019 Feb;157(2):439-450.e5. Epub 2018 Apr 30 doi: 10.1016/j.jtcvs.2018.03.172. PMID: 30669217
Van Hemelrijk C, Renard M, Loeys B
Curr Opin Cardiol 2010 Nov;25(6):546-51. doi: 10.1097/HCO.0b013e32833f0220. PMID: 20838339
Loeys BL, Schwarze U, Holm T, Callewaert BL, Thomas GH, Pannu H, De Backer JF, Oswald GL, Symoens S, Manouvrier S, Roberts AE, Faravelli F, Greco MA, Pyeritz RE, Milewicz DM, Coucke PJ, Cameron DE, Braverman AC, Byers PH, De Paepe AM, Dietz HC
N Engl J Med 2006 Aug 24;355(8):788-98. doi: 10.1056/NEJMoa055695. PMID: 16928994

Clinical prediction guides

Wang Y, Starovoytov A, Murad AM, Hunker KL, Brunham LR, Li JZ, Saw J, Ganesh SK
JAMA Cardiol 2022 Oct 1;7(10):1045-1055. doi: 10.1001/jamacardio.2022.2970. PMID: 36103205Free PMC Article
Kim ST, Brinjikji W, Lanzino G, Kallmes DF
Interv Neuroradiol 2016 Dec;22(6):624-637. Epub 2016 Aug 10 doi: 10.1177/1591019916659262. PMID: 27511817Free PMC Article
Blinc A, Maver A, Rudolf G, Tasič J, Pretnar Oblak J, Berden P, Peterlin B
Eur J Vasc Endovasc Surg 2015 Dec;50(6):816-21. Epub 2015 Sep 26 doi: 10.1016/j.ejvs.2015.08.003. PMID: 26409702
Morris SA
Curr Opin Cardiol 2015 Nov;30(6):587-93. doi: 10.1097/HCO.0000000000000218. PMID: 26398550Free PMC Article
Loeys BL, Schwarze U, Holm T, Callewaert BL, Thomas GH, Pannu H, De Backer JF, Oswald GL, Symoens S, Manouvrier S, Roberts AE, Faravelli F, Greco MA, Pyeritz RE, Milewicz DM, Coucke PJ, Cameron DE, Braverman AC, Byers PH, De Paepe AM, Dietz HC
N Engl J Med 2006 Aug 24;355(8):788-98. doi: 10.1056/NEJMoa055695. PMID: 16928994

Recent systematic reviews

Charoenngam N, Rittiphairoj T, Ponvilawan B, Jaroenlapnopparat A, Waitayangkoon P, Suppakitjanusant P, Prasitsumrit V, Pongchaiyakul C, Holick MF
Endocr Pract 2023 Jul;29(7):589-600. Epub 2023 Feb 17 doi: 10.1016/j.eprac.2023.02.003. PMID: 36804968
Velvin G, Wilhelmsen JE, Johansen H, Bathen T, Geirdal AØ
Clin Genet 2019 Jun;95(6):661-676. Epub 2019 Apr 2 doi: 10.1111/cge.13522. PMID: 30788842

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.

    Curated

    • NICE, 2020
      UK NICE Guideline NG156, Abdominal aortic aneurysm: diagnosis and management, 2020

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