Loeys-dietz syndromeQ87.40
Synonym(s)
HistoryThis section has been translated automatically.
Loeys, 2005
DefinitionThis section has been translated automatically.
Rare multi-organ disease that clinically overlaps with Marfan syndrome (MFS) in some organ manifestations. However, the lens shift, which is one of the diagnostic criteria in MFS, is always absent. On the other hand, LDS presents with symptoms that are uncommon in MFS.
People with Loeys-Dietz syndrome often develop immunological disorders: food allergies, asthma or signs of atopic dermatitis or inflammatory bowel disease.
ClassificationThis section has been translated automatically.
To date, five different genotypes are known in Loeys-Dietz syndrome, referred to as types I through V.
EtiopathogenesisThis section has been translated automatically.
The five types of Loeys-Dietz syndrome are distinguished according to their genetic cause:
- TGFBR1 gene mutations cause type I
- TGFBR2 gene mutations cause type II
- SMAD3 gene mutations cause type III
- TGFB2 gene mutations cause type IV
- TGFB3 gene mutations cause type V.
These five genes play a role in the TGF-β signaling pathway, which controls the functions of body cells during growth and development. This signaling pathway also regulates the formation of the extracellular matrix. The defective proteins encoded by these genes lead to a pathological increase in the activity of the TGF-β signaling pathway. This disrupts the development of the extracellular matrix and various body systems.
ManifestationThis section has been translated automatically.
The signs and symptoms of Loeys-Dietz syndrome can occur from childhood into adulthood. The severity varies.
Clinical featuresThis section has been translated automatically.
Hypertelorism and a split uvula or cleft palate are particularly noticeable.
The following symptoms can also occur, but are not necessarily present in every patient:
- Aneurysm of the aortic root and other vascular areas
- Dissections of the aorta and other major vascular systems
- Tortuosity of the arteries
- Retinal detachments
- Blue shimmering leather skin (sclera)
- Striae cutis distensae
- Translucent veins
- Tendency to hematomas
- Soft, delicate skin with atrophic scars
- Curvature of the spine
- Deformation of the sternum inwards or outwards
- Clubfoot
- Narrow, high palate
- Hypermobility of the joints
- Slender hands with long fingers (spider fingers)
- Skull malformations due to premature ossification (craniosynostosis)
TherapyThis section has been translated automatically.
Causal therapy not possible. Organ-related clinical controls and therapies.
Progression/forecastThis section has been translated automatically.
As in Marfan syndrome, the prognosis of the disease depends on the cardiological involvement.
LiteratureThis section has been translated automatically.
- Arslan-Kirchner M et al. (2911) Clinical utility gene card for: Loeys-Dietz syndrome (TGFBR1/2) and related phenotypes. Eur J Hum Genet 19. doi: 10.1038/ejhg.2011.68.
- Bertoli-Avella AM et al (2015) Mutations in a TGF-β ligand, TGFB3, cause syndromic aortic aneurysms and dissections. J Am Coll Cardiol 65:1324-1336.
- Boodhwani M et al.(2014) Canadian Cardiovascular Society position statement on the management of thoracic aortic disease. Can J Cardiol 30:577-589.
- Erbel R et al. (2014) ESC Guidelines on the diagnosis and treatment of aortic diseases: Document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC). Eur Heart J 35:2873-2926.
- Felgentreff K et al (2014) Severe eczema and hyper-IgE in Loeys-Dietz-syndrome - contribution to new findings of immune dysregulation in connective tissue disorders. Clin Immunol 150: 43-50.
- Frischmeyer-Guerrerio PA et al (2013) TGFβ receptor mutations impose a strong predisposition for human allergic disease. Sci Transl Med 5:195ra94.
- Loeys BL (2012) Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm. Nat Genet 44:922-927.
- Loeys BL et al (2005) A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletaldevelopment caused by mutations in TGFBR1 or TGFBR2. Nat Genet 37:275-81.
- MacCarrick G et al (2014) Loeys-Dietz syndrome: a primer for diagnosis and management. Genet Med 16:576-587.
- Verhagen JMA et al (2018) National Working Group on BAV & TAA. Expert consensus recommendations on the cardiogenetic care for patients with thoracic aortic disease and their first-degree relatives. Int J Cardiol 258:243-248.