Loeys-Dietz syndrome is an autosomal dominant connective tissue disorder which has many features similar to Marfan syndrome.
The disease is characterized by skeletal manifestations and vasculopathies. Although Loeys-Dietz syndrome shares many similarities with Marfan syndrome, the course is often more aggressive with respect to vasculopathy and is more likely to affect peripheral arteries.
The classical triad of Loeys-Dietz syndrome is described as 1:
Loeys-Dietz syndrome is rare, with prevalence estimated at less than one per 100,000.
Disease spectrum and associated features include:
- cleft palate
- bifid uvula
- malar hypoplasia
- blue sclerae
- Chiari I malformation
- aortic dissection
- aortic dilatation
- non-aortic aneurysms (a distinguishing feature of Loeys-Dietz syndrome), including:
- arterial tortuosity
- associated congenital cardiac abnormalities:
- mitral valve prolapse
- left ventricular hypertrophy
- pectus carinatum
- talipes equinovarus
- joint laxity
- dolichostenomelia (unusually long limbs)
- cervical spine instability
- developmental delay
- environmental allergies
- dural ectasia
It is caused by mutations in the genes encoding transforming growth factor-beta receptor 1 (TGFBR1) or 2 (TGFBR2). Although Loeys-Dietz syndrome is inherited in an autosomal dominant pattern, de novo mutations account for approximately 75% of cases.
Loeys-Dietz syndrome can be subdivided into four subtypes depending on their genetic mutations and resulting phenotypic features.
type I: predominantly craniofacial features
- TGFBR1 mutation; chromosome 9q22
type II: predominantly cutaneous features
- TGFBR2 mutation; chromosome 3p22
type III: predominantly aneurysm-osteoarthritis features
- SMAD3 mutation; chromosome 15q
type IV: predominantly Marfanoid features
- TGFB2 mutation; chromosome 1q41
Please refer to individual articles for the respective characteristics.
History and etymology
It is named after Harry C Dietz, an American physician, and Bart L Loeys 1, a Belgian physician.
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