Loeys-Dietz syndrome

Loeys-Dietz syndrome (LDS) is an autosomal dominant genetic syndromeconnective tissue disorder which has many features similar to Marfan syndrome.

The disease is characterised by skeletal manifestations and vasculopathies. Although LDS shares many similarities with Marfan syndrome features a, the course is often more aggressive with respect to vasculopathy and is more likely to affect peripheral arteries.

The classical triad of LDS is described as¹:

• arterial tortuosity and aneurysms
• hypertelorism
• bifid uvula or cleft palate

Pathology

It is caused by mutations in the genes encoding transforming growth factor beta receptor 1 (TGFBR1) or 2 (TGFBR2). Although LDS is inherited in an autosomal dominant pattern, de novo mutations account for approximately 75% of cases.

Subtypes

LDS can be subdivided in LDS into four subtypes depending on their genetic mutations and resulting phenotypic features.

• type I (LDSI): 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

Disease spectrum and type II (LDSIIassociated features

Craniofacial

• hypertelorism
• cleft palate
• bifid uvula
• craniosynostosis
• malar hypoplasia
• blue sclerae
• Chiari I malformation
• hydrocephalus

Cardiovascular

• aortic dissection
• aortic dilatation
• non-aortic aneurysms (a distinguishing feature of LDS) on, including:
  • popliteal artery aneurysm
  • internal thoracic artery aneurysm
  • common iliac aneurysm
  • splenic artery aneurysm
  • intracranial aneurysm
• arterial tortuosity 
• associated congenital cardiac abnormalities:
  • patent ductus arteriosus
  • atrial septal defects
• mitral valve prolapse
• left ventricular hypertrophy

Musculoskeletal

• arachnodactyly 
• camptodactyly
• pectus carinatum
• scoliosis
• talipes equinovarus
• joint laxity
• dolichosternomelia
• cervical spine instability 

Other

• developmental delay
• environmental allergies
• dural ectasia

Radiographic evaluation

Please refer to individual articles for the basis of the presence or the absence of craniofacial involvementrespective characteristics.

History and etymology

It is named after Harry C. Dietz, an American (US) physician and Bart L. Loeys ¹ a Belgian physician.