Loeys-Dietz syndrome, type 1B (LDS1B)

Loeys-Dietz syndrome

Loeys-Dietz syndrome, type 1A (LDS1A; MIM 609192) and type 1B (LDS1B; MIM 610168) are caused by mutations in the TGFBR1 and TGFBR2 genes respectively. The reported phenotype is highly variable and overlaps considerably with Ehlers-Danlos syndrome IV (EDS IV; MIM 130050) or Marfan syndrome (MFS; MIM 154700). A high percentage of patients have aortic root aneurysm or other arterial aneurysms. Some have cardiac abnormalities including patent ductus or atrial septal defects. Many display arterial tortuosity. Skeletal defects may include hypertelorism, pectus defects, joint laxity, craniosynostosis, arachnodactyly, scoliosis, talipes equinovarus, camptodactyly and malar hypoplasia. Some have dural ectasia. Additional features may include uterine, spleen or bowel rupture, thin, translucent, hyperextensible or velvety skin with atrophic scars and easy bruising. Blue sclera and a bifid uvula have also been observed.

Loeys-Dietz syndrome, type 1C (LDS1C; MIM 613795), also known as aneurysms-osteoarthritis syndrome (AOS), is an autosomal dominant disorder caused by mutations in the SMAD3 gene. SMAD3 is an important molecule in the TGFβ pathway. LDS1C/AOS is characterized by cardiovascular, joint and skeletal anomalies. Cardiovascular findings include frequent aneurysms or dissections of the thoracic and abdominal aortas, as well as the carotid, basilar ophthalmic, coronary, iliac, superior mesenteric, vertebral, pulmonary and splenic arteries. Arterial tortuosity of the thoracic, abdominal and cerebral arteries may also be present. Other findings may include mitral valve abnormalities, atrial fibrillation, and left ventricular hypertrophy. Painful joints, early onset osteoarthritis, intervertebral disc degeneration, irregularly shaped vertebral bodies, spondylysis and/or spondylolisthesis, non-traumatic osteochondritis dissecans and meniscal lesions are common. In one study, joint complaints represented the primary presenting symptoms. The most common skeletal findings include pes planus, scoliosis, pectus carinatum or excavatum, long slender fingers and protrusion acetabulae. Abnormal palate and uvula, velvety skin, striae, varices, umbilical hernia, inguinal hernia and easy bruising are also frequent. SMAD3 mutations are estimated to be responsible for about 2% of LDS1C/AOS cases. Penetrance is considered to be almost 100% but expression is variable.