Genetic disorders: Loeys-Dietz syndrome

Loeys-Dietz syndrome (LDS) is a genetic disorder named after Dr. Bart Loeys and Dr. Hal Dietz at Johns Hopkins University School of Medicine. They were the first to describe the disorder in 2005. Because it is a newly recognized disorder and no two patients have the same physical manifestations of disease, the Loeys-Dietz Syndrome Foundation exists to aid patients and their doctors in finding support and treatment options.

The genetics of Loeys-Dietz syndrome

Based on Drs. Loeys and Dietz’s findings, deletions in two genes are known to be associated with LDS. The genes are TGFRB1 and TGFRB2. The disorder was found to be inherited in an autosomal dominant fashion, but only one-fourth of affected individuals have an affected parent. The other 75 percent of affected individuals have de novo mutations, meaning that the mutations occurred in the egg or sperm before fertilization or in the fertilized egg and were not inherited. An individual with LDS has a 50 percent chance of passing the mutation along to their child. Prenatal testing is available for the disorder, and diagnosis is mainly dependent on genetic testing.

Common features of LDS

According to Johns Hopkins, the majority of patients diagnosed with LDS tend to have abnormal craniofacial characteristics, such as widely spaced eyes and a large or double uvula. Drs. Loeys and Dietz differentiate between two types of LDS – three-quarters of patients have type 1 (with the craniofacial phenotype), and the other 25 percent have type 2 (with the cutaneous manifestation, including translucent skin, easy bruising and scarring problems). However, the two types have a continuum, so almost every patient with LDS has some cutaneous manifestion. A few patients with craniofacial manifestations have early fusion of the skull bones or cleft palate.

Both types of LDS have skeletal and vascular abnormalities. Skeletal deformities include scoliosis, cervical spine instability and deformity, sunken chest, long fingers, hypermobility of the joints (including hip dislocation at birth) and clubfoot. Like other connective tissue disorders, such as Marfan syndrome, the main concern with LDS is aortic dissection. The risk of this complication exists throughout the aortic root, even at smaller diameters. Dilation of the aortic root is present in 95 percent of LDS patients upon clinical diagnosis according to Drs. Dietz and Loeys. Half of LDS patients have an aneurysm distant from the aortic root.

Precautions for LDS patients

The progression of aortic aneurysms and dissection can be monitored by magnetic resonance angiography (MRA), computed tomography angiography (CTA) and regular echocardiography. Patients with Loeys-Dietz syndrome should avoid sports and isometric exercises, chemicals and pharmaceuticals that stimulate the cardiovascular system, and activities that cause joint pain. Endocarditis is a consideration for dental work, requiring preventative treatment to protect against infection and cardiovascular complications. Also, an orthopedist can address any spine stability issues.

Though this genetic disorder is relatively new, the two doctors for whom it is named uncovered a wealth of information about the syndrome, making it more discernible from other connective tissues disorders, like Marfan syndrome. Knowing what you’re up against helps your doctor determine the best treatment.