Arterial tortuosity syndrome

Overview

Arterial Tortuosity Syndrome (ATS) is a rare, inherited connective tissue disorder characterized by marked elongation and tortuosity (twisting) of the large and medium-sized arteries throughout the body. This condition affects the structure and integrity of the blood vessel walls, making them more prone to aneurysms, stenoses, and other vascular complications.

ATS is considered part of the group of hereditary connective tissue diseases that include Marfan syndrome and Loeys-Dietz syndrome, but it has distinct clinical and genetic features.

Causes

ATS is caused by mutations in the SLC2A10 gene, which encodes the GLUT10 protein, a glucose transporter believed to play a role in vascular integrity and development. The condition is inherited in an autosomal recessive pattern, meaning a child must inherit one defective copy of the gene from each parent to develop the syndrome.

Mutations in SLC2A10 affect the structure and function of the connective tissue, especially elastin fibers in the blood vessel walls, resulting in arterial elongation, fragility, and abnormal curvature.

Symptoms

The clinical presentation of ATS varies, but hallmark features include:

Vascular Abnormalities:

• Generalized arterial tortuosity (twisting and elongation of arteries)

• Aneurysms and dissections (especially of the aorta and its branches)

• Arterial stenosis (narrowing), which may cause reduced blood flow

• Hypertension in some cases

Craniofacial and Skeletal Features:

• Elongated face

• Downslanting palpebral fissures

• Highly arched palate

• Joint hypermobility

• Pectus excavatum or pectus carinatum (chest wall deformities)

• Scoliosis or other spinal abnormalities

Other Possible Features:

• Hernias (inguinal or umbilical)

• Hyperextensible skin

• Delayed motor development in some children

• Respiratory difficulties due to tracheobronchial tortuosity

Diagnosis

Diagnosis of ATS involves a combination of clinical, radiological, and genetic investigations:

• Clinical evaluation: Recognition of characteristic craniofacial features and joint laxity

• Imaging studies:

  • Magnetic resonance angiography (MRA) or CT angiography (CTA): Reveal tortuous and elongated arteries

  • Echocardiography: To assess aortic root and detect aneurysms or valve issues

• Genetic testing: Identification of biallelic mutations in the SLC2A10 gene confirms the diagnosis

Treatment

There is no cure for ATS. Treatment focuses on monitoring and managing vascular complications and providing supportive care for associated features:

Cardiovascular Management:

• Regular imaging (e.g., MRA or CTA) to monitor for aneurysms, dissections, and stenoses

• Antihypertensive medications (e.g., beta-blockers or angiotensin receptor blockers) to reduce aortic stress

• Vascular surgery or stenting in cases of significant aneurysm or stenosis

Supportive Care:

• Orthopedic support for scoliosis or joint instability

• Physical therapy to improve strength and mobility

• Management of hernias and respiratory issues

Genetic Counseling:

• Recommended for families with affected children, especially if future pregnancies are planned

Prognosis

The prognosis of ATS depends largely on the severity and location of the vascular complications:

• With early diagnosis and careful monitoring, many individuals live into adulthood

• Severe vascular events such as aortic dissection or rupture can be life-threatening if not identified early

• Developmental delays and physical limitations may affect quality of life but are often manageable with therapy

Lifelong surveillance by a multidisciplinary team, including cardiologists, geneticists, and orthopedists, is essential to optimize outcomes and prevent complications.