Arterial Tortuosity Syndrome

Arterial tortuosity syndrome is a rare autosomal recessive connective tissue disorder caused by SLC2A10 variants, with elongation, tortuosity and aneurysm of large and medium arteries. Presentation is in infancy or childhood, and arterial stenosis and aneurysm increase the risk of stroke, ischaemia and rupture.

Pathophysiology. SLC2A10 encodes the glucose transporter GLUT10, and loss of function raises TGF-beta signalling and disrupts elastic fibre and extracellular matrix of the vessel wall. The consequence is an elongated, tortuous aorta and branch vessels that are stenosed or aneurysmal.

Consanguinity is common in reported families. Severity varies, and some infants with severe pulmonary artery stenosis do poorly.

Arterial imaging defines prognosis and drives surgery.

• Elongated face, beaked nose, micrognathia, high palate
• Soft hyperextensible skin and joint laxity
• Arterial tortuosity of aorta, carotid and cerebral arteries
• Aortic aneurysm, pulmonary artery stenosis, and stenosis of other major arteries
• Stroke, transient ischaemic attack, and dissection
• Keratoconus, hernia and diaphragmatic hernia
• Arachnodactyly, pectus deformity and scoliosis
• Hypotonia, and failure to thrive in severe infantile forms

• Genetic testing of SLC2A10 with deletion and duplication analysis; parental carrier testing.
• Vascular imaging: MR or CT angiography from head to pelvis to define tortuosity, stenosis and aneurysm, and echocardiography for aortic root and pulmonary arteries.
• Cerebrovascular imaging: MR angiography of intracranial vessels.
• Eye examination: corneal topography for keratoconus.
• Exclusion of other conditions with connective tissue panel including FBN1, TGFBR1, TGFBR2, SMAD3 and COL3A1.

Differential diagnosis.

• Loeys-Dietz syndrome
• Vascular Ehlers-Danlos syndrome
• Cutis laxa and fibulin related disorders
• Marfan syndrome
• Menkes disease
• Takayasu arteritis and fibromuscular dysplasia

• Medical therapy: a beta blocker or losartan to limit wall stress, for example atenolol 0.5 to 1 mg/kg orally daily (adults 25 to 100 mg daily), or losartan 0.4 to 1.4 mg/kg daily in children (adults 50 to 100 mg daily). Use in specialist care, and monitor blood pressure and renal function.
• Surgical and endovascular treatment: repair aneurysms in the aorta and large vessels by size and rate of growth, and treat symptomatic stenoses (pulmonary artery or aortic) by surgery or stenting. Operative planning must allow for fragile and tortuous vessels.
• Stroke prevention: careful control of blood pressure, avoidance of smoking, and antiplatelet therapy such as aspirin 75 mg once daily for patients with cerebrovascular disease (after specialist review).
• Activity advice: avoid contact sports and heavy isometric exertion.
• Drugs to avoid: fluoroquinolones and vasoconstrictors.
• Eye and hernia care: keratoconus management (cross-linking if progressive) and hernia repair with mesh.
• Genetic counselling: each sibling of an affected child has a 25% chance of being affected.

Special groups.

• Infants with severe pulmonary artery stenosis or heart failure need early cardiology care, and some need surgery.
• Pregnancy: high risk and specialist obstetric and cardiac planning.

Monitoring. Echocardiography every 6 to 12 months. Whole body MR or CT angiography at baseline and every 1 to 3 years, or sooner for symptoms. Annual eye review.

Referral and escalation. Refer to clinical genetics, paediatric cardiology and vascular surgery. Emergency for sudden neurological deficit, chest or abdominal pain, or limb ischaemia.