Von Hippel Lindau Syndrome

Description

Von Hippel Lindau syndrome (VHLS) is one of the phakomatoses (“birthmarks”), the congenital or heritable conditions characterized by hamartomas and neoplasms throughout the body. The other phakomatoses include Neurofibromatosis, Sturge-Weber syndrome, Tuberous sclerosis, ataxia-telangiectasia and Wyburn-Mason syndrome. VHLS is inherited in an autosomal dominant pattern with incomplete penetrance, delayed expressivity and varied phenotypic expression. The affected gene is on chromosome 3.

VHLS is characterized by benign capillary hemangiomas (hamartomas), affecting the retina, CNS and other organs of the body. A hamartoma is a benign congenital tissue malformation made up of cells in their normal location but that are malformed or misarranged. Retinal capillary hamartomas may occur as an isolated entity (see Retinal Capillary Hemangioma), or in the VHLS where they are both systemic and ocular. Retinal hemangiomas tend to leak fluid, which may lead to the formation of exudates, hemorrhage and retinal detachment.

Symptoms

Retinal capillary hemangiomas may not cause symptoms and be detected at routine examination, or complications of the lesions may cause visual impairment. There may be a family history of VHLS.

Ocular Signs

Patients with VHLS typically have multiple retinal capillary hemangiomas, or single hemangioma with a family history of VHLS, as well as the systemic lesions. Retinal capillary hemangiomas initially appear as small red dots, usually in the mid-peripheral fundus. Over several years, they enlarge to become elevated, yellow-red tumors with a tortuous, dilated feeder artery and draining vein. Leakage of fluid, lipids and other blood components from larger tumors often results in the accumulation of hard exudates and subretinal fluid in a ring around the lesion. Other complications of advanced tumors include epiretinal membrane formation, retinal detachment and vitreous hemorrhage. See also: Retinal Capillary Hemangioma

Systemic Signs

Characteristic systemic findings may include:

• Central nervous system (especially cerebellar) hemangioblastoma and syringomyelia;
• Renal cell carcinoma;
• Pheochromocytoma;
• Cysts of the kidney, pancreas, epididymis and ovaries; and

Prevalence

Rare. VHLS occurs in less than 1 per 30,000 live births.

Significance

VHLS is a potentially fatal disease.

Differential Diagnosis

Coats’ Disease (Retinal Telangiectasia), Retinal Arterial Macroaneurysm, Retinoblastoma

See Also

Retinal Capillary Hemangioma, Retinal Detachment – Classification.

Management

Additional investigations

Evaluation for systemic capillary hemangiomas is commonly considered in the presence of multiple retinal capillary hemangiomas, or single hemangiomas in patients with a family history of VHLS. Magnetic resonance imaging (MRI) of the brain and spinal cord, and computed tomography (CT) scan of the abdomen may be indicated at approximately 3-year intervals. Annual physical and ocular examination, screening blood tests, urinalysis and renal ultrasound may also be indicated.

Genetics

Genetic assessment for the VHLS mutation may be advisable. Genetic counseling may be offered to affected families. Routine genetic screening of family members of patients carrying the VHLS mutation may be offered.

Laser and incisional surgery

For the management of ocular complications of VHLS see: Retinal Capillary Hemangioma.

Review

Lifelong follow-up care is indicated for VHLS since the disease is usually progressive. Ocular review may be indicated every 3 to 6 months depending on the retinal pathology.