Hippel-Lindau disease (Hippel-Lindau): causes, symptoms, diagnosis, treatment

Angiomatosis of the retina and cerebellum constitute a syndrome known as von Hippel-Lindau disease. The disease is inherited in an autosomal dominant manner. The gene responsible for the syndrome is located on the short arm of chromosome 3 (3p25-p26). The main features of the disease include angiomatosis of the retina, hemangioblastomas of the cerebellum, brain and spinal cord, as well as renal carcinomas and pheochromocytomas.

A characteristic feature of this disorder is the diversity of clinical symptoms. Rarely do all pathological signs of the disease appear in one patient.

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Symptoms of Von Hippel-Lindau disease

Neurological

Damage to the central nervous system is almost always localized below the tentorium cerebelli. The most common is cerebellar hemangioblastoma, occurring with a frequency of about 20%. Similar damage occurs in the brain and spinal cord, but more rarely. Syringobulbia and syringomyelia may be observed.

Lesions of internal organs

The kidneys are involved in the pathological process with the formation of carcinomas or hemangioblastomas from parenchymatous cells. Less frequently, hemangioma of the pancreas occurs. Pheochromocytomas are observed in approximately 10% of patients. Epididymal paraganglioma is not characteristic of von Hippel-Lindau syndrome.

Ophthalmological manifestations

Approximately 2/3 of all cases of the disease involve retinal angiomatosis, usually localized in the middle periphery. Five stages of development of this damage have been described.

• Stage 1. Preclinical; initial accumulations of capillaries, their slight expansion according to the type of diabetic microaneurysms.
• Stage 2. Classical; formation of typical retinal angiomas.
• Stage 3. Exudative; caused by increased permeability of the vascular walls of angiomatous nodes.
• Stage 4. Retinal detachment of an exudative or tractional nature.
• Stage 5. Terminal stage; retinal detachment, uveitis, glaucoma, phthisis of the eyeball. Treatment started at the early stages of the disease is associated with a lower risk of complications. Cryo-, laser- and radiation therapy, as well as surgical resection are possible.

Screening of patients with Von Hippel-Lindau syndrome is necessary, including the following studies:

1. annual inspection with registration of the data obtained;
2. ophthalmological examination every 6-12 months starting at age 6;
3. at least one urine test for pheochromocytoma and repeat testing if blood pressure is elevated or unstable;
4. bilateral selective angiography of the kidneys when the patient reaches 15-20 years of age, with the procedure repeated every 1-5 years;
5. MRI of the posterior cranial fossa;
6. Computed tomography of the pancreas and kidneys when the patient reaches 15-20 years of age, with the procedure repeated every 1-5 years or unscheduled when the corresponding symptoms appear. It is advisable to screen children from parents affected by the syndrome and/or other close relatives with a high risk of developing the disease. The study is carried out in the following areas:
   • examination with registration of the data obtained upon the child reaching 10 years of age;
   • annual ophthalmological examination starting from the age of 6 or when suspicious symptoms appear;
   • at least one urine test for pheochromocytoma and repeat testing if blood pressure is elevated or unstable;
   • MRI of the posterior cranial fossa, CT of the pancreas and kidneys upon reaching the age of 20;
   • ultrasound examination of the pancreas and kidneys after 15-20 years of age;
   • If possible, a family history test to determine which family members carry the gene responsible for the syndrome.