retinal angioma

Cerebral Cavernous Malformations

Clinical Characteristics
Ocular Features: 

Cavernous capillary hemangiomas usually occur singly in the fundus, often at the disc.  Fewer than 5% of individuals with CCM have retinal lesions.  As opposed to the systemic hemangiomas, those in the eye tend to be stable.  However, they may result in vitreous hemorrhages because they lack the usual structural support of normal vessels.  Fluorescein angiography often reveals blood-fluid levels in the saccules that comprise the grape-like cluster of the tumor.

Systemic Features: 

Cavernous angiomas may involve any part of the CNS, brain stem, and spinal cord.  These are benign aberrant growths of capillary endothelium which develop shortly after birth and cause a variety of signs and symptoms including seizures, intracranial hemorrhage, and focal neurologic deficits. New lesions can appear throughout life. The blood –containing clusters are lined with endothelium only and the walls lack muscle or fibrous tissue.  Up to 25% are diagnosed in children. They may be angiographically silent but MRI is diagnostically useful.  Cutaneous hemangiomas are uncommon but helpful diagnostically when present.  The overlying skin may be hyperkeratotic.

Many patients (25-50%) remain asymptomatic throughout life.

Genetics

This is an autosomal dominant disorder caused by mutations in three genes.  CCM1 (116860) results from mutations in the KRIT1 gene located at 7q11.2-q21, the disease called CCM2 (603284) is caused by mutations in the CCM2/malcavernin gene (7p13), and CCM3 (603285) by mutations in the PDCD10 gene at 3q26.1.  The majority of familial cases have mutations in one of these genes.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

The fundus lesions seldom require treatment but photocoagulation can be used to seal those that lead to recurrent vitreous hemorrhages.  Embolism may be beneficial for CNS lesions but the lesions in many locations are relatively easy to remove surgically. Seizures are treated symptomatically.  Pharmaceutical agents that alter blood clotting should be administered with careful monitoring.

References
Article Title: 

Genotype-phenotype correlations in cerebral cavernous malformations patients

Denier C, Labauge P, Bergametti F, Marchelli F, Riant F, Arnoult M, Maciazek J, Vicaut E, Brunereau L, Tournier-Lasserve E; Soci?(c)t?(c) Fran?ssaise de Neurochirurgie. Genotype-phenotype correlations in cerebral cavernous malformations patients. Ann Neurol. 2006 Nov;60(5):550-6.

PubMed ID: 
17041941

Von Hippel-Lindau Syndrome

Clinical Characteristics
Ocular Features: 

Retinal angiomas are a feature of this syndrome, occurring in up to 70% of patients and often diagnosed by about age 25 years.  These hemangioblastomas are often connected to prominent arterioles and venules indicative of their vascular nature.  Capillary hamartomas located on or near the optic nerve may mimic papilledema or papillitis.  However, they may also occur throughout the retina and visual morbidity often results from secondary damage due to hemorrhage, exudates, and traction on the retina. When they are bilateral and multicentric the diagnosis of VHL is highly likely.  Patients with VHL tend to develop such tumors at a younger age and have worse visual outcomes than those in patients without VHL.  The impact on vision is responsible for initial presentation in many patients.

Systemic Features: 

Clinical symptoms typically have their onset during the second decade of life.  These commonly (in 35% of patients) result from the presence of a cerebellar hemangioblastoma while overall more than 60% eventually develop this malignancy.  Up to 40% of patients develop renal cell carcinomas and these are a major cause of death.   However, benign and malignant tumors may appear in many organs including the adrenal glands, pancreas, and spinal cord.  Pheochromocytomas occur in 20-35% of individuals and may be bilateral and multifocal.  These can induce an erythrocythemia. Endolymphatic sac tumors occur in about 10% of patients.  Cystic lesions are often associated with the tumors, especially in the pancreas.

Several subtypes have been proposed based on the pattern of malignancies and the types of mutations found in patients.

Genetics

This is an autosomal dominant cancer susceptibility disorder caused by a mutation in the VHL gene located at 3p26-p25.

There is evidence that the phenotype can be modified by variations in the cyclin D1 gene (CCND1) located at 11q13.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Local excision of isolated lesions can be considered in selected cases.  Photocoagulation and cryotherapy of retinal hamartomas can be considered although outcomes are variable depending on location and size of the lesions.

References
Article Title: 

A genetic register for von Hippel-Lindau disease

Maddock IR, Moran A, Maher ER, Teare MD, Norman A, Payne SJ, Whitehouse R, Dodd C, Lavin M, Hartley N, Super M, Evans DG. A genetic register for von Hippel-Lindau disease. J Med Genet. 1996 Feb;33(2):120-7.

PubMed ID: 
8929948

Genetic analysis of von Hippel-Lindau disease

Nordstrom-O'Brien M, van der Luijt RB, van Rooijen E, van den Ouweland AM, Majoor-Krakauer DF, Lolkema MP, van Brussel A, Voest EE, Giles RH. Genetic analysis of von Hippel-Lindau disease. Hum Mutat. 2010 May;31(5):521-37.

PubMed ID: 
20151405
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