CAM

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

Cataracts, Lamellar

Clinical Characteristics
Ocular Features: 

This type of heritable cataract is progressive and has a variable phenotype both within and between families.  It is usually seen bilaterally in early childhood but may be congenital in onset.  Fine, dispersed, pulverulent opacities of the primary lens fibers are seen in the embryonic nucleus often with increased density at the ends of the Y suture at 12, 2, and 6 o'clock presenting a triangular appearance.  However, the entire nucleus may be opaque as well.  Zonular and posterior subcapsular opacities may appear later but there is considerable variation among patients and they may also appear in a stellate pattern.  The lamellar pattern consists of a zone of opacification around a clear embryonic nucleus.  There may be considerable difference in the rate of progression of the opacities among patients and even between the two eyes.

This may be among the most common type of congenital, autosomal dominant cataract.  The first family was reported in 1878 and the family data has been updated and reported several times since then.  The most recent reported pedigree consisted of 965 individuals in 9 generations.  Among the 70 individuals added, 56 had cataract surgery performed between the ages of 1 month and 26 years with a mean of 8 years.  However, some adults never had cataract surgery. 

Another family with early onset, progressive, autosomal dominant cataracts mapping to the same locus has been reported (see Maumenee, 1979) but the opacification involves the secondary lens fibers at the posterior pole.  These may be variants of the same condition.

Systemic Features: 

This is a non-syndromal cataract disorder and no systemic disease has been associated.  

Genetics

This type of congenital cataract may be caused by mutations in the heat-shock transcription factor-4 gene (HSF4) located at 16q21-q22.1.  It is inherited in an autosomal dominant pattern. 

Another morphologically different autosomal dominant congenital cataract has been linked to the same locus (see Maumenee, 1979).

Other forms of autosomal dominantly inherited, congenital, progressive lens opacities include congenital cerulean (115660, 601547, 608983, 610202), Volkmann type (115665), Coppock-like (604307), and congenital posterior polar (116600) cataracts. Due to clinical heterogeneity, it is not always possible to classify specific families based on the appearance and natural history of the lens opacities alone.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Visually significant opacities require surgery. Amblyopia, if present, should be treated early.  

References
Article Title: 
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