Article

Cerebral Cavernous Malformations Associated With Cutaneous Angiokeratomas and Hemangiomas

Cutis. 2015 November;96(5):329-332

References

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Extracerebral manifestations of familial CCMs include retinal and cutaneous involvement. The incidence of retinal cavernomas has been estimated at 5% in familial CCM patients.¹⁷ The most commonly reported cutaneous finding (with an incidence of 3% to 5% reported in large case series) is hyperkeratotic cutaneous capillary-venous malformations (HCCVMs), which are composed of dilated capillaries and blood-filled, venouslike channels extending into the dermis and hypodermis with an overlying hyperkeratotic epidermis.^7,18-20 Although the prevalence for CCM1-associated CCMs is reported to be higher than that for the HCCVMs in families affected by both cerebral and cutaneous lesions, all patients manifesting HCCVMs also have CCMs.^18-20 Perhaps the cutaneous lesions may serve as markers of neurologic involvement in affected families. Other reports have shown an association between CCMs and cutaneous cavernous hemangiomas,²¹ capillary malformations,²⁰ venous malformations,^20,22 and cherry angiomas,^21,23 although the relevance of cherry angiomas is unclear given their high prevalence in the general population.

There are few reports of patients with CCMs having angiokeratomas, including a 77-year-old Hispanic man with a solitary angiokeratoma, cutaneous venous malformations, multiple CCMs, and demonstration of the 2105C→T CCM1 founder mutation, which is commonly found in Hispanic patients²⁴; a Chinese man with a CCM1 mutation and purple-black, raised, angiomalike skin lesions (similar to those seen in our patient) that which were not biopsied²⁵; and a patient with multiple eruptive angiokeratomas who was found to have numerous CCMs before the availability of genetic testing.²⁶ In our patient, the presentation of eruptive angiokeratomas prompted consideration of genetic testing and subsequent confirmation of a CCM1 mutation. Knowledge of the association between familial CCMs and cutaneous vascular lesions may be used to identify patients with clinically silent, undetected CCMs who may be at risk of developing future neurologic disorders or who may benefit from appropriate genetic counseling.

Conclusion

Familial CCMs are associated with extracerebral manifestations that include retinal cavernomas along with a variety of cutaneous manifestations. We present a case of a patient with adult-onset seizures, eruptive angiokeratomas, and cutaneous hemangiomas in the setting of numerous CCMs with confirmation of CCM1 mutation on genetic testing. We hope to raise awareness of the cutaneous findings associated with CCMs and the availability of genetic testing for CCM gene mutations so that patients with multiple cutaneous vascular lesions, including eruptive angiokeratomas, can be screened and tested for genetic mutations and neurologic involvement when appropriate.