Phakamatoses

Question 1

Racemose Angiomatosis

Answer 1

Bonnet Dechaume blanc syndrome
Wyburn-Mason syndrome

Retinal and midbrain AVM
Vessels do not leak

Inheritance / Chromosome?
Sporadic

Systemic findings?
Seizures
Mental changes
Hemiparesis
Intracranial calcifications

Question 2

encephalotrigeminal angiomatosos

Answer 2

Sturge-Weber syndrome
Inheritance / Chromosome? Sporadic

Eye findings?
Choroidal hemangioma (tomato catsup fundus)
Tx: PDT > laser, cryo, plaque/beam XRT

Dilated, tortuous conj vessels
Increased risk of choroidal effusion
Heterochromia (iris angiomas)
Glaucoma in 50%
Risk for massive hemorrhage during glaucoma surgery

Systemic findings?
Nevus flammeus (skin angioma)
(Meningeal hemangioma) leptomeningeal vascular malformations which lead to cortical/subcortical calcifications.
normal or mental retardation, hemiparesis
-stroke-like episodes assoc/w/ seizures and migraines.
-avoid contact sports that may result in any blows to the head.

Imaging findings?
Cerebral calcification on CT
DIFFUSE choroidal hemangioma (Circumscribed version has no association with S-W) = redder/pinker compared to the normal undus

Other key properties of SWS is:

(1) NOT genetically-transmitted (unlike the other 3 major phakomatoses)
(2) port-wine stain - the size of this birthmark positively correlates with the probability of CNS involvement
(3) secondary glaucoma (either from increased episcleral venous pressure [if presenting after age 10] or a primary angle abnormality [if presenting before age 10]) occurs on the side of the port-wine stain.

Question 2

Multiple Inherited Schwannomas, Meningiomas, and Ependymomas syndrome (MISME)

Answer 2

NF2

Question 4

Multiple Inherited Schwannomas, Meningiomas, and Ependymomas syndrome (MISME)

Answer 4

Neurofibromatosis Type 2 (NF2)
Inheritance / Chromosome? AD (Ch 22)

Neurological findings?
Bilateral acoustic neuromas
Meningiomas more common than in NF1

Eye findings?
PSC cataract
Wedge cortical cataract
Retinal hamartomas
Combined hamartomas of retina & RPE
Lisch nodules uncommon

Question 5

Retinal Angiomatosis

Answer 5

Von Hippel Lindau

Inheritance / Chromosome? AD (Ch 3)

Eye findings?
Retinal capillary hemangioma*
     (Feeder and drainage vessel)
     (Serous exudate may cause RD)
can also see VH/RD

Neurological findings?
Cerebellar hemangioma (primary cause of death)
(also brain stem, spinal cord)
No mental retardation

Associated tumors?
Pheochromocytoma, RCC (primary cause of death)

Treatment?
Laser, cryo of retinal angiomas

*capillary hemangioima (aka retinal hemangioblastoma) =
reddish-orange vascular tumor that is fed by a dilated, tortuous retinal artery and drained by an engorged vein. –can occur in both hereditary (autosomal dominant) and sporadic forms. Lesions in eye only (=von Hippel lesions), if CNS + visceral inv (von Hippel disease)

Question 6

Choroidal hemangiomas

Answer 6

Choroidal hemangiomas = benign vascular tumors that may arise as isolated lesions without other vascular malformations, or as diffuse thickening of the choroid in association with Sturge-Weber syndrome, a nonfamilial condition characterized by ipsilateral angiomatous lesions involving the face, brain, and uveal tract.

In contrast to melanomas, choroidal hemangiomas exhibit high internal reflectivity on A-scan echography. During fluorescein angiography, they fill during the prearteriole and arteriole phases, and leak during the late phases. Serous or lipid exudation accounts for loss of vision in many patients. Subretinal neovascular membranes rarely, if ever, develop from choroidal hemangiomas.

Question 7

Inheritance

Answer 7

Wyburn-Mason syndrome (aka “racemose angioma”) is also nonhereditary.

anything with “W” is without inheritance; i.e., sporadic
anything with “S” has seizures; e.g., TS, SWS

Question 8

Louis Barr syndrome

Answer 8

Ataxia-Telengectasia
Inheritance / Chromosome? AR (Ch 11)

By 2 yo: truncal ataxis f/u by dysarthria, dystonia, choreoathetosis.
Physically disabled by age 10.

Childhood onset of progressive cerebellar ataxia and oculocutaneous (conjunctival) telangiectasia (develop at 3-5 yo)

one of the EARLIEST signs in the entire body = impaired ability to initiate saccades.

Eye motility problem?
Supranuclear motility disturbances and eventual ophthalmoplegia

Oculocephalic response (dolls-eye maneuver)?
Intact

Cause of morbidity?
Thymic hypoplasia and immunosupression (decreased levels of IgG –> high prevalence of bacterial associated respiratory death in childhood)
Lymphoma and leukemia (esp T cell)

Gene defect = ATM (ataxia-telangiectasia mutated gene).
Nml gene = involved in repair of DNA and tumor suppression.

Female heterozygotes have increased risk of?
Breast CA (7x increased risk)

Question 9

von Recklinghausen disease

Answer 9

Neurofibromatosis Type 1 (NF1)
Inheritance / Chromosome? AD (Ch 17)

Criteria?
Café-au-lait spots (99% of patients) = 6+
Axillary freckling
Lisch nodules (iris hamartomas) appear b/t 5-10 yo = 2+
Bony Absence of sphenoid wing (pulsatile proptosis)
Optic nerve gliomas (common)
Relative affected (1st degree)
Neurofibromas (nodular) 2+ or 1 Plexiform neurofibromas (S-shape eyelid)

Other findings?
CNS gliomas
Increased risk of glaucoma (usu. Unilateral)
Astrocytic hamartomas
Combined hamartoma of the retina & RPE
Acoustic schwanomas

Associated tumors?
Pheochromocytomas, Wilms tumor

Question 10

Bloch-Sulzberger Syndrome

Answer 10

Incontinentia Pigmenti

Inheritance?
XD, female only (lethal for males)
Mother to daughter transmission

Skin lesions?
Hyperpigmented macules in “splashed paint” distribution on trunk

Other findings?
seizures, mental retardation, dental abnormalities

Eye findings?
Proliferative retinal vasculopathy with peripheral NV resembling ROP

Secondary consequences: microphthalmos, cataract, retrolental membrane, glaucoma, strabismus, nystagmus