Other Phacomatosis

Tuberous sclerosis (Bourneville's disease)

condition characterized by various forms of skin lesions caused by autosomal dominant mutation of TSC genes located on chromosomes 9 AND 16 (both mutations required).

2

Mutations of the TSC (1 or 2) gene are more common (50%) and produce more severe disease

66%

percentage of tuberous sclerosis cases that are due to spontaneous mutation

Ash leaf spots

hypomelanotic areas of the skin present in 90% of patients having tuberous sclerosis

Adenoma sebaceum

angiofibromas of the skin presenting as a reddish brown papular rash in 75% of patients having tuberous sclerosis

25

Fibromas of the nail occur in ______% of patients having tuberous sclerosis

Shagreen patches

connective tissue hamartomas occurring in 20% of tuberous sclerosis patients typically in the lumbosacral region.

RPE depigmentation

Angiofibromas of the lid and conjunctiva

2 Ocular Findings in Tuberous Sclerosis

Lung complications

Renal complications (cysts, carcinoma)

Rhabdomyosarcoma (67%)

Spinal sclerosis (40%)

Pitting of tooth enamel

5 Systemic Considerations of Tuberous Sclerosis

2, 1, 2

The definite diagnosis of tuberous sclerosis involves the identification of ____ major features, or ____ major and ____ minor features

1

The possible diagnosis of tuberous sclerosis involves the identification of ___ major feature and ____ minor feature

Von Hippel Lindau disease

condition characterized by angiomatoses of the retina and cerebellum and renal cell carcinoma due to an autosomal dominant mutation of the 3p25-26 tumor suppressing gene. Does not involve cutaneous lesions.

peripheral

Retinal hemangioblastomas occurring in von Hippel Lindau disease occur in the _____ retinal

RD, glaucoma, persistent uveitis

patients having advanced retinal hemangioblastomas and Von Hippel Lindau disease experience blindness secondary to associated... (3)

50%

percentage of von Hippel Lindau patients that have bilateral retinal disease

60%

percentage of von Hippel Lindau patients that have multiple lesions in one eye

50%

percentage of von Hippel Lindau patients that will have severe vision loss if left untreated

Photocoagulation

Cryotherapy

Anti-VEGF injection

3 Treatments of Retinal Hemangioblastomas

cerebellum

Lesions of the CNS in Von Hippel Lindau disease typically occur in the...

Syrinx

fluid filled cyst of the spinal cord or brainstem occurring in Von Hippel Lindau disease. Presents as weakness, atrophy of hands and arms, pain, and nystagmus.

Endolymphatic sac tumors

aggressive tumors in Von Hippel Lindau disease that present with symptoms such as hearing loss, tinnitus, vertigo, and facial weakness.

-Renal cell carcinoma

-Pheochromocytoma

-Polycythemia

-Benign cysts of kidney, pancreas, liver, epididymis

4 Visceral findings in Von Hippel Lindau Disease

-CNS or retinal hemangioblastoma with a visceral manifestation

-Family history

-Presence of gene mutation

Diagnosis of Von Hippel Lindau Disease (3)

Sturge Weber Syndrome

condition characterized by capillary venous vascular malformation of the brain, meninges, and skin with an unknown inheritance pattern. Occurs due to a somatic mosaic mutation of G protein alpha subunit q (GNAQ).

CN V

Facial hemangioma seen in Sturge Weber syndrome is present at birth following the distribution of...

hemihypertrophy

Port wine stain may be associated with ____ of the face

60%

percentage of Sturge Weber patients that develop secondary glaucoma by the age of 2 yo. Is more common if the hemangioma involves the upper lid.

ipsilateral, patieto-occipital

Central nervous system hemangiomas in Sturge Weber syndrome usually occur _____ to the facial lesion located in the _____ area. The underlying cortex is maldeveloped with absent or non-functional veins and calcium deposition ("tram track")

Cortical seizures (75%)

Learning disability (55-85%)

Hemiplegia

VF deficits

Headaches

Growth hormone deficiency

6 Clinical Consequences of Sturge Weber Syndrome

-Facial angioma with ipsilateral intracranial hemangioma

-Ipsilateral choroidal hemangioma

-Congenital glaucoma

Diagnosis of Sturge Weber Syndrome involves at least 2 of these three diagnostic criteria

can

Patients (can or cannot) have a port wine stain in the absence of Sturge Weber syndrome

Wyburn mason syndrome (retinocephalic vascular malformation)

very rare condition characterized by arterio-venous malformations of the brain, retina, orbit, and skin.

Racemose angioma

Orbital AVM

Optic nerve AVM

3 Ocular Findings of Wyburn Mason Syndrome

ipsilateral, 50

Central nervous systemic AV malformations in Wyburn mason syndrome occur ____ to the retinal lesion with ____% of these patients having symptoms

intracranial with retinal AVM

Diagnosis of Wyburn mason syndrome involves...

Louis Bar syndrome (ataxia telangiactasia)

condition characterized by cutaneous lesions of the ears, nose, and antecubital fossae usually present around the age of 4 yo. Occurs due to autosomal recessive mutation of the AT gene (DNA damage repair) on chromosome 11.

Bilateral bulbar conjunctival telangiectasia

Ocular motility disturbances

2 Ocular Findings of Louis Bar Syndrome

3-6

Bilateral bulbar conjunctival telangiectasia in Louis bar syndrome

Appear at the age ____ yo and become more prominent with age

Complete supranuclear ophthalmoplegia

ocular motility disturbance in Louis bar syndrome ultimately progresses to...

10

Louis bar syndrome patients may become wheelchair bound by age ____ yo due to atrophy of the cerebellar cortex and vermis

Dysarthria

slurred speech due to loss of muscular control. seen secondary to CNS lesions of Louis bar syndrome

Chorea

involuntary fidgety muscle movements. seen secondary to CNS lesions of Louis bar syndrome

Dystonia

involuntary muscle contractions. seen secondary to CNS lesions of Louis bar syndrome

IgG2, IgG4, IgA, IgE

4 immunoglobulins that are deficient in Louis bar syndrome

100

patients with Louis bar syndrome have a ____x the risk of cancer due to poor DNA repair

Alpha-fetoprotein

cancer marker that is elevated in Louis Bar syndrome patients

-Increased radiation induced chromosomal breakage in cultured cells

-Progressive cerebellar ataxia with mutations in both alleles

Definite Diagnosis of Louis Bar Syndrome requires 1 of these two findings

-Ocular or facial telangiectasia

-elevated Alpha-fetoprotein

-depressed IgA levels

Probable (3) and Probable (2) Diagnosis of Louis Bar Syndrome

(3 diagnostic findings)

Klippel-tranaunay weber syndrome (KTWS)

condition characterized by an overgrowth of tissue secondary to a mutation of the PIK3CA gene. Presents with cutaneous capillary malformations, varicosities, and tissue hypertrophy most commonly affecting the arms, trunk, head, and neck. Gait deformities and scoliosis may arise from abnormal bone and soft tissue hypertrophy.

98

Port wine stain that thickenings and darkens with age is seen in _____% of patients having Klippel-Tranaunay weber syndrome

Orbital varix

Iris heterochromia

Choroidal angioma

3 Ocular Findings of Klippel-Tranaunay Weber Syndrome

Cutaneous vascular abnormality

Soft tissue hypertrophy

Bony hypertrophy

Varicose veins

Diagnosis of Klippel-Tranaunay Weber Syndrome

(requires 2 of these four diagnostic criteria