Phakomatoses are a multidisciplinary category of systemic diseases that is often tested for a multitude of reasons. Although the incidence of these conditions is fairly low (though chances are you will see at least 1 case of many of these conditions), there are many ocular findings that need to be considered.
I've been debating how to organize this information in a useful manner for review for quite some time. The subject material is pretty massive, and each condition could easily take several articles (and probably eventually will). But I wanted to make sure there was a useful review out there on this subject before the written board exam, in case the test covers one of these conditions.
For this article, I'm going to organize the phakomatoses in a series of different tables/lists that can be used as quick references. If you all have any suggestions or requests for putting this information together, I'd be happy to add to this resource!
Phakomatoses (also spelled phacomatoses) are a collection of systemic diseases that consist of hamartomas of the skin, eye, and central nervous system.
This table lists all of the phakomatoses and some basic information about each. I will eventually create articles highlighting each individual disease.
Inheritance and Genetics
Tips For Remembering Genetics and Inheritance
Genetics and inheritance are facts that are definitely testable, and may be somewhat detailed (Example: What chromosome is associated with ___________?). Other questions may be more generic (Example: Which phakomatosis is inherited ________?). Here are some tips that can hopefully help you remember these facts:
- "Neurofibromatosis" and "von Recklinghausen" each contain 17 letters...and the NF1 gene is on chromosome 17.
- The neurofibromatosis type 2 gene (NF2) is found on chromosome 22 (2's rule).
- von Hippel-Lindau syndrome is abbreviated VHL...and the VHL gene is found on chromosome 3 (3 letters in VHL).
- Sturge-Weber syndrome, Klippel-Trenauany-Weber syndrome, and Wyburn-Mason syndrome are inherited sporadically. The way I remembered this fact is that all three of these syndromes contain the letter W...and they are inherited "spoWadically" (cheesy but effective). Keep in mind that most cases of tuberous sclerosis arise de novo (implying sporadic inheritance).
- Ataxia-telangiectasia is inherited in an autosomal recessive pattern. Because the other name for ataxia-telangiectasia is Louis-Bar syndrome, I remember this fact because of the AR in Louis-BAR.
- Incontinentia pigmenti is one of 3 conditions that we have to know in ophthalmology that is inherited in a X-linked dominant pattern (the other two being Aicardi syndrome and Lisch corneal dystrophy). It's sufficiently unique that I just remember that fact.
- Everything else is inherited in an autosomal dominant pattern.
Sorry this turned out to be pretty long - I got pretty carried away with the comprehensiveness of the table - but I highlighted the more important information. The challenge is that there are so much important information to remember!
Tips For Remembering Ophthalmic Manifestations
- Each phakomatosis has at least 1 very distinctive ophthalmic manifestation. It's important to know those distinctive features, as you may be expected to recognize a condition simply from an image of one of those features.
- There are some secondary features that may be shared by several of the phakomatoses:
- Glaucoma may be seen in NF1, Sturge-Weber, Klippel-Trenaunay-Weber, and incontinentia pigmenti.
- Combined hamartoma of the RPE and retina may be seen in NF2 and incontinentia pigmenti.
- Cataracts may be seen in NF2 and incontinentia pigmenti.
- Strabismus may be seen in Sturge-Weber, Klippel-Trenaunay-Weber, ataxia-telangiectasia, and incontinentia pigmenti (noticing a pattern with incontinentia pigmenti?).
- Iris heterochromia may be seen in Sturge-Weber and Klippel-Trenaunay-Weber.
- Iris colobomas may also be seen in Sturge-Weber and Klippel-Trenaunay-Weber.
- Nystagmus may be seen in ataxia-telangiectasia and incontinentia pigmenti.
- Retinal astrocytic hamartomas may be seen in NF1 and tuberous sclerosis.
Tips For Remembering Cutaneous And Systemic Manifestations
- There are two phakomatoses associated with pheochromocytomas: NF1 and VHL. In residency, we remembered these as "von pheo," since both syndromes start with "von."
- Tuberous sclerosis and Sturge-Weber are associated with intracranial calcifications.
- Seizures may be seen in tuberous sclerosis, Sturge-Weber, Klippel-Trenaunay-Weber, Wyburn-Mason, and incontinentia pigmenti.
- Hyperpigmented macules may be seen in NF1 & NF2 (cafe-au-lait spots), tuberous sclerosis (cafe-au-lait spots), and incontinentia pigmenti ("splashed paint" spots).
References and Additional Reading
- Basic and Clinical Science Course, Section 6: Pediatric Ophthalmology and Strabismus. American Academy of Ophthalmology, 2015.
- Basic and Clinical Science Course, Section 12: Retina and Vitreous. American Academy of Ophthalmology, 2015.
- Kerrison JB. Phacomatoses. In: Miller N, Newman N, Biousse V, Kerrison JB, eds. Walsh and Hoyt's Clinical Neuro-Ophthalmology, 6th Ed. Philadelphia: Lippincott Williams & Wilkins, 2005.
- McLaughlin ME, Pepin SM, MacCollin M, et al. Ocular pathologic findings of neurofibromatosis type 2. Arch Ophthalmol. 2007;125(3):389-394. doi:10.1001/archopht.125.3.389.
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