Alex V. Levin
• Congenital hyperpigmented lesions of the fundus are differentiated based on appearance, pattern, and distribution in the ocular fundus and are present at birth.
• Includes: Grouped pigmentation (bear tracks), congenital hypertrophy of retinal pigmented epithelium (CHRPE), combined hamartoma of the retina, choroidal nevi, melanocytoma, chorioretinal scar (usually associated with hypopigmentation)
• Grouped pigmentation: 1.2/100 (3)
• Congenital hypertrophy of Retinal pigmented epithelium (CHRPE): 5 per 1,000 (3)
• Combined hamartoma of the retina: Precise frequency in the general population is unknown (3)
• Choroidal nevi: 10–13 per 100 (4)[B]
• Melanocytoma: Frequency in population is generally unknown (4)[B]
• Chorioretinal scar due to in utero toxoplasmosis: 1 in 10,000 live births (3)
• CHRPE: Family history of Gardner syndrome (adenomatous polyposis coli)
• Combined hamartoma of the retina and RPE: Family history of neurofibromatosis 2
• CHRPE lesions associated with mutations in the adenosis polyposis coli gene (APC, 5q21, autosomal dominant) if bilateral or >2 in one eye
• Combined hamartoma of the retina and RPE is associated with mutations in the gene for NF2 (22q12.2, autosomal dominant)
Genetic counseling (1,3) [B,C]
• Hyperpigmentation arises either from the neuroectodermal derived RPE or from melanocytes (neural crest) in the choroid
– Grouped pigmentation, CHRPE, and combined hamartoma arise from RPE
– Choroidal nevi arise from melanocytes in the choroid
– Melanocytoma is a benign optic nerve tumor of melanocytes with abundant melanin
• Migration and distribution of pigment containing cells may be dysfunctional during fetal development
• Pigment-containing cells may be altered genetically and by systemic and external stimuli (e.g., trauma, infection)
• Mutated or abnormal genes (1,3)[B,C]
• Inflammatory/infectious conditions causing chorioretinal scar
COMMONLY ASSOCIATED CONDITIONS
• CHRPE: Gardner Syndrome and Turcot Syndrome (adenomatous polyposis coli, tumors of the brain and spinal cord)
Combined hamartoma of the retina and RPE is associated with iris hamartoma: Manifestations of NF2 include acoustic neuromas, meningiomas of the optic nerve, and presenile posterior polar cataracts.
• Melanocytomas can be associated with iris melanocytomas, pupillary disfunction and corectopia, and secondary glaucoma (from spontaneous necrosis with the resultant pigment dispersion) (1,5)[B,C]
• Chorioretinal scar can be a manifestation of intrauterine infection, which may also affect central nervous system
• History of prenatal infections (2)
• Family history of colon cancer, NF2
• History of sarcomas, neurofibromas (1,2)[B,C] History about seizures, learning disabilities, and mental retardation
• For chorioretinal scars inquire about maternal history of ingestion of contaminated raw or undercooked beef, lamb, or pork, blood transfusions, organ transplants, or exposure to cats.
Full ocular examination including visual acuity, visual field testing (if age permits), and dilated funduscopic exam (3,4)[C,B].
DIAGNOSTIC TESTS & INTERPRETATION
Initial lab tests
Follow-up & special considerations
• Genetic consult if genetic syndrome (2)
• Choroidal nevi and melanocytoma require serial follow-ups (4)[B] and photo imaging for risk of malignant potential or advancement of disease.
• Colonoscopy beginning at the age of 8 years if Gardner syndrome
• Serial audiology if NF2
• If combined hamartoma associated with NF2, MRI of brain
– B-Scan and OCT may be used to evaluate hyperpigmented lesions
Molecular genetic testing as appropriate and available (2)[C].
Amblyopia therapy as indicated (1)[B]
Issues for Referral
• If Gardner syndrome suspected: Gastroenterology (2)
• If NF2 suspected: Otorhinolaryngology and Neurosurgery (2)
• Activation of toxoplasmosis chorioretinal scar: Consider Infectious Disease consultation
• Progression of choroidal nevus or melanocytoma require referral to an Ocular Oncologist
Choroidal nevi and melanocytoma: Photo documentation and serial examination (4)[B]
• Visual acuity
• Photo documentation of tumor growth for potential malignant transformation
• Genetic counseling
• Visual acuity and low vision intervention as indicated
– Report concerns regarding hearing or neurologic change if NF2
1. Ellis FD. Selected pigmented fundus lesions of children. J AAPOS 2005;9(4):306–314.
2. Lee DA, Higginbotham EJ. Clinical guide to comprehensive ophthalmology. New York: Thieme New York, 1999:478–485.
3. Taylor D. Paediatric ophthalmology. Oxford: Blackwell Science Ltd, 1990:122–143, 153–154, 587–598, 614–620.
4. Shields CL, Furuta M, Mashayekhi A, et al. Clinical spectrum of choroidal nevi based on age at presentation in 3422 consecutive eyes. Ophthamology 2008;115(3):546.e2–552.e2.
5. Yanoff M, Duker JS. Ophthalmology, 3rd ed. New York, NY: Mosby, 2008:511–516, 552–554, 935–936.