A reappraisal of the clinical spectrum of North Carolina macular dystrophy

Ophthalmology. 2009 Oct;116(10):1976-83. doi: 10.1016/j.ophtha.2009.03.028. Epub 2009 Jul 18.


Purpose: To characterize the clinical phenotypes and genotype of a large family with North Carolina macular dystrophy (NCMD).

Design: Observational, retrospective case series.

Participants: Thirteen participants who were at risk of inheriting a dominantly transmitted disease gene from a 4-generation family from Baltimore were examined.

Methods: Thirteen participants underwent ophthalmic examination and genomic linkage analysis. Fundus photography, spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography, ultrasonography, full-field electroretinography, and electro-oculography were performed on some patients.

Main outcome measures: Description of clinical phenotypes with genomic linkage to the MCDR1 locus.

Results: Nine of 13 participants were affected with NCMD. There are variable and previously unreported clinical manifestations among affected individuals with NCMD, including drusen, macular staphyloma, choroidal neovascularization, a retinal pigment epithelial tear, and geographic atrophy. The distinctive and virtually pathognomonic grade 3 lesions in NCMD are neither staphylomas nor colobomas, as previously thought. As shown by ultrasonography and SD-OCT, they are deep chorioretinal excavations not involving the sclera, for which the authors propose a new term: macular caldera. Linkage analysis was performed, and the disease-causing gene in this family was mapped to the MCDR1 locus.

Conclusions: North Carolina macular dystrophy has a wide spectrum of clinical phenotypes that resemble age-related macular degeneration except for their early age of onset.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Baltimore
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 6 / genetics*
  • Electrooculography
  • Electroretinography
  • Eye Proteins / genetics*
  • Female
  • Fluorescein Angiography
  • Genetic Linkage
  • Genotype
  • Humans
  • Macular Degeneration / genetics*
  • Macular Degeneration / pathology*
  • Male
  • Middle Aged
  • North Carolina
  • Pedigree
  • Phenotype
  • Photography
  • Retrospective Studies
  • Tomography, Optical Coherence
  • Visual Acuity
  • Young Adult


  • Eye Proteins
  • MCDR1 protein, human