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A Possible New Genetic Syndrome

Emmett T. Cunningham, Jr, MD, PhD, MPH; Dean Eliott, MD; Neil R. Miller, MD; Irene H. Maumenee, MD; W. Richard Green, MD

Arch Ophthalmol. 1998;116:78-82.

Objective  To describe the clinical and ocular histopathological findings in multiple members of a family with congenital Axenfeld-Rieger anomaly, atrial septal defect, and sensorineural hearing loss.

Methods  We performed a retrospective review of the medical charts and the ocular histopathological material of multiple members of a family.

Results  Congenital Axenfeld-Rieger anomaly and glaucoma were inherited by both the proband and her male half-sibling from a phenotypically positive father and 2 different phenotypically negative mothers, suggesting an autosomal dominant inheritance. The proband's male half-sibling and her father also had atrial septal defects and sensorineural hearing loss. The proband's paternal grandmother had severe glaucoma. Histopathological analysis of blind, painful eyes removed from the proband's father and paternal grandmother showed incomplete development of the anterior chamber angle with iris stromal hypoplasia, prominent posterior embryotoxon with iris adhesions, and abnormal position and insertion of the ciliary muscles.

Conclusions  This is the first description of coexisting Axenfeld-Rieger anomaly, atrial septal defect, and sensorineural hearing loss in multiple members of a single family. The iris, trabecular meshwork, and large portions of the cardiac intraventricular septum all arise from neural crest anlagen, thus supporting the notion that anterior segment dysgenesis represents a developmental disorder of the neural crest.

From the Wilmer Ophthalmological Institute, the Johns Hopkins University Medical Institutions, Baltimore, Md. Dr Eliott is now affiliated with the Kresge Eye Institute, Wayne State University, Detroit, Mich.

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