Customize your JAMA Network experience by selecting one or more topics from the list below.
Optic nerve aplasia is a rare developmental anomaly characterized bythe congenital absence of the optic nerve, retinal blood vessels, and retinalganglion cells.1-3 Opticnerve aplasia seems to fall within a malformation complex that is fundamentallydistinct from optic nerve hypoplasia, as evidenced by its tendency to occurunilaterally and its frequent association with microphthalmos and other malformationsthat are confined to the involved eye.3,4 Unilateraloptic nerve aplasia is generally associated with otherwise normal brain development,while bilateral optic nerve aplasia is usually accompanied by other centralnervous system derangement.4 To our knowledge,optic nerve aplasia has not been associated with endocrinologic deficiency.This report describes congenital hypopituitarism and posterior pituitary ectopiain an infant with bilateral optic nerve aplasia.
Report of a Case
A male infant was born to nonconsanguineous parents at 38 weeks' gestationwith a birth weight of 2750 g. There was no family history of microphthalmosor coloboma. The mother had a history of hyperthyroidism, which was treatedin late pregnancy with propothiouracil. Both of the child's eyes were notedto be small at birth, but no other systemic anomalies were observed. The newbornscreen showed a total thyroxine level of 4.1 µg/dL (53.0 nmol/L) (normalrange, 11-23 µg/dL [142-296 nmol/L]) and an initial serum glucose levelof 28 mg/dL (1.6 mmol/L). The patient required intravenous dextrose to maintaina normal serum glucose level. At 4 days of age, magnetic resonance imagesof the brain disclosed posterior pituitary ectopia with absence of the opticnerves, chiasm, and pituitary infundibulum (Figure 1). Endocrinologic testing at 1 week of age showed a freethyroxine level of 0.7 ng/dL (9.0 pmol/L) (normal range, 0.7-1.9 ng/dL [9.0-24.0pmol/L]), a late afternoon serum cortisol level of 3 µg/dL (77 nmol/L)(normal range, 4-11 µg/dL [110-304 nmol/L]), and a random growth hormonelevel of 4 ng/mL (185 pmol/L) (normal level > 10 ng/mL [>440 pmol/L]). Aninsulin-like growth factor I/somatotropin C level obtained 2 months laterwas 14 ng/mL (normal range, 17-248 ng/mL). Based on the severe hypoglycemia,low anterior pituitary hormone levels, and posterior pituitary ectopia, supplementationwith growth hormone, thyroxine, and hydrocortisone was initiated.
T1-weighted sagittal magneticresonance image showing ectopic posterior pituitary gland (solid arrow) andabsence of the pituitary infundibulum (open arrow denotes normal positionof infundibulum).
The patient had no behavioral response to light shined into either eyeduring an ophthalmologic examination at 2 months of age. Both palpebral fissureswere small, and there was bilateral microphthalmos. The corneas were clear,with a corneal diameter of 4 mm OD and 9 mm OS. The pupils were fixed, round,and nonreactive to light. The retina of the right eye could not be visualized.The left eye showed absence of the left optic nerve and central retinal vesselsduring indirect ophthalmoscopy (Figure 2).Numerous large, round, circumscribed, whitish areas of retinochoroidal depigmentationwere dispersed throughout the retinal periphery. Examination of both parentsdisclosed normal-sized eyes without evidence of colobomas.
Fundus photograph of the patient'sleft eye showing absence of the optic nerve and retinal vascular circulation,with a cluster of aberrant vessels occupying the normal position of the opticdisc (arrow).
Peripheral blood chromosomes were normal at 450-band resolution. Polymerasechain reaction amplification and sequencing of the coding regions and nearbyflanking sequences of the SIX6 (formerly OPTX2) homeobox gene, a developmental regulatory gene that is a candidategene for oculopituitary disorders,5 showedno mutations or amino acid sequence variants.
Posterior pituitary ectopia is a neurohypophyseal malformation thatis visible on T1-weighted magnetic resonance images as a hyperintense midlinenodule localized at or near the tuber cinereum.6 Itis usually accompanied by absence of the pituitary infundibulum and absenceof the normal posterior pituitary bright spot.6 Whilethis ectopic cluster of posterior pituicytes still functions as a normal posteriorpituitary gland, the associated absence of the pituitary infundibulum portendsa potentially life-threatening anterior pituitary hormone deficiency.6 Posterior pituitary ectopia can be seen in patientswith optic nerve hypoplasia or as an isolated malformation.6 Ina recent study of children with optic nerve hypoplasia, Phillips et al6 found posterior pituitary ectopia or absence ofthe pituitary infundibulum in 23 of 26 patients with congenital hypopituitarismvs none of the 41 patients with normal endocrinologic function.
To our knowledge, isolated optic nerve aplasia with hypopituitarismhas not been described. However, the association of optic nerve aplasia andhypopituitarism is well recognized in the clinical context of severe microphthalmosand anophthalmos (a condition in which the optic nerves are absent or rudimentary).7,8 Keppen et al7 foundhypogonadotropic hypogonadism in 5 of 13 patients with mental retardationand anophthalmos or severe microphthalmos, suggesting a generalized defectin forebrain development. Brodsky and Frindick8 documenteda neurohypophyseal malformation closely resembling posterior pituitary ectopiain a male infant with bilateral anophthalmos and low serum cortisol and pituitarygonadotropin levels. Neuroimaging results showed our patient's central nervoussystem abnormalities were confined to the anterior visual pathways and pituitaryinfundibulum. The risk of sudden death from addisonian crisis in childrenwith corticotropin deficiency mandates early recognition of congenital hypopituitarismin high-risk patients.9 Posterior pituitaryectopia may prove to be a neuroimaging marker for congenital hypopituitarismin children with optic nerve aplasia.
The authors have no relevant financial interest in this article.
This study was supported in part by a grant from Research to PreventBlindness Inc, New York, NY.
Corresponding author and reprints: Michael C. Brodsky, MD, ArkansasChildren's Hospital, 800 Marshall, Little Rock, AR 72202 (e-mail: firstname.lastname@example.org).
Brodsky MC, Atreides SA, Fowlkes JL, Sundin OH. Optic Nerve Aplasia in an Infant With Congenital Hypopituitarism andPosterior Pituitary Ectopia. Arch Ophthalmol. 2004;122(1):125–126. doi:10.1001/archopht.122.1.125
Create a personal account or sign in to: