Persistent hyperplastic primary vitreous (PHPV), a form of persistent fetal vasculature, occurs infrequently with systemic conditions.1 We report the novel association of unilateral PHPV with septo-optic-pituitary dysplasia (SOPD) and ipsilateral schizencephaly.
A full-term female neonate was born to a 17-year-old primigravid woman by cesarean delivery. On the third day of life, hypoglycemia and hypotonia raised the suspicion of sepsis, for which intravenous antibiotic therapy was administered. Microbiologic cultures were negative for organisms. The patient's condition stabilized and the neonate was discharged from the hospital.
On the ninth day of life, the patient was found ashen and unresponsive; she had suffered a grand mal seizure. On admission to a neonatal intensive care center, the patient was lethargic, hypotonic, hypoglycemic (1.270 mmol/L [23 mg/dL]), and hyperbilirubinemic (239.4 µmol/L [14.0 mg/dL]). Magnetic resonance imaging scans revealed an absent septum pellucidum, posterior ectopic pituitary gland, absent infundibulum, right closed lip schizencephaly, cortical dysplasia, and ventriculomegaly (Figure 1). Serum endocrinologic evaluation disclosed a low thyrotropin level (4.6 µIU/mL), low total thyroxine level (50 nmol/L [3.9 µg/dL]), low morning cortisol level (<55 nmol/L), and subnormal response to corticotropin stimulation (0.66 pmol/L). The patient was treated for thyrotropin deficiency and corticotropin deficiency with levothyroxine sodium and hydrocortisone, respectively.
T1-weighted magnetic resonance images of the head reveal persistent hyperplastic primary vitreous in the right eye (white arrowhead) (A); posterior ectopic pituitary gland (small arrow), absent infundibulum (large arrow), absent septum pellucidum (small white arrowhead) (B and C); and right closed lip schizencephaly (black arrowhead) (D).
During ophthalmic examination on the 13th day of life and again in the seventh week of life, the infant did not fixate but briefly followed light. Pupils sluggishly reacted to light and a left-sided beating nystagmus worsened on left gaze. Corneal diameters were 8 mm OD and 10 mm OS. Biomicroscopic examination of the right eye revealed a clear cornea, and a shallow, but formed, anterior chamber. Neither iris vessels nor elongated ciliary processes were noted. A fibrovascular plaque on the superonasal retrolental surface funneled to a vascular band that extended on to a small optic disc. Macular anatomy was absent in this eye (Figure 2).
A, Fundus photograph of the right eye shows persistent hyaloid artery extending on to a hypoplastic optic disc. B, Fundus photograph of the left eye shows enlarged retinal veins and a hypoplastic optic disc with double-ring sign.
The left eye was remarkable for a normal anterior segment, engorged retinal veins, and a small, pale optic disc with a double-ring sign. Because improvement in visual function with surgical intervention was not expected, only periodic follow-up was recommended.
Persistent hyperplastic primary vitreous refers to a form of persistent fetal vasculature in which the posterior tunica vasculosa lentis (or posterior fetal fibrovascular sheath) and the hyaloid artery fail to regress.1 Although traditionally a sporadic, unilateral, and isolated finding, PHPV also has been reported in trisomy 13, Norrie disease, Warburg syndrome, incontinentia pigmenti, cerebro-oculo-dysplasia-muscular dystrophy,1 and fetal alcohol syndrome.2 Malformations of the macula, such as hypoplasia in our patient, may occur.1
Septo-optic-pituitary dysplasia (de Morsier syndrome) refers to the variable constellation of absent septum pellucidum, complete or partial thinning of the corpus callosum, hypoplastic anterior visual pathways, and pituitary hormone deficiency.3,4 Endocrinologic problems may be life-threatening as in our patient, whose corticotropin deficiency caused apnea, hypotonia, seizures, prolonged jaundice, and hypoglycemia. Absent pituitary infundibulum on the magnetic resonance imaging scan correlates with concurrent endocrinologic deficiency, while an ectopic posterior pituitary, seen as an intense nodule in T1-weighted images, may have sparing of posterior pituitary function3 (Figure 1).
Schizencephaly is a cerebral hemisphere migration anomaly in which an abnormal gray matter– lined cleft extends through the cerebral hemisphere from the lateral ventricle to the cortical surface. Schizencephaly may accompany SOPD and can lead to seizure disorder and mental retardation.3
The pathogeneses of PHPV, SOPD, and schizencephaly are unclear. Persistent fetal vasculature has been postulated to be an arrest in fetal intraocular vascular development.1 Septo-optic-pituitary dysplasia has been postulated to result from supernormal regression of axons,4 disrupted migration of neurons and axons with failure to make target connections,3 or vascular insult to a developmental field during the first trimester of embryogenesis.5 Although a teratogenic history was not elicited in our patient, coincident optic nerve hypoplasia with PHPV2 and coincident SOPD and schizencephaly have been reported in patients with a maternal history of gestational substance abuse.5 Our case of unilateral PHPV with SOPD and ipsilateral schizencephaly is a novel and intriguing association.
This investigation was supported by unrestricted fund from the Research to Prevent Blindness Inc, New York, NY.
The authors have no proprietary interest in any material relating to this article.
Corresponding author: Andreas Katsuya Lauer, MD, Casey Eye Institute, Oregon Health Sciences Center, 3375 SW Terwilliger Blvd, Portland, OR 97201-4197.
Lauer AK, Balish MJ, Palmer EA. Persistent Hyperplastic Primary Vitreous Associated With Septo-optic-pituitary Dysplasia and Schizencephaly. Arch Ophthalmol. 2000;118(4):572-575. doi: