Cloverleaf skull syndrome, first described as the Kleeblattschädel deformity, is a rare craniofacial deformity caused by synostosis of multiple cranial sutures. The head is shaped like a clover leaf with a very constricted cranium and very prominent temporal bones. The prognosis for neurological outcome and cosmesis is poor unless early craniofacial surgery for decompression and reconstruction is carried out.^sup 1-2^ Survival is reduced and death in infancy due to the complications of raised intracranial pressure and brain compression is common.
We report the clinical and pathological findings of an eye enucleated from an 8-month-old infant with cloverleaf skull syndrome who died despite early surgical intervention. The patient was a full-term girl born to a 29year-old primigrávida. The infant had a tri-lobed skull, gross proptosis, marked lid retraction, conjunctival chemosis, and corneal opacities (Fig 1). X-rays and computed tomography (CT) scans showed fusion of the coronal, saggital, and lambdoidal skull sutures with evidence of hydrocephalus and vertebral anomalies. Corneal exposure was managed with hourly lubricants, topical antibiotics, gel foam, and topical Healon.
Fig 1: This photograph shows luxated globes with conjunctival chemosis and corneal exposure due to gross orbital shallowing in the infant with cloverleaf skull syndrome.
At 5 days of age, she underwent a radical suture release with advancement of the fronto-orbital skeleton via a transcranial approach. The periorbital tissues were released and the lids brought from their retracted position. A tarsorrhaphy was performed to treat corneal exposure and perforation. The right eye was later enucleated. At 1 month of age, a ventriculoperitoneal shunt was performed to treat hydrocephalus. She suffered recurrent episodes of apnea and bradycardia and died at 8 months of age.
On gross examination, the eye had an opaque, vascularized cornea with a diameter of 9 mm. There was a central white plaque on the cornea and a limbal scar. The cornea was thickened, the eye was aphakic, and the anterior chamber angle was closed. On microscopy, there was evidence of recent corneal ulcération with absence of Bowman's membrane, stremai fibrosis, and calcification.
A full-thickness stromal scar, surrounded by calcified material and adjacent foreign body giant cells, was present at the limbus. Peripheral anterior synechiae, angle recession, and closure were present. The eye was aphakic. Several patches of sectoral atrophy of the photoreceptor layer were present. There was focal dilatation proliferation of choroidal, ciliary body, and iris vessels and proliferation of vessels within the optic nerve, as shown in Fig 2. The optic nerve had a hypoplastic/atrophic appearance. In the peripapillary sclera, a depression contained primitive neural tissue (Fig 3).
Fig 2: This photomicrograph illustrates dilated vascular channels, some containing red blood cells, within the optic nerve. (Original magnification x10).
Fig 3: This illustrates an intrascleral peripapillary cavity containing primitive neurological tissue. The optic nerve is seen in the upper right hand corner of the micrograph. (Original magnification X4).
Cloverleaf syndrome is a craniosynostosis associated with midfacial hypoplasia and exophthalmos.3*4 Like other craniosynostoses, the condition is present at birth and continues to progress until the child is 2 to 3 years old. Ophthalmic involvement is a major feature of this syndrome.5 The most severe problem is exposure keratitis, secondary to severe proptosis or luxation of the globe. Typically, the orbits are shallow with reduced anteroposterior length, resulting in partial dislocation of the normally growing eye ball.
It is theorized that pressure in the anterior cranial fossa limits superior orbital growth and depresses the cribriform plate, displacing the ethmoid bones laterally, while maxillary hypoplasia produces a shortened orbital floor. Hypertelorism is due to the lateral displacement of the ethmoids. Exposure keratitis is managed by intensive lubrication, tarsorrhaphy and, if the globe is luxated anterior to the eyelids, by release of the periorbital tissues and surgical enlargement of the orbital cavity.
In this patient, despite early intensive management, corneal perforation occurred. The presence of the healed full-thickness limbal scar with extensive calcification, as well as the recent perforation, suggests that the fetus may have sustained in útero corneal perforation, which healed with dystrophic calcification. It is possible that the lens was extruded in utero.
Either optic atrophy or optic nerve hypoplasia was present, a common finding in the craniosynostoses.p 6 Other abnormalities that have been reported include nasolacrimal duct obstruction and colobomata.p 7 Additional findings in this case include vascular proliferation of the anterior and posterior uveal tract, a peripapillary depression containing primitive neural tissue, and sectoral atrophy of the photoreceptor layer of the retina.
This case highlights the clinical and pathological features of interest to the ophthalmologist in this rare, lifethreatening syndrome.
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