From the Department of Ophthalmology (CA), The American University, Beruit, Lebanon; the Departments of Ophthalmology (M. Maybodi, M. Miller), Dermatology (RE), Pathology (RP), and Pediatrics (M. Miller), Children’s National Medical Center and The George Washington University, Washington, DC; and Cornea and Refractive Surgery (SB), The Washington Hospital Center and The George Washington University, Washington, DC.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Marijean Miller, MD, Ophthalmology and Pediatrics, The George Washington University, Children’s National Medical Center, 111 Michigan Avenue, Washington, DC 20010-2970.
This report describes a case of congenital symblephara, progressive corneal pannus, and skin defects caused by focal dermal hypoplasia, a disorder characterized by dysplasia of ectodermal and mesodermal tissue.1 Dermis, bones, and teeth can be involved in focal dermal hypoplasia. Ocular abnormalities include microphthalmia, corneal clouding, iris coloboma, ectopia lentis, choroidal coloboma, and strabismus.1
A female infant was born with thin-skinned hands and feet and absent urethral and vaginal openings. The parents were healthy with no history of consanguinity or eye disease. The mother had been prescribed nitrofurantoin, cephalexin, and promethazine during pregnancy. Dermatologic examination showed hemorrhagic bullae of the hands and feet. The left hand showed a hypoplastic index finger and absent nail from the thumb and index finger. The right hand revealed a hypoplastic third finger and nail (Fig. 1A). Both feet revealed band-like scarring at the ankle with bullae of the skin (Fig. 1B). Cutaneous macular erythema of the posterior neck and scattered red macules of the thighs, torso, and face were also noted.
Figure 1. First Week of Life. (A) Hands Showing Hemorrhagic Bullae. (B) Left Foot Showing Hemorrhagic Bullae and Ulceration.
Eye examination revealed bilateral nasal and temporal symblephara with forniceal foreshortening (Fig. 2, top). Friable corneal epithelium and inferior limbal pannus were noted bilaterally. Iris detail was clearly visualized and the retinae were normal. Work-up for sepsis revealed positive IgM and positive culture for cytomegalovirus. Genetics consultation showed normal 46 XX karyotype and noted microcephaly. Brainstem evoked response revealed complete bilateral sensorineural hearing loss.
Figure 2. (A) Right and (B) Left Corneas at 1 Week of Life Showing Nasal Symblephara and Visible Iris Detail. (C) Right and (D) Left Corneas at 15 Months Showing Dry Symblephara and Opacification.
Progressive corneal opacification occurred in both eyes. Lubricants and topical steroids were applied. At 8 weeks of age, a penetrating keratoplasty, lysis of symblephara, and superficial keratectomy of the right eye were performed. The corneal button pathology revealed opacified cornea, without inflammation. The left eye underwent superficial keratectomy followed by a penetrating keratoplasty at 12 weeks. Retinoscopy reflex was good in the right eye. The left corneal button showed opacified cornea with minimal focal peripheral mononuclear inflammatory cells. Vision was fix and follow to a lit toy with nystagmus.
At 5 months of age, a conjunctival membrane from the right eye showed conjunctival scarring, squamous metaplasia, fibrosis, and no goblet cell. At 6 months of age, an amniotic membrane graft applied to the left cornea was complicated by descemetocele with perforation necessitating an urgent patch graft. The right cornea became progressively more opacified with the visual axis obscured.
The right eye had four additional surgeries using azathioprine and topical cyclosporine: HLA-matched limbal stem cell transplant with amniotic membrane graft, penetrating keratoplasty with peripheral anterior synechiolysis, conjunctival flap to cover corneal ulcer, and resection of conjunctival tissue with repeat penetrating keratoplasty.
At 15 months of age, she could blink to light. The right cornea had reopacified except for a 2-mm central relatively clearer zone. Dry symblephara were noted in both eyes (Fig. 2, bottom). A B-scan ultrasound was normal in both eyes.
In contrast to the eyes, the dermatologic manifestations had improved by 1 month of age. The prior erosions reepithelialized without any recurrent blistering. Other prior erythematous macules had reduced to pinpoint size on the forehead and cheeks. The patient was given the clinical diagnosis of focal dermal hypoplasia in dermatologic consultation.
Early biopsies of the skin revealed only skin ulceration. Pathology of the left cornea showed extensive scarring at the time of penetrating keratoplasty that progressed in the corneal button within 2 months to total opacification and more fibrosis. At 16 months of age, a skin biopsy of a healed lesion on the right foot was performed. Electron microscopic study showed normal anchoring fibrils with good numbers and normal distribution.
The clinical presentation of this case yields the diagnosis of focal dermal hypoplasia, which is also called aplasia cutis congenital or Gorlin–Goltz syndrome.1 At term birth, the skin of the extremities was hypoplastic with absent epithelium. The skin lesions healed by 2 months of age without recurrent blistering. No mucous membrane involvement occurred.
Other diagnoses with early eye and skin disease were considered but ruled out by the clinical course or specialized testing. Epidermolysis bullosa was considered early on, but pathologic study ruled out the dystrophica type, which is most commonly associated with corneal pannus and scarring.2 Acquired syndactyly, as was noted in our case on the right hand and left foot, can be consistent with epidermolysis bullosa. However, the cutaneous blistering manifestations have never recurred in this child. Incontinentia pigmenti, which manifests as blisters anywhere on the body at or soon after birth, was ruled out when eosinophilia was not seen on early skin biopsy.3
Reviewing the online database Micromedix (Thomson Reuters), the medications given during pregnancy were unlikely to have been harmful. Nitrofurantoin is not classified as a human teratogen and cephalexin is not known to have any fetal risk. Promethazine is commonly used in labor for sedation and is generally considered safe for the mother and fetus. This mother received 25 mg of promethazine once for nausea.
Perinatal cytomegalovirus was a confounding factor with regard to the infant’s developmental delay and hearing loss. Microphthalmia with linear skin defects (MLS, formerly called MIDAS—microphthalmia, dermal aplasia, sclerocornea) is also a clinical consideration, but such lesions occur mostly on the face and neck and spare the extremities.1,4 Symblephara have never been described, although many cases have anomalies of external or internal genitalia. A reevaluation of the child’s karyotype at the 500 band level revealed no abnormality on the chromosome region of Xp22, to which both focal dermal hypoplasia and MLS have been mapped.5
As the skin lesions healed, the diagnosis of focal dermal hypoplasia was certain. Ophthalmic findings reported with focal dermal hypoplasia include anophthalmia, microphthalmia, coloboma, strabismus, lacrimal duct obstruction, opaque corneas, eyelid papillomas, and optic atrophy.6 Diffuse corneal opacities have been noted in focal dermal hypoplasia with microphthalmia and keratoconus.7 One report mentioned mild subepithelial corneal opacities in a mother and daughter.7 Symblephara have not been previously described in focal dermal hypoplasia. In our case, true symblephara were present at birth (Fig. 2). Cases of focal dermal hypoplasia have been reported with an initial inflammatory phase that subsides; in our case, the initial biopsy revealed neutrophil infiltration.8 A few cases have even been reported with typical skeletal and other deformities without the cutaneous manifestations.8 In our case, the hypoplastic digit and dysplastic nail at birth were consistent with focal dermal hypoplasia.
We are unaware of any prior report in the literature of congenital symblephara and corneal neovascularization progressing to full pannus in focal dermal hypoplasia.
- Goltz RW, Henderson RR, Hitch JM, Ott JE. Focal dermal hypoplasia syndrome: a review of the literature and report of two cases. Arch Dermatol. 1970;101:1–11. doi:10.1001/archderm.101.1.1 [CrossRef]
- Lin AE, Murphy F, Brodie SE, Carter DM. Review of ophthalmic findings in 204 patients with epidermolysis bullosa. Am J Ophthalmol. 1994;118:384–390.
- Landy SJ, Donnai D. Incontinentia pigmenti (Bloch-Sulzberger syndrome). J Med Genet. 1993;30:53–59. doi:10.1136/jmg.30.1.53 [CrossRef]
- Gunduz K, Gunalp I, Erden I. Focal dermal hypoplasia (Goltz’s syndrome). Ophthalmic Genet. 1997;18:143–149. doi:10.3109/13816819709057128 [CrossRef]
- Temple IK, MacDowall P, Baraitser M, Atherton DJ. Focal dermal hypoplasia (Goltz syndrome). J Med Genet. 1990;27:180–187. doi:10.1136/jmg.27.3.180 [CrossRef]
- Marcus DM, Shore JW, Albert DM. Anophthalmia in focal dermal hypoplasia syndrome. Arch Ophthalmol. 1990;108:96–100.
- Lueder GT, Steiner RD. Corneal abnormalities in a mother and daughter with focal dermal hypoplasia (Goltz-Gorlin syndrome). Am J Ophthalmol. 1995;120:256–258.
- Goltz RW. Focal dermal hypoplasia syndrome, an update. Arch Dermatol. 1992;128:1108–1111. doi:10.1001/archderm.128.8.1108 [CrossRef]