In 1963, Setleis and colleagues reported on five patients with characteristic facial features and a common birthplace.1 Subsequently, six other patients have been reported in the literature.2"5 Setleis syndrome is characterized by leonine facies with redundant periorbital skin, wide nasal bridge, "parrot beak" nose, and thickened lips; bitemporal focal oval lesions resembling forceps scars, hence the alternate term of forceps marks syndrome; sparseness or absence of the temporal third of the eyebrows; multiple rows of lashes on the upper lids; sparse or absent lashes on the inferior lids.
These findings represent abnormalities of the facial skin and its appendages, qualifying it as an ectoderma! dysplasia syndrome.
Setleis syndrome follows an autosomal recessive pattern of inheritance.3 The families of 8 of the 11 patients reported were traced to northwestern Puerto Rico, specifically the San Sebastián-Aguadilla area.1-3
We present the first report of congenital absence of meibomian glands in Setleis syndrome. The congenital absence of meibomian glands is an exceedingly rare finding and has been reported only in association with the ectrodactyly, ectoderma! dysplasia, cleft lip-palate (EEC) syndrome6 and hypohidrotic ectoderma! dysplasia,7 which are other ectodermal dysplasia syndromes.
In October 1987, two Puerto Rican sisters were referred to the Yale Eye Center by their pediatrician for evaluation of photophobia. One was 10 years old, the 2.98 kg product of a full-term gestation of an 18-year-old primagravida. The pregnancy was complicated by maternal mumps during the seventh month. She was born by normal, spontaneous, nonforceps vaginal delivery. The other was 9 years old, the 2.55 kg product of a full- term gestation of the same parents. The pregnancy was uncomplicated and resulted in a normal, spontaneous, nonforceps vaginal delivery.
At birth, they were both noted to have red marks bitemporally and unusual facial features. Neither had neonatal complications. Their development was normal, and they are good students. They have had no major illnesses, surgery, trauma, or allergic reactions. They resemble no other members of their family. Family history was noneontributory for congenital malformations or hereditary diseases. Both parents hail from northwestern Puerto Rico and are from presumedly unrelated families.
Their corrected visual acuities were OD: counting fingers at three feet, OS: 20/60; and OD: 20/70, OS: 20/70, respectively. Cycloplegic refractions were OD: -19.50 +4.50 ? 090, OS: -10.50 +5.00 ? 090; and OD: -7.50 +6.00 ? 090, OS: -9.00 +8.00 ? 090, respectively.
Keratometry readings were OD: 44.50 ? 015, 48.00 ? 105, OS: 42.75 ? 180, 50.00 ? 090; and OD: 44.50 ? 175, 51.00 ? 085, OS: 44.50 ? 170, 51.50 ? 080, respectively.
External examinations were significant for bitemporal patches of erythematous, scarred skin measuring approximately 2 ? 2.5 cm. They had redundant facial and periorbital skin and thickened lips. The lateral aspect of the eyebrows were absent bilaterally (Fig 1). Neither had cilia in the lower lids, and in the upper lids, they had a decreased number of coarse cilia arranged in multiple horizontal rows (Fig 2).
They had full motility and were orthotopic at distance and near on cover testing. The older sister had no stereopsis on Titmus testing, while the younger had normal stereopsis.
Slit-lamp examinations revealed bilaterally thin tarsi. Meibomian gland orifices were absent in superior and inferior lids bilaterally (Fig 2). Fluorescein staining of their corneas revealed mild, diffuse punctate epithelial staining bilaterally. Anterior segments were otherwise quiet and unremarkable.
Fig 1 (Top) Facial features ofSetleis syndrome in reported siblings: 1) Absent lateral portion of eyebrows, 2) bitemporal scarred, erythematotis skin resembling forceps scars, 3) redundant facial and periorbital skin, 4) "parrot-beak" nose, and 5) thickened lips. (Bottom) Higher magnification of temporal aspect showing scarred, erythematous skin resembling forceps scar.
Five-minute unanesthetized Schinner testing results were OD: 30 mm, OS: 29 mm, and OD: 20 mm, OS: 26 mm, respectively, which were within normal limits. Tear breakup times (BUT) were instantaneous bilaterally in both patients. Funduscopic examinations were unremarkable.
The diagnosis of Setleis syndrome was made on the basis of autosomal recessive inheritance and physical findings. Tear instability was attributed to congenital absence of the meibomian glands. They also had high myopia and astigmatism, with the older also having anisometropic amblyopia.
Visual acuities were reduced largely on the basis of corneal changes, except in the right eye of the older sister with anisometropic amblyopia. Aggressive lubrication with artificial tears resulted in resolution of the punctate keratopathy with concomitant improvement in visual acuity to OD: counting fingers at 5 feet; OS: 20/30; and OD: 20/30; OS: 20/30.
The family was referred to the Department of Genetics for evaluation and counseling. Their workup revealed no gross chromosomal abnormalities.
Fig 2: View of lids showing decreased number of cilia in multiple rows in upper lid, and essentially absent complement of cilia in lower lid. Also note absence of meibomian gland orifices in everted upper lid.
We report the congenital absence of meibomian glands in Setleis syndrome, a rare autosomal recessive facial ectodermal dysplasia syndrome affecting almost exclusively patients of Puerto Rican descent. The inheritance pattern differentiates this syndrome from the other form of facial ectodermal dysplasia, which is the focal facial dermal dysplasia (FFDD) syndrome. FFDD syndrome is divided into an autosomal dominant Brauer syndrome and a sporadic Jensen syndrome.8 There seems to be a wide spectrum of facial findings in FFDD syndrome,9 in contrast to the characteristic facies of Setleis syndrome.
The patients herein described lacked meibomian gland orifices. Although lid biopsy would have provided definitive histopathologic evidence, diagnostic biopsy was deferred. The physiologic findings in these patients, however, support the diagnosis: normal results on Schirmer tests, suggesting an intact aqueous component of the tears; and instantaneous tear break-up times, demonstrating the instability of the tear film due to absence of the superficial lipid layer.
The meibomian glands are racemose holocrine glands located within the tarsi. The orifices are located at the lid margins, anterior to the mucocutaneous junction. The openings are arranged in a linear pattern and are surrounded by well-vascularized epithelial tissue. The secretions from these glands form the superficial lipid layer of the tear film, which is thought to retard evaporation. Thus, in the absence of meibomian lipid, one would expect normal production of the aqueous component of the tear film, accompanied by its hastened evaporation. Such a nonwetting problem explains the diffuse breakdown of corneal epithelium despite normal Schirmer tests. Interestingly, young patients with lipid tear deficiency usually do not present until after the first decade of life, as described by Bron and colleagues.10 These investigators attribute the delayed presentation to a more resilient ocular surface in children. Another interesting finding relates to the tarsal plates. The concurrent finding of hypoplastic tarsal plates is a rare anomaly that has been associated with absence or hypoplasia of meibomian glands.10
It is noteworthy that congenital absence of meibomian glands has only been reported in association with other ectoderma! dysplasia syndromes, namely the EEC syndrome6 and the hypohidrotic ectodermal dysplasia syndrome.7 These syndromes are characterized by systemic abnormalities or deficiencies in accessory skin structures such as hair, teeth, and glands. The reproducibility of the pattern of defects, such as the lobster-claw hands and feet as well as the facial findings in EEC syndrome, point to disruption of migratory or cell-differentiation cues as the etiology. The meibomian glands, therefore, represent but one of these affected epithelial appendages. Thus, these patients may have one or more components of the ocular surface affected, and all components must be evaluated for appropriate diagnosis and management.
1. Setleis H, Kramer B, Valcárcel M1 Einhorn AH. Congenital ectodermal dysplasia of the face. Pediatrics. 1963;32:540-547.
2. Rudolph RI1 Schwartz W, Leyden JJ. Bitemporal aplasia cutis congenita: occurrence with other cutaneous abnormalities. Arch Dermatol. 1974a;110:615-618.
3. Marion RW, Chitayat D, Hutcheon G, Goldberg R, Shprintzen RJ, Cohen MM. Autosomal recessive inheritance in the Setleis Bitemporal "Forceps Marks" Syndrome. The American Journal of Diseases in Children. 1987;141:895-897.
4. Clark RD, Golabi M, Lacassie Y, HaU B, Seto S. Expanded phenotype and ethnicity in Setleis syndrome. Am J Med Genet. 1989;34:354-357.
5. Frederick DR, Robb RM. Ophthalmic manifestations of Setleis forceps marks syndrome. J Pediatr Ophthalmol Strabismus. 1992;29:127-129.
6. Mondino BJ, Bath PE, FOOB RY, Apt L, Rajacich GM. Absent meibomian ghinda in the ectrodactyly, ectodermal dysplasia, cleft lip-palate syndrome. Am J Ophthalmol. 1984;97: 496-500.
7. Ekins MBC, Waring GO. Absent meibomian glande and reduced corneal sensation in hypohidrotic ectodermal dysplasia. J Pediatr Ophthalmol Strabismus. 1981; 18:44-51.
8. Freire-Maia N1 Pinheiro M. Ectodermal Dysplasias: A Clinical and Genetic Study. New York, NY: Alan Liss; 1984:165-167.
9. Di Lernia V, Neri I, Patrizi A. Focal facial dermal dysplasia: two familial cases. JAm Acad Dermatol. 199 1;25: 389-391.
10. Bron AJ, Mengher LS. Congenital deficiency of meibomian glands. Br J Ophthalmol. 1987;7 1:312-314