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Treacher Collins syndrome with novel ophthalmic findings and visceral anomalies
  1. J L Prenner1,
  2. G Binenbaum1,
  3. D F Carpentieri1,
  4. S M Goldstein1,
  5. R S Douglas1,
  6. E Ruchelli1,
  7. J A Katowitz1,
  8. R W Hertle2
  1. 1Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania; Departments of Pediatric Ophthalmology and Pathology, Children's Hospital of Philadelphia; Philadelphia, Pennsylvania, USA
  2. 2The Laboratory of Sensorimotor Research, The National Eye Institute, The National Institutes of Health; Bethesda, Maryland, USA
  1. Correspondence to: J L Prenner, MD, Department of Ophathalmology, Scheie Eye Institute, University of Pennsylvania, 51 North 39th Street, Philadelphia, PA 19106, USA; jlprenner{at}

Statistics from

Treacher Collins syndrome (TCS) (mandibulofacial dysostosis (MFD) or zygoauromandibular dysplasia) is one of a group of congenital malformation syndromes that have in common maldevelopment of the first and second branchial arches.1 Clinical features typically include hypoplasia of the mandible and zygoma; a complex variety of ear abnormalities including malformed pinnae, atresia of the external auditory canals and anomalies of the middle ear ossicles; cleft palate; receding chin; and sinus and choanal atresia.2 We present a pair of twins that possessed not only classic features of TCS but also unusual visceral and previously unreported ophthalmic pathology.

Case reports

A 32 year old, gravida 3 para 2-0-0-2 woman underwent elective abortion after fetal death and major fetal malformations were diagnosed during pregnancy. Ultrasound examination at 20 weeks of gestation displayed monozygotic, diamniotic twins. Fetus A, noted alive at 16 weeks, was dead and surrounded by minimal amniotic fluid. Fetus B was alive with several anomalies including bilateral infraorbital cystic masses, protruding tongue, and large median facial cleft. Amniocentesis revealed a 46XY karyotype without numerical or structural chromosomal abnormalities. The parents denied any significant medical history, family history, of congenital anomalies, or use of drugs or alcohol. Their two other children, ages 17 and 33 months, were normal. No family members exhibited features of TCS on visual examination.

Necropsy measurements were consistent with 16 weeks of gestational age for twin A and 21 weeks for twin B. Both twins had bilaterally hypoplastic zygomas, maxillae, and related muscles; severely hypoplastic and misplaced pinnae; bilaterally agenic external auditory canals; bilateral lateral facial clefts, and severe micognathia (Fig 1). Twin A exhibited left sided choanal atresia, agenesis of the hard and soft palate, and multiple visceral anomalies, including dual superior vena cava, bilobed right and unilobed left lungs, bilateral renal and ureteral agenesis, rudimentary urinary bladder, and absent epididymides. Twin B was noted to have right sided choanal atresia, soft palate aplasia, hard palate hypoplasia, and a left sided cleft; twin B had no visceral anomalies. Ocular pathological dissection of twin A illustrated bilateral microphthalmia; corneal scleralisation; and maldevelopment of the uvea, lens, and retina. Ocular dissection of twin B revealed microphthalmia, aniridia, congenital cataracts, and bilateral vascularisation of the corneas.

Figure 1

Gross photographs of fetal twins with features of Treacher Collins syndrome: (A) and (B) are twin B (21 weeks of gestational age); (C) is twin A (16 weeks of gestational age).


These twins had multiple features characteristic of TCS, most notably hypoplastic zygomas, maxillae, and related muscles—perhaps the most characteristic features of TCS. In contrast, visceral anomalies, such as those of twin A, are rare. Only two cases have been previously reported: one with tracheoesophageal fistula, rectovaginal fistula, and anal atresia; another with achalasia.3 Renal agenesis, found in twin A, has not been previously described in association with TCS. While ophthalmological features in TCS are often extensive, they seldom involve the intraocular structures. Common findings include a defective inferior lateral angle of the orbit, caudal displacement of the superolateral orbit, true and pseudocolobomas of the lids, lateral canthal dystopia, orbital lipodermoids, corneoscleral dermoids, and microphthalmos.4 Cataracts, lacrimal duct atresia, pupillary ectopia, distichiasis, and uveal colobomas have been reported less commonly. The extensive intraocular involvement in these twins is rare in TCS. Furthermore, aniridia, corneal scleralisation, and uveal, lens, and retinal maldevelopment are previously unreported.

TCS is an autosomal dominant disorder affecting one in 50 000 live births. The disorder appears to have arisen in these twins with no relevant family history, as occurs in 60% of cases.5 Expressivity is highly variable, ranging from clinically undetectable to perinatal death secondary to airway compromise6; the disease severity that resulted in the fetal death of twin A is highly unusual. The responsible gene, TCOF1, has been mapped to 5q32–33.2 7 and the structure of its protein product, treacle, elucidated.8 To date, 51 disease causing mutations have been identified,9 nearly all resulting in a premature termination codon.10 Significantly, no relation has been found between any single mutation and phenotype severity. The ophthalmic pathology observed in these twins may have resulted from a focal TCOF1 mutation and a yet to be defined role treacle may have in eye (and renal) development. Considering the number and severity of abnormalities, the failure to identify a single “genetic hot spot,” and the novel ophthalmic features, an alternative and perhaps more likely explanation is that a second gene, itself involved in ophthalmic embryology, was affected along with TCOF1. This unidentified gene may have been disrupted from a translocation involving 5q32–33.2 or from a deletion large enough to result in a contiguous gene syndrome. A final consideration is that these twins may not have had TCS but rather a new though closely related syndrome. Further genetic investigation may shed light upon these speculations.


JLP and GB contributed equally to this work.


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