ß 2008 Wiley-Liss, Inc. American Journal of Medical Genetics Part A 146A:2169–2171 (2008) Research Letter Genital Anomalies in a Patient With Treacher Collins Syndrome Karin Writzl, 1,2 * Jera Jeruc, 3 Michael Oldridge, 4 Borut Peterlin, 1 and Raoul C.M. Hennekam 2,5,6 1 Institute of Medical Genetics, UMC, Ljubljana, Slovenia 2 Department of Clinical Genetics, Great Ormond Street Hospital for Children, UCL, London, UK 3 Faculty of Medicine, Institute of Pathology, University of Ljubljana, Ljubljana, Slovenia 4 Molecular Genetics Laboratory, The Churchill Hospital, Oxford, UK 5 Clinical and Molecular Genetics Unit, Institute of Child Health, UCL, London, UK 6 Department of Paediatrics, AMC, Amsterdam, The Netherlands Received 12 April 2008; Accepted 7 May 2008 How to cite this article: Writzl K, Jeruc J, Oldridge M, Peterlin B, Hennekam RCM. 2008. Genital anomalies in a patient with Treacher Collins syndrome. Am J Med Genet Part A 146A:2169 –2171. To the Editor: Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development including symmetrical abnormalities of external ears and hearing, hypoplasia of mandible and of the zygomata with downward slant of palpebral fissures [Gorlin et al., 2001]. Diagnosis may be difficult due to extreme variability in expression. Non-craniofacial anomalies are rare but a patient with tracheoeso- phageal fistula, anal atresia and rectovaginal fistula has been described [Robb et al., 1991]. Here, we report on one patient with extreme facial involve- ment of TCS and severe genital anomalies. The patient was the first child of healthy, non- consanguineous parents. Family history was un- remarkable, and pregnancy was uncomplicated. He was born spontaneously at 39 6 / 7 weeks of gestation. Birth weight was 2,750 g (10th centile), length was 48 cm (10th–25th centile), and head circumference 33.5 cm (10th–25th centile). He died shortly after birth. Multiple facial anomalies were present: high and broad forehead, hypoplastic supraorbital ridges, scarce eyebrows, downwardly slanted, asymmetri- cally positioned palpebral fissures, and absence of eyelashes on the outer third of the right lower lid (Fig. 1). No globes were recognized at first, but on autopsy small globes were present (10 mm in anteroposterior diameter, normal value in infants 17.5 mm) [Garner, 1998] (Fig. 2). He had severe nasal hypoplasia with bilateral choanal atresia, extremely hypoplastic zygomatic bones, and bilateral trans- verse facial clefts extending from the oral commis- sures, crossing the cheeks, and ending at the site where ears would normally be present (left) or about 1 cm anterior to that site (right). There were rudimentary ears (microtia grade III) with absent auditory meatus. Tongue-shaped processes of hair extended from the temporal area toward the facial clefts. The neck was short, and excluding genitalia, trunk and limbs were normal. External genitalia: microphallus (4 mm) and small scrotum (Fig. 3) without hypospadias. Internal examination showed a urogenital sinus into which a vagina and urethra ended. The rectum drained through a normally placed anus. There was a small bicornuate uterus with Fallopian tubes (Fig. 4). Intra- abdominally there were two gonads (left 15 mm and right 17 mm in diameter, respectively) which on histologic study proved to be testes with para- testicular structures (Fig. 5). Chromosomes were normal (46,XY). The findings were consistent with ‘‘male pseudohermaphroditism’’ (46,XY, disorder of sex development). The clinical diagnosis of TCS was confirmed by molecular analysis showing a heterozygous one base pair deletion of a G nucleotide at position 4,321 of the TCOF1 gene (exon 23), causing a frame shift at glutamate 1,441 (p.E1441fs). The normal other allele excluded hemizygosity or uniparental isodisomy causing homozygosity for a TCOF1 mutation. The mutation was not detected in either parent. To our knowledge, similar genital anomalies have not been described previously in TCS. One girl was *Correspondence to: Dr. Karin Writzl, Institute of Medical Genetics, UMC, S ˇ lajmerjeva 3, 1000 Ljubljana, Slovenia. E-mail: karinwritzl@gmail.com DOI 10.1002/ajmg.a.32404