Otofaciocervical syndrome: a sporadic patient supports splitting from the branchio-oto-renal syndrome.

A sporadic patient with OFC syndrome is described. Distinguishing features were a long face with narrow nose, high arched palate, prominent and dysmorphic ears, long neck, sloping shoulders and clavicles, winged, low, and laterally set scapulae, tetralogy ofFallot, and deafness secondary to cochlear malformation. Some features present in the original family, including lateral cervical fistulae, have suggested that OFC syndrome could be a variant of BOR syndrome. The absence of preauricular tags, lacrimal duct stenosis, and renal malformations, and the presence of distinct facial and radiographic findings and markedly downward sloping shoulders in the present patient support OFC syndrome being a unique, clinically recognisable entity. (JMed Genet 1995;32:816-818) Department of Public Health and Cell Biology, Tor Vergata University of Rome, and CSS Hospital, San Giovanni Rotondo, Italy B Dallapiccola R Mingarelli Correspondence to: Dr Dallapiccola, Department of Public Health and Cell Biology, Tor Vergata University, Via di Tor Vergata 135, I-00133 Roma, Italy. Received 2 February 1995 Revised version accepted for publication 22 June 1995 Otofaciocervical syndrome (OFS) was originally described by Fara et al' in a man and in four of his seven children. Distinguishing features were short stature, long face with a relatively broad forehead and narrow mandible and nose, sunken nasal roots, high arched palate, prominent ears with large conchae, preauricular fistulas, lateral cervical fistulas in some patients, long neck with downward sloping shoulders and clavicles, laterally displaced with winged scapulae, bilateral conductive hearing loss, and mild intellectual deficit. Although the combination of characteristic face, auricular abnormalities, hearing loss, and sloping shoulders is unique, the possibility has been discussed that OFCS is a variant of the branchio-oto-renal (BOR) syndrome.2 This suggestion was supported by a boy who had overlapping features of OFCS and BOR syndrome, including inability to raise the left arm, long neck, and sloping shoulders,3 and by a patient with lacrimal duct stenosis, preauricular fistula and tag, sloping shoulders, normal genitourinary system, and spina bifida occulta.4 We report a sporadic patient with the features of OFCS in whom the absence of most of the distinguishing characteristics of BOR syndrome supports the syndrome originally described by Fara et al' being a distinct, clinically recognisable entity. Case report The proband, a girl, the second child of nonconsanguineous, phenotypically normal parents, was born in the 37th week of gestation, after an uneventful pregnancy. An older sister is healthy. Birth weight was 2800 g (25th centile), length 47 cm (25th centile), and head circumference 33 cm (25th centile). The neonatal period was characterised by respiratory distress and cyanosis. Tetralogy ofFallot was diagnosed at 1 month of age, and surgically repaired at the ages of 5 and 7 years. Bilateral sensorineural deafness was diagnosed at 1 year. This girl was first referred to us at the age of 13 years 2 months (fig 1). Heightwas 152 cm (between the 25th and 50th centile), weight 42 kg (between the 25th and 50th centile), and head circumference 52 cm (<50th centile). Clinical examination showed an elongated face with an inverted triangular shape, broad forehead, pinched nose, mildly upward slanted palpebral fissures, open lacrimal ducts, inturning upper lip, high arched palate, and malocclusion. The ears were prominent, slanted, and grossly dysmorphic, with large conchae and hypoplastic tragus, antitragus, and lobe, in the absence ofpreauricular fistulas and tags (fig 2). The neck appeared long, without branchial cleft, sinus, or cysts, but with posteriorly prominent cervical vertebrae. Shoulders and clavicles were markedly downward sloping and the scapulae winged and more laterally located than normal. Kyphosis and marked lumbar lordosis were also present. The fingers were thin and long and the hallux valgus bilaterally. Neurological evaluation and intellectual development were grossly normal. An ultrasound examination ofthe abdominal organs disclosed morphologically normal and well positioned kidneys and normal liver, uterus, and ovaries. IVP was also normal. A systematic x ray skeletal survey showed a turricephalic skull, narrowing of the middle third of the face, a deep sella turcica, steep clivus, hyperpneumatised paranasal sinuses, and poor mastoid pneumatisation. A flattened glenoid cavity was found at the temporomandibular articulation. The shoulders were low. The straight and obliquely downward slanted clavicles were at the level of the fourth rib (fig 3). The scapulae were low and laterally set, with an anterior opening of the glenoid cavities. The spine showed a reduced AP diameter of C1 to C4, a trapezoidal shape of 816 Otofaciocervical syndrome: a sporadic patient supports splitting from the branchio-oto-renal syndrome Figure 3 Radiograph showing depressed position of shoulders, clavicles at the level of the fourth rib, with outer ends running obliquely downwards. Figure 1 Four views of the OFCS patient showing characteristic facies with abnormal ears and sloping shoulders. Figure 2 Right ear ofproband. C6 to DI bodies, an enlarged vertebral canal, and mildly dysmorphic lumbar vertebrae. Acetabular angles were narrow with valgus hips, overtubulated long bones, and dysmorphic trapezium. Bone age was normal. A CT scan of the inner ear disclosed bilaterally bipartite cochlea, absent lateral semicircular canals, and dilated vestibulum (fig 4). Chromosomes were normal both on standard and high resolution analysis, including scrutiny of 8q. The association between facial abnormalities, oto-cervical defects, and tetralogy of Fallot prompted a search for microdeletion within the 22qll region. Molecular analysis was carried out on genomic DNA obtained from leucocytes using probe HD7k and on metaphase spreads using fluorescent in situ hybridisation (FISH) with probe Scd 1.1, basically according to Amati et al.5 No evidence of deficiency of region 22ql 1 was obtained in this patient. Discussion The family with abnormalities of the external ear, face, and neck originally described by Fara Figure 4 CT scan of inner ear showing bipartite cochlea, absent lateral semicircular canal, and dilated vestibulum. 817