Oculoauriculofrontonasal Syndrome

Description

The OAFNS phenotype combines abnormalities of the morphogenesis of the first and second branchial arches (microtia/skin tags, epibulbar dermoids, cleft lip/palate, mandibular hypoplasia, and facial asymmetry) with malformations due to the anomalous development of the frontonasal eminence and maxillary processes (notched/bifid nasal tip, cleft lip and/or palate, and encephalocele) (Gabbett et al., 2008).

Clinical Features

Golabi et al. (1983) reported a brother and sister with an association of frontonasal dysplasia, ocular dermoids, and preauricular skin tags, who were born to a diabetic mother. Macrostomia and midbrain lipodermoid were found in the male. The authors proposed the designation oculoauriculofrontonasal dysplasia for this disorder. A girl with similar abnormalities was described by Musarella and Young (1986). Toriello et al. (1995) described a boy with this syndrome whose development at the age of 17 months was normal. Toriello et al. (1995) reviewed the features of frontonasal dysplasia (136760) and emphasized the importance of determining the type of eye defects and the form of the nose to distinguish OAFNS from frontofacionasal dysplasia (FFND; 229400).

Guion-Almeida and Lopes (1997) reported a Brazilian man, born to nonconsanguineous parents, who had midline craniofacial defects associated with branchial arch anomalies. The patient had macrocrania, an asymmetric face with primarily right-sided mandibular hypoplasia, hypertelorism, nose with broad root, right alar cleft, and bifid tip and columella, macrostomia, median lip notch, high palate, and right preauricular tags. X-ray of the spine was normal; brain CT showed lipoma of the falx and right periorbital lipomatosis. The patient, who was of normal intelligence, had 11 healthy sibs and 2 healthy children; another child died at 19 hours from respiratory problems but had no other anomalies. The authors reviewed the 14 published cases and noted the phenotypic overlap with FFND.

Ishmael et al. (2002) reported a 9-month-old male with oculoauriculofrontonasal syndrome. Features in their patient included bilateral cleft lip and palate, left preauricular skin tag, severely hypoplastic right pinna without an external canal, everted and hypoplastic left upper eyelid, notched broad nasal tip, ocular hypertelorism, micrognathia, hypoplastic mandible, extra cervical rib on the left, thoracic hemivertebrae, agenesis of the posterior corpus callosum with a midline lipoma, and an extra renal pelvis. Their review of the literature showed that many OAFNS features are variable, but all reported cases have had microtia/ear tags.

Gabbett et al. (2008) reported 4 additional cases of OAFNS and reviewed their features, together with those of 25 previously published cases. The authors suggested that OAFNS is statistically more likely to be a sporadically occurring condition than an inherited autosomal recessive trait, but stated that autosomal dominant transmission could not be excluded. Despite phenotypic overlap with oculoauriculovertebral spectrum (OAVS; 164210) and frontonasal dysplasia (FND; 136760), Gabbett et al. (2008) concluded that OAFNS has distinct features that distinguish it from those disorders. They noted that epibulbar dermoids and superior palpebral colobomata (which are not features of FND) occur significantly more frequently in OAFNS than in OAVS, and that OAFNS has fewer manifestations outside the craniofacial region (14%) compared with OAVS (50%).

Guion-Almeida and Richieri-Costa (2010) reported 2 unrelated Brazilian boys with high and narrow forehead, hypertelorism, downslanted palpebral fissures, broad nose, bilateral preauricular tags, alar clefts, dimple in the columella, cleft lip and palate, and pericallosal lipoma. Despite similarities with the oculoauriculofrontonasal syndrome, Guion-Almeida and Richieri-Costa (2010) suggested that these boys had a previously undescribed condition.