The oculo-auriculo-fronto-nasal syndrome (OAFNS) – Description of a rare and complex craniofacial deformity and its interdisciplinary management before school age

Oculoauriculofrontonasal syndrome: Case series revealing new bony nasal anomalies in an old syndrome

“…Recently, cilia have received much attention because of the new appreciation for their role in transmitting morphogenetic and growth promoting signals to cells. Consistent with this notion, recent data suggested that genes encoding ciliary proteins present on neural crest cells may be one cause of abnormal frontonasal development [Brugmann et al, ; Adolphs et al, ]. However, the anomalies involving the eyelid and cornea likely result from a defect in epithelial derived tissues.…”

“…However, encephaloceles are present in only seven children with OAFNS [Tillman, ; Gupta et al, ; Tarateta et al, ; Gustavson and Chen, ; Kennedy et al, ; Gabbett et al, ]. Midline intracranial lipomas are common in OAFNS [Golabi et al, ; Musarella and Young, ; Naidich et al, ; Guion‐Almeida and Lopes, ; Ishmael et al, ; Gabbett et al, ; Guion‐Almeida and Richieri‐Costa, ; Adolphs et al, ]. While cognitive abnormalities are not well‐described in OAFNS, developmental delay or learning problems are present in approximately a third of patients with OAFNS [Tillman, ; Cohen et al, ; Musarella and Young, ; Naidich et al, ; Gabbett et al, ; Guion‐Almeida and Richieri‐Costa, ].…”

“…Gupta et al [] reported a 4‐month‐old male with epibulbar dermoids, preauricular tags, microtia, hypertelorism, a broad cleft nose, a frontal meningo‐encephalocele with an associated skull defect, and hydrocephalus and called this severe form of Goldenhar syndrome “Oculo‐auricular cranial dysplasia.” Since the 1960s, 32 individuals with similar overlapping features of OAVS and FND have been described in the literature, with clinical diagnoses including bilateral Goldenhar anomaly, ophthalmofrontonasal dysplasia, Type III (frontonasal type) hemifacial microsomia, and Golabi–Gonzalez–Edwards syndrome [Tillman, ; Gupta et al, ; Fleischer‐Peters, ; Cohen, ; Tarateta et al, ; Carey, ; Castillo et al, ; Fontaine et al, ; Golabi et al, ; Gustavson and Chen, ; Musarella and Young, ; Naidich et al, ; Toriello et al, ; al‐Gazali et al, ; Casey et al, ; Guion‐Almeida and Lopes, ; Kennedy et al, ; Ishmael et al, ; Johnson et al, ; Guion‐Almeida and Richieri‐Costa, ; Roman Corona‐Rivera et al, ; Gabbett et al, ; Adolphs et al, ]. In 1981, Carey and Yong termed this condition “Oculoauriculofrontonasal syndrome” [Carey, ].…”

The oculoauriculofrontonasal syndrome: Further clinical characterization and additional evidence suggesting a nontraditional mode of inheritance

“…All cytogenetic and molecular investigations reported in patients with OAFNS in the literature were negative, including karyotype, array comparative genomic hybridization (CGH) (Adolphs et al, ; Guimiot et al, ; Tunc et al, ), ALX3 (Adolphs et al, ) and GLI3 (Guimiot et al, ) sequencing. We performed trio‐based ES and GS in three patients and their healthy parents, looking in the first step for de novo variants, as the occurrence of OAFNS is usually sporadic.…”

“…The craniofacial tissues derive from the cranial neural crest cells, a population of pluripotent cells that arise from the dorsal aspect of the neural tube and migrate to populate the frontonasal process and the first, second, third, and fourth pharyngeal arches (Le Lievre & Le Douarin, ). About 40 individuals with OAFNS have been described in the literature (Adolphs et al, ; Casey, Braddock, Haskins, Carey, & Morales, ; Evans et al, ; Gabbett et al, ; Gawrych, Janiszewska‐Olszowska, & Chojnacka, ; Golabi, Gonzalez, & Edwards, ; Gupta et al, ; Ishmael, Begleiter, Regier, & Butler, ; Johnson, Benoit, Pierre‐Louis, Keating, & Chitayat, ; Musarella & Young, ; Roman Corona‐Rivera et al, ; Toriello, Higgins, & Mann, ; Tunc et al, ). Except for two siblings born from a diabetic mother (Golabi et al, ), all have a sporadic occurrence.…”