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

Abstract

The oculoauriculofrontonasal syndrome (OAFNS) is a rare disorder characterized by the association of frontonasal dysplasia (widely spaced eyes, facial cleft, and nose abnormalities) and oculo-auriculo-vertebral spectrum (OAVS)-associated features, such as preauricular ear tags, ear dysplasia, mandibular asymmetry, epibulbar dermoids, eyelid coloboma, and costovertebral anomalies. The etiology is unknown so far. This work aimed to identify molecular bases for the OAFNS. Among a cohort of 130 patients with frontonasal dysplasia, accurate phenotyping identified 18 individuals with OAFNS. We describe their clinical spectrum, including the report of new features (micro/anophtalmia, cataract, thyroid agenesis, polymicrogyria, olfactory bulb hypoplasia, and mandibular cleft), and emphasize the high frequency of nasal polyps in OAFNS (56%). We report the negative results of ALX1, ALX3, and ALX4 genes sequencing and nextgeneration sequencing strategy performed on blood-derived DNA from respectively, four and four individuals. Exome sequencing was performed in four individuals, genome sequencing in one patient with negative exome sequencing result. Based on the data from this series and the literature, diverse hypotheses can be raised regarding the etiology of OAFNS: mosaic mutation, epigenetic anomaly, oligogenism, or nongenetic cause. In conclusion, this series represents further clinical delineation work of the rare OAFNS, and paves the way toward the identification of the causing mechanism.

Toward clinical and molecular dissection of frontonasal dysplasia with facial skin polyps: From Pai syndrome to differential diagnosis through a series of 27 patients

“…Patients 1, 3, 4, 6, and 2, 5, and 11 have been previously reported in Morice et al (2019), Chousta et al (2008), de Boutray et al (2016), and Lederer et al (2012). Patients 21 and 22 have been reported by our group in Lehalle et al (2018). Four were fetuses from termination of pregnancy or death in utero.…”

Síndrome oculoauriculofrontonasal: caracterização fenotípica

“…Uma dessas síndromes é a síndrome oculoauriculofrontonasal (OAFN; OMIM 601452), também chamada de síndrome de Golabi-Gonzales-Edwards e displasia oftalmofrontonasal, que representa a associação dos achados clínicos de duas condições: o espectro oculoauriculovertebral (EOAV; OMIM 164210) e a displasia frontonasal (DFN; OMIM 136760) (CASEY et al, 1996;GORLIN, COHEN JR, HENNEKAM, 2001;GABBETT et al, 2008;LEHALLE et al, 2018).…”

“…Os autores sugeriram a classificação da síndrome OAFN como uma entidade distinta da displasia frontonasal (DFN; OMIM 136760) e do espectro oculoauriculovertebral (EOAV; OMIM 164210). A classificação da síndrome OAFN como uma síndrome distinta é apoiada por diversos estudos (GABBETT et al, 2008;EVANS et al, 2013;LEHALLE et al, 2018).…”

“…A respeito da etiologia desse osso, uma hipótese é que ele seja resultante da ossificação anormal das cartilagens do nariz, (EVANS et al, 2013). No entanto, a etiologia do osso nasal ectópico ainda permanece desconhecida (LEHALLE et al, 2018).…”

“…O critério proposto por Guion-Almeida (2000) considera que os achados clínicos obrigatórios para o diagnóstico incluem hipertelorismo ocular, base nasal larga, apêndices pré-auriculares e assimetria facial. O critério mais recentemente publicado, e que inclui o osso nasal ectópico, foi proposto por Lehalle et al (2018) (Quadro 1). Nesse critério, hipertelorismo ocular, apêndices pré-auriculares e/ou anomalias auriculares e assimetria facial são achados obrigatórios para o diagnóstico, semelhante ao critério proposto anteriormente por Guion-Almeida (2000).…”