Further delineation of the branchio‐oculo‐facial syndrome

Abstract

We review 43 p atie n ts (15 new, 28 literature) w ith the branchio-oculo-facial (BOF) syn drome, w h ic h has a d istin ctiv e phenotype ran g in g from m ild to severe forms, consist in g of eye, ear, oral, a n d craniofacial anom alies. V irtu a lly u b iq u ito u s and possibly pathognom onic are the cervical/infra-auricu la r sk in defects. M uch less common are supra-auricular defects occurring as iso late d anom alies or w ith cervical defects. Re gardless of lo catio n , these lesions may have aplastic, "hem angiom atous," or otherwise abnorm al overlying skin, and d ra in in g sinus fìstulae. R e n a l m alfo rm atio ns are frequent, b u t congenital h e a rt a n d central nervous system defects are rare* Psychomotor per form ance is u s u a lly norm al, b u t develop m ent delays, h y p o to n ia , and visual, hearing, and speech problem s are common. Autoso m al d o m in a n t in h e rita n c e seems likely. Overlap betw een the B O F and branchio-otorenal syndromes has been observed, b u t elu cidation o f its m o le cu lar basis is not yet available. This article also discusses 5 p a tients w ith aty p ical m anifestations consid ered to be possibly affected or probably u n affected, w ho are sufficiently unusual to be excluded from the fin a l data analysis.

Síndrome brânquio-óculo-facial (BOFS) e cardiopatias congênitas

“…The presence of some specific craniofacial anomalies in our patient, particularly telecanthus, broadened nasal bridge, lip pseudocleft, dysplastic and posteriorly-rotated ears associated with branchial clefts, which are considered possibly pathognomonic of BOFS 3 , supported the diagnosis. In medical databases such as OMIM 1 and LMD (London Medical Database) 6 , there is no description of the association between BOFS and congenital heart defects.…”

“…In medical databases such as OMIM 1 and LMD (London Medical Database) 6 , there is no description of the association between BOFS and congenital heart defects. However, in our review, we found four confirmed cases of BOFS presenting CHD which included: ostium secundum atrial septal defect (two cases) 3,7 , tetralogy of Fallot (one case) 5 and pulmonary valve stenosis (one case) 8 (Table 1). All patients presented facial findings characteristic of BOFS associated with branchial defects 1,3,5,8 .…”

“…Branchio-oculo-facial syndrome (BOFS) (MIM 113620) 1 , first named in 1987 by Fujimoto et al 2 , is a rare autosomal disease with a highly variable expressivity 3 . Mutations in genes of the EYA-DACH-SIX-PAX pathway, initially considered candidates for the syndrome because of their relationship with the development of some oro-facial-cervical structures and diseases overlapping with BOFS, such as the branchiooto-renal syndrome (BOR; MIM 113650) and Townes-Brocks syndrome (TB; MIM 107480), have not been identified in BOFS patients.…”

“…Despite these findings, the authors concluded that more patients should be studied to exclude possible genetic heterogeneity 4 . The syndrome is clinically characterized by the presence of branchial defects covered by a portion of normal skin, associated or not with pre-auricular or auricular pits; microphtalmia; coloboma; nasolacrimal duct obstruction; lip pseudoclefts (abnormal upper lip and filtrum resembling a poorly repaired cleft lip); partial or total clefts of upper lip, and premature graying of hair 2,3 .…”

“…Although renal malformations are frequent in patients with the syndrome, the involvement of other organs, particularly congenital heart defects (CHD) have been rarely described 3,5 . We report a rare case of BOFS associated with CHD.…”