Haldeman-Englert Chad R, Lin Angela E, Milunsky Jeff M
Cone Health, Greensboro, North Carolina
Genetics Unit, Massachusetts General Hospital for Children, Boston, Massachusetts
Branchiooculofacial syndrome (BOFS) is characterized by branchial (cervical or infra- or supra-auricular) skin defects that range from barely perceptible thin skin or hair patch to erythematous "hemangiomatous" lesions to large weeping erosions; ocular anomalies that can include microphthalmia, anophthalmia, coloboma, cataract, and nasolacrimal duct stenosis/atresia; and facial anomalies that can include dolichocephaly, hypertelorism or telecanthus, broad nasal tip, upslanted palpebral fissures, cleft lip or prominent philtral pillars that give the appearance of a repaired cleft lip (formerly called "pseudocleft lip") with or without cleft palate, upper lip pits, and lower facial weakness (asymmetric crying face or partial weakness of cranial nerve VII). Malformed and prominent pinnae and hearing loss from inner ear and/or petrous bone anomalies are common. Intellect is usually normal.
DIAGNOSIS/TESTING: The diagnosis of BOFS is established in a proband with characteristic clinical findings and a heterozygous pathogenic variant in identified by molecular genetic testing.
In general, children with BOFS should be managed by a multispecialty team including craniofacial specialists, plastic surgeons, otolaryngologists, and speech-language therapists. Small, linear, or superficial branchial skin defects may heal spontaneously; however, some require surgical intervention. Treatment of ophthalmic manifestations is per pediatric ophthalmologist. Nasolacrimal duct stenosis or atresia often requires surgery. Anophthalmia or severe microphthalmia may require a conformer (a structure, usually plastic, inserted into the eye socket to encourage its growth). It is recommended that cleft lip be repaired by an experienced pediatric plastic surgeon. Nasal tip abnormalities, lesser forms of cleft lip ("pseudocleft"), and malformed pinnae may need surgical correction. Standard treatments for hearing loss, renal malformations, dental manifestations, and congenital heart defects. Treatment of sensory, psychologic, and developmental challenges with supportive therapies. Ophthalmology examination and vision assessment as recommended by ophthalmologist; audiology evaluation as recommended by otolaryngologist and/or audiologist; at each visit assess for a recurrent urinary tract infection suggestive of vesicoureteral reflux, assess teeth for size, number, carries, and malocclusion, and assess for new cysts; developmental and behavioral assessment annually or as needed; monitor for signs of low self-esteem and other psychological issues at each visit in older children as they enter adolescence.
BOFS is inherited in an autosomal dominant manner. pathogenic variants are observed in 50%-60% of affected individuals. Each child of an individual with BOFS has a 50% chance of inheriting the pathogenic variant. Once the pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.
鳃耳颜面综合征（BOFS）的特征包括鳃部（颈部或耳前或耳上）皮肤缺损，范围从几乎难以察觉的薄皮肤或毛发斑块到红斑性“血管瘤样”病变，再到大面积渗液糜烂；眼部异常，可包括小眼症、无眼症、缺损、白内障以及鼻泪管狭窄/闭锁；面部异常，可包括长头畸形、眼距过宽或内眦距过宽、鼻尖宽大、睑裂向上倾斜、唇裂或明显的人中嵴，形似已修复的唇裂（以前称为“假性唇裂”），可伴有或不伴有腭裂、上唇凹陷以及面下部无力（不对称哭脸或面神经VII部分无力）。耳廓畸形突出以及内耳和/或岩骨异常导致的听力损失很常见。智力通常正常。
诊断/检测：BOFS的诊断基于先证者具有特征性临床发现以及分子遗传学检测确定的杂合致病变异。
一般而言，BOFS患儿应由多学科团队管理，包括颅面外科专家、整形外科医生、耳鼻喉科医生和言语治疗师。小的、线性的或浅表的鳃部皮肤缺损可能会自发愈合；然而，有些需要手术干预。眼科表现的治疗由儿科眼科医生进行。鼻泪管狭窄或闭锁通常需要手术。无眼症或严重小眼症可能需要佩戴眼模（一种通常为塑料的结构，插入眼窝以促进其生长）。建议由经验丰富的儿科整形外科医生修复唇裂。鼻尖异常、较轻形式的唇裂（“假性唇裂”）和耳廓畸形可能需要手术矫正。针对听力损失、肾脏畸形、牙齿表现和先天性心脏病缺陷的标准治疗方法。通过支持性疗法处理感觉、心理和发育方面的挑战。按照眼科医生的建议进行眼科检查和视力评估；按照耳鼻喉科医生和/或听力学家的建议进行听力评估；每次就诊时评估是否有提示膀胱输尿管反流的复发性尿路感染，评估牙齿的大小、数量、龋齿和错牙合情况，并评估是否有新囊肿；每年或根据需要进行发育和行为评估；在大龄儿童进入青春期时，每次就诊时监测是否有自卑迹象和其他心理问题。
BOFS以常染色体显性方式遗传。50%-60%的受影响个体存在致病变异。BOFS患者的每个孩子有50%的机会继承致病变异。一旦在受影响的家庭成员中确定了致病变异，就可以进行产前和植入前基因检测。
