Lüdecke Hermann-Josef, Wieczorek Dagmar
Institut für Humangenetik Universitätsklinikum Düsseldorf Heinrich-Heine-Universität Düsseldorf, Germany
-related craniofacial disorders comprise a range of phenotypes that includes: isolated choanal atresia; choanal atresia with minor anomalies; and Burn-McKeown syndrome (BMKS), which is characterized by typical craniofacial features (bilateral choanal atresia/stenosis, short palpebral fissures, coloboma of the lower eyelids, prominent nasal bridge with widely spaced eyes, short philtrum, thin vermilion of the upper lip, and prominent ears). Hearing loss is common and cardiac defects and short stature have been reported. Intellectual disability is rare.
DIAGNOSIS/TESTING: The diagnosis of a -related craniofacial disorder is established in a proband with suggestive findings and biallelic pathogenic variants in identified by molecular genetic testing. All probands described to date have had at least one copy of one of the two partially overlapping 34-bp deletions in the promoter.
Neonates with airway compromise at delivery may require intubation or surgical correction of choanal stenosis/atresia. Defects of the lower eyelids that can result in corneal exposure require care by an ophthalmologist to reduce the risk of corneal scarring. Treatment of hearing loss is individualized and may involve hearing aids. Treatment of craniofacial manifestations (e.g., cleft lip and/or palate, preauricular tags, prominent ears) is individualized and managed by a multidisciplinary team. Cardiac defects are managed in a routine manner. Monitoring by an ophthalmologist, audiologist, and craniofacial team is recommended.
-related craniofacial disorders are inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance inheriting neither of the familial pathogenic variants. Once the pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.
-相关的颅面疾病包括一系列表型，其中有：孤立性后鼻孔闭锁；伴有轻微异常的后鼻孔闭锁；以及伯恩-麦基翁综合征（BMKS），其特征为典型的颅面特征（双侧后鼻孔闭锁/狭窄、睑裂短小、下眼睑缺损、鼻梁突出且眼距宽、人中短、上唇红唇薄、耳朵突出）。听力丧失很常见，且有报道称存在心脏缺陷和身材矮小情况。智力残疾罕见。
诊断/检测：通过分子基因检测在具有提示性发现且鉴定出双等位基因致病变异的先证者中确立-相关颅面疾病的诊断。迄今为止所描述的所有先证者在启动子中都至少有两个部分重叠的34bp缺失之一的一个拷贝。
分娩时气道受损的新生儿可能需要插管或对后鼻孔狭窄/闭锁进行手术矫正。可能导致角膜暴露的下眼睑缺陷需要眼科医生护理以降低角膜瘢痕形成的风险。听力丧失的治疗是个体化的，可能包括使用助听器。颅面表现（如唇裂和/或腭裂、耳前赘生物、耳朵突出）的治疗是个体化的，由多学科团队管理。心脏缺陷按常规方式处理。建议由眼科医生、听力学家和颅面团队进行监测。
-相关颅面疾病以常染色体隐性方式遗传。在受孕时，受影响个体的每个同胞有25%的几率受到影响，50%的几率为无症状携带者，25%的几率既不遗传家族性致病基因变异。一旦在受影响的家庭成员中鉴定出致病基因变异，对于风险增加的妊娠可进行产前检测和植入前基因检测。
