背景:先天性上颌下颌联合症是一种罕见的颅面畸形,导致进食困难,呼吸和茁壮成长的能力。融合可以由软组织结合(粘连)到硬组织结合组成。孤立的上颌下颌融合术极为罕见,它通常是病因综合征。
方法:患有口腔颌面畸形的女性新生儿的临床处理(synechiae,腭裂,颅面畸形,牙齿异常)和口外畸形(皮褶覆盖两个幻觉的指甲,齐体,外生殖器异常)。针对分子遗传学研究的相关畸形揭示了干扰素调节因子6(IRF6)相关疾病(vanderWoude综合征/pop翼状胬肉综合征)。1q32.2号染色体IRF6基因外显子4中的一种新的从头杂合突变,确切地说是c.262A>G(p。Asn88Asp),找到了。与相同密码子中已知的天冬酰胺错义突变进行了相似性讨论,这可能通过降低DNA结合能力来改变IRF6基因功能。伴随的涉及两个microRNA基因的母体Xp11.22重复可能导致可能的表观遗传效应。
结论:我们报道的携带新突变的病例有助于扩大对粘连和口面裂开的分子机制的理解,并有助于正确诊断IRF6相关疾病的不完整或重叠特征。建立IRF6相关疾病的表型范围并解决家庭咨询的其他多学科评估不仅应集中在手术矫正的手术上。但也涉及全面的耳鼻喉科,听力学,logopedic,牙科,骨科,泌尿科和心理评估。
BACKGROUND: Congenital maxillomandibular
syngnathia is a rare craniofacial anomaly leading to difficulties in feeding, breathing and ability to thrive. The fusion may consist of soft tissue union (synechiae) to hard tissue union. Isolated cases of maxillomandibular fusion are extremely rare, it is most often syndromic in etiology.
METHODS: Clinical management of a female newborn with oromaxillofacial abnormities (synechiae, cleft palate, craniofacial dysmorphisms, dental anomaly) and extraoral malformations (skinfold overlying the nails of both halluces, syndactyly, abnormal external genitalia) is presented. The associated malformations addressed to molecular genetic investigations revealing an interferon regulatory factor 6 (IRF6)-related disorder (van der Woude syndrome/popliteal pterygium syndrome). A novel de novo heterozygous mutation in exon 4 of IRF6 gene on chromosome 1q32.2, precisely c.262A > G (p.Asn88Asp), was found. Similarities are discussed with known asparagine missense mutations in the same codon, which may alter IRF6 gene function by reduced DNA-binding ability. A concomitant maternal Xp11.22 duplication involving two microRNA genes could contribute to possible epigenetic effects.
CONCLUSIONS: Our reported case carrying a novel mutation can contribute to expand understandings of molecular mechanisms underlying synechiae and orofacial clefting and to correct diagnosing of incomplete or overlapping features in IRF6-related disorders. Additional multidisciplinary evaluations to establish the phenotypical extent of the IRF6-related disorder and to address family counseling should not only be focused on the surgical corrections of
syngnathia and cleft palate, but also involve comprehensive otolaryngologic, audiologic, logopedic, dental, orthopedic, urological and psychological evaluations.