Neonatal Intensive Care Unit, Department of Health Promotion, Mother-Child Care, Internal Medicine and Medical Specialties "G. D'Alessandro", University Hospital "P. Giaccone", Via Alfonso Giordano n. 3, 90127, Palermo, Italy.
Pediatric Surgery Unit, Children's Hospital, ARNAS Civico - Di Cristina - Benfratelli, Palermo, Italy.
Ital J Pediatr. 2022 Jul 29;48(1):132. doi: 10.1186/s13052-022-01330-6.
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.
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.
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.
先天性下颌上颌联合是一种罕见的颅面畸形，导致喂养、呼吸和生长困难。融合可能包括软组织联合（粘连）到硬组织联合。孤立的下颌上颌融合病例极为罕见，其病因多为综合征。
介绍了一名女性新生儿的口颌面畸形（粘连、腭裂、颅面发育不良、牙齿异常）和颌面外畸形（覆盖两足足趾指甲的皮肤褶皱、并指、外生殖器异常）的临床处理。相关畸形通过分子遗传学研究发现为干扰素调节因子 6（IRF6）相关疾病（范德沃德综合征/腓肠肌翼综合征）。在染色体 1q32.2 上的 IRF6 基因外显子 4 中发现了一个新的杂合性缺失突变 c.262A>G（p.Asn88Asp）。与同一密码子中已知的天冬酰胺错义突变进行了讨论，这些突变可能通过降低 DNA 结合能力改变 IRF6 基因的功能。同时存在的母性 Xp11.22 重复涉及两个 microRNA 基因，可能导致可能的表观遗传效应。
我们报告的病例携带新的突变，可以帮助扩大对粘连和口面裂形成的分子机制的理解，并正确诊断 IRF6 相关疾病中不完整或重叠的特征。多学科评估以确定 IRF6 相关疾病的表型范围并进行家庭咨询，不仅应集中于粘连和腭裂的手术矫正，还应包括全面的耳鼻喉科、听力学、语言病理学、牙科、矫形科、泌尿科和心理学评估。
