Supplementary Material for: Cleft Lip Palate in a Patient with 5q14.3 Deletion Syndrome: A Possible Unreported Feature?

5q14.3 deletion syndrome (MIM#613443) is an uncommon but well-known syndrome characterized by intellectual disability, epilepsy, hypotonia, brain malformations, and facial dysmorphism. Most patients with this syndrome have lost one copy of the MEF2C gene (MIM*600662), whose haploinsufficiency is considered to be responsible for the distinctive phenotype. To date, nearly 40 cases have been reported; the deletion size and clinical spectrum are variable, and at least 6 cases without MEF2C involvement have been documented. We herein report the clinical and cytogenomic findings of an 11-year-old girl who has a 5q14.3q21.1 de novo deletion that does not involve MEF2C but shares the clinical features described in other reported patients. Moreover, she additionally presents with bilateral cleft-lip palate (CLP), which has not been previously reported as a feature of the syndrome. The most frequent syndromic forms of CLP were ruled out in our patient mainly by clinical examination, and Sanger sequencing was performed to discard the presence of a TBX22 gene (MIM*300307) defect. Our report suggests CLP as a possible unreported feature and redefines the critical phenotypic regions of 5q14.3 deletion syndrome.5q14.3缺失综合征（MIM#613443）是一种少见但已被充分认知的综合征，以智力障碍、癫痫、肌张力低下、脑畸形及面部形态异常为主要临床特征。该综合征的绝大多数患者存在MEF2C基因（MIM*600662）的单拷贝缺失，该基因的单倍剂量不足被认为是导致其特征性表型的致病基础。截至目前，全球已报道近40例该综合征病例；其缺失片段大小及临床表型谱均存在异质性，且至少有6例未累及MEF2C基因的病例被文献记录。本文报道1例11岁女性患者的临床及细胞基因组学特征：该患者携带5q14.3q21.1新发缺失，该缺失未累及MEF2C基因，但具备其他已报道病例的典型临床表型。此外，该患者还合并双侧唇腭裂（bilateral cleft-lip palate, CLP），此表型此前未被纳入该综合征的临床特征范畴。本研究主要通过临床检查排除了该患者最常见的综合征型唇腭裂病因，并通过桑格测序（Sanger sequencing）排除了TBX22基因（MIM*300307）缺陷的可能。本研究提示双侧唇腭裂可能是该综合征尚未被报道的临床表型之一，并重新界定了5q14.3缺失综合征的关键表型区域。