国际口腔医学杂志

国际口腔医学杂志 ›› 2023, Vol. 50 ›› Issue (3): 287-292.doi: 10.7518/gjkq.2023032

• 唇腭裂专栏 • 上一篇    下一篇

Pierre Robin序列征的精准诊断和遗传病因学研究进展

夏溦瑶1(),罗岩坤1,贾仲林2()   

  1. 1.口腔疾病研究国家重点实验室;国家口腔疾病临床医学研究中心;四川大学华西口腔医学院 成都 610041
    2.口腔疾病研究国家重点实验室;国家口腔疾病临床医学研究中心;四川大学华西口腔医院唇腭裂外科 成都 610041
  • 收稿日期:2022-08-20 修回日期:2022-11-16 出版日期:2023-05-01 发布日期:2023-05-16
  • 通讯作者: 贾仲林
  • 作者简介:夏溦瑶，学士，Email：xwy20000615@163.com
  • 基金资助:
    国家自然科学基金面上项目(82170919)

Review of the precise diagnosis and genetic etiology of Pierre Robin sequence

Xia Weiyao1(),Luo Yankun1,Jia Zhonglin2()   

  1. 1.State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu 610041, China
    2.State Key Laboratory of Oral Diseases & Natio-nal Clinical Research Center for Oral Diseases & Dept. of Cleft Lip and Palate Surgery, West China Hospital of Stomato-logy, Sichuan University, Chengdu 610041, China
  • Received:2022-08-20 Revised:2022-11-16 Online:2023-05-01 Published:2023-05-16
  • Contact: Zhonglin Jia
  • Supported by:
    General Program of National Natural Science Foundation of China(82170919)

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摘要：

Pierre Robin序列征是一种具有强烈遗传异质性的先天性颅面畸形，主要表现为小下颌、舌后坠和腭裂，致病基因包括SRY-box转录因子9（SOX9）、内向整流型钾离子通道亚家族J成员2（KCNJ2）、远端同源异型盒5/6（DLX5/6）、白细胞抗原相关家族受体蛋白酪氨酸磷酸酶（LAR RPTPs）和骨形态发生蛋白2（BMP2）等；产前影像检查重点围绕小下颌，宫内舌位和形状可帮助判断。本文主要就该序列征的临床表现、遗传病因和诊断作一综述，明确该疾病的病因和发病机制，并指导产前影像检查方法，为该疾病的精准诊断提供支持。

关键词: Pierre Robin序列征, 先天颅面畸形, 致病基因, 产前诊断

Abstract:

Pierre Robin sequence is a congenital craniofacial anomaly with strong genetic heterogeneity. It mainly mani-fests as micrognathia, retrognathia and cleft palate. Its major pathogenic genes include SRY-box transcription factor 9 (SOX9), potassium inwardly rectifying channel subfamily J member 2 (KCNJ2), distal-less homeobox 5/6 (DLX5/6), leukocyte antigen related receptor protein tyrosine phosphatases (LAR RPTPs), and bone morphogenetic protein 2 (BMP2). Prenatal imaging focuses on micrognathia. However, the position and shape of the tongue in utero may also contribute to the diagnosis of this anomaly. This paper mainly reviews the clinical manifestations, genetic etiology and diagnosis of this sequence sign to clarify its etiology and pathogenesis, guide its prenatal imaging, and provide support for its precise diagnosis of this disease.

Key words: Pierre Robin sequence, congenital craniofacial anomalies, pathogenic gene, prenatal diagnosis

中图分类号: 

  • R 782.2
1 Scott AR, Mader NS. Regional variations in the presentation and surgical management of Pierre Robin sequence[J]. Laryngoscope, 2014, 124(12): 2818-2825.
2 Gomez-Ospina N, Bernstein JA. Clinical, cytogene-tic, and molecular outcomes in a series of 66 patients with Pierre Robin sequence and literature review: 22q11.2 deletion is less common than other chromosomal anomalies[J]. Am J Med Genet, 2016, 170(4): 870-880.
3 Izumi K, Konczal LL, Mitchell AL, et al. Under-lying genetic diagnosis of Pierre robin sequence: retrospective chart review at two children’s hospitals and a systematic literature review[J]. J Pediatr, 2012, 160(4): 645-650.e2.
4 Karempelis P, Hagen M, Morrell N, et al. Associa-ted syndromes in patients with Pierre Robin sequen-ce[J]. Int J Pediatr Otorhinolaryngol, 2020, 131: 109842.
5 孙佳琳, 林岩松, 石冰, 等. 5种常见综合征型唇腭裂遗传学研究进展[J]. 国际口腔医学杂志, 2021, 48(6): 718-724.
Sun JL, Lin YS, Shi B, et al. Research progress on genetics of five common syndromic subtypes of cleft lip and palate[J]. Int J Stomatol, 2021, 48(6): 718-724.
6 McDonald-McGinn DM, Fahiminiya S, Revil T, et al. Hemizygous mutations in SNAP29 unmask autosomal recessive conditions and contribute to atypical findings in patients with 22q11.2DS[J]. J Med Genet, 2013, 50(2): 80-90.
7 Shprintzen RJ. Velo-cardio-facial syndrome: 30 years of study[J]. Dev Disabil Res Rev, 2008, 14(1): 3-10.
8 Wenger TL, Perkins J, Parish-Morris J, et al. Cleft palate morphology, genetic etiology, and risk of mortality in infants with Robin sequence[J]. American J Med Genetics Pt A, 2021, 185(12): 3694-3700.
9 Varadarajan S, Balaji TM, Raj AT, et al. Genetic mutations associated with Pierre Robin syndrome/sequence: a systematic review[J]. Mol Syndromol, 2021, 12(2): 69-86.
10 Jakobsen LP, Ullmann R, Christensen SB, et al. Pierre Robin sequence may be caused by dysregulation of SOX9 and KCNJ2[J]. J Med Genet, 2007, 44(6): 381-386.
11 Benko S, Fantes JA, Amiel J, et al. Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence[J]. Nat Ge-net, 2009, 41(3): 359-364.
12 Tan TY, Farlie PG. Rare syndromes of the head and face-Pierre Robin sequence[J]. Wiley Interdiscip Rev Dev Biol, 2013, 2(3): 369-377.
13 Dash S, Bhatt S, Falcon KT, et al. Med23 regulates Sox9 expression during craniofacial development[J]. J Dent Res, 2021, 100(4): 406-414.
14 Yang RH, Li RY, Huang Z, et al. Mycn deficiency underlies the development of orofacial clefts in mice and humans[J]. Hum Mol Genet, 2022, 31(5): 803-815.
15 Acampora D, Merlo GR, Paleari L, et al. Craniofacial, vestibular and bone defects in mice lacking the distal-less-related gene Dlx5[J]. Development, 1999, 126(17): 3795-3809.
16 Shimizu M, Narboux-Nême N, Gitton Y, et al. Pro-bing the origin of matching functional jaws: roles of Dlx5/6 in cranial neural crest cells[J]. Sci Rep, 2018, 8(1): 14975.
17 Wolf ZT, Leslie EJ, Arzi B, et al. A LINE-1 insertion in DLX6 is responsible for cleft palate and mandibular abnormalities in a canine model of Pierre Robin sequence[J]. PLoS Genet, 2014, 10(4): e1004257.
18 Brown KK, Reiss JA, Crow K, et al. Deletion of an enhancer near DLX5 and DLX6 in a family with hearing loss, craniofacial defects, and an inv(7)(q21.3q35)[J]. Hum Genet, 2009, 127(1): 19-31.
19 Stewart K, Uetani N, Hendriks W, et al. Inactivation of LAR family phosphatase genes Ptprs and Ptprf causes craniofacial malformations resembling Pierre-Robin sequence[J]. Development, 2013, 140(16): 3413-3422.
20 Sahoo T, Theisen A, Sanchez-Lara PA, et al. Microdeletion 20p12.3 involving BMP2 contributes to syndromic forms of cleft palate[J]. Am J Med Genet A, 2011, 155A(7): 1646-1653.
21 Chen YX, Wang ZS, Chen YP, et al. Conditional deletion of Bmp2 in cranial neural crest cells recapitulates Pierre Robin sequence in mice[J]. Cell Tissue Res, 2019, 376(2): 199-210.
22 He FL, Xiong W, Wang Y, et al. Modulation of BMP signaling by Noggin is required for the maintenance of palatal epithelial integrity during palatogenesis[J]. Dev Biol, 2010, 347(1): 109-121.
23 Kim JY, Cho SW, Lee MJ, et al. Inhibition of connexin 43 alters Shh and Bmp-2 expression patterns in embryonic mouse tongue[J]. Cell Tissue Res, 2005, 320(3): 409-415.
24 Wang Y, Zheng YQ, Chen D, et al. Enhanced BMP signaling prevents degeneration and leads to endochondral ossification of Meckel’s cartilage in mice[J]. Dev Biol, 2013, 381(2): 301-311.
25 Yang YJ, Yuan JY, Yao X, et al. BMPR1B mutation causes Pierre Robin sequence[J]. Oncotarget, 2017, 8(16): 25864-25871.
26 Kluivers ACM, Calabrese CE, Koudstaal MJ, et al. Is amniotic fluid level a predictor for syndromic diagnosis in Robin sequence[J]. Cleft Palate Craniofacial J, 2019, 56(6): 773-777.
27 Di Pasquo E, Amiel J, Roth P, et al. Efficiency of prenatal diagnosis in Pierre Robin sequence[J]. Prenat Diagn, 2017, 37(11): 1169-1175.
28 李光荣, 郭斌, 张新荣. Pierre-Robin综合征的CT表现及分型[J]. 中国医学计算机成像杂志, 2014, 20(6): 544-547.
Li GR, Guo B, Zhang XR. Imaging findings and classification of Pierre-Robin syndrome[J]. Chin Comput Med Imag, 2014, 20(6): 544-547.
29 Paladini D, Morra T, Teodoro A, et al. Objective diagnosis of micrognathia in the fetus: the jaw index[J]. Obstet Gynecol, 1999, 93(3): 382-386.
30 Rotten D, Levaillant JM, Martinez H, et al. The fetal mandible: a 2D and 3D sonographic approach to the diagnosis of retrognathia and micrognathia[J]. Ultrasound Obstet Gynecol, 2002, 19(2): 122-130.
31 Palit G, Jacquemyn Y, Kerremans M. An objective measurement to diagnose micrognathia on prenatal ultrasound[J]. Clin Exp Obstet Gynecol, 2008, 35(2): 121-123.
32 Nguyen JQN, Calabrese CE, Heaphy KJ, et al. Can Robin sequence be predicted from prenatal ultrasonography[J]. J Oral Maxillofac Surg, 2020, 78(4): 612-618.
33 Resnick CM, Kooiman TD, Calabrese CE, et al. An algorithm for predicting Robin sequence from fetal MRI[J]. Prenat Diagn, 2018, 38(5): 357-364.
34 Resnick CM, Kooiman TD, Calabrese CE, et al. In utero glossoptosis in fetuses with Robin sequence: measurements from prenatal MRI[J]. Cleft Palate Craniofac J, 2018, 55(4): 562-567.
35 Mouthon L, Busa T, Bretelle F, et al. Prenatal diagnosis of micrognathia in 41 fetuses: retrospective analysis of outcome and genetic etiologies[J]. Am J Med Genet A, 2019, 179(12): 2365-2373.
36 Poets CF, Koos B, Reinert S, et al. The Tübingen palatal plate approach to Robin sequence: summary of current evidence[J]. J Craniomaxillofac Surg, 2019, 47(11): 1699-1705.
37 Inoue M, Ono T, Kameo Y, et al. Forceful mastication activates osteocytes and builds a stout jaw bone[J]. Sci Rep, 2019, 9(1): 4404.
38 Naros A, Krimmel M, Zengerle F, et al. Perioperative complications in cleft palate repair with Robin sequence following Tuebingen palatal plate treatment[J]. J Craniomaxillofac Surg, 2021, 49(4): 298-303.
39 Abbas DB, Lavin C, Fahy EJ, et al. A systematic review of mandibular distraction osteogenesis versus orthodontic airway plate for airway obstruction treatment in Pierre Robin sequence[J]. Cleft Palate Craniofac J, 2022, 59(3): 365-376.
40 Susarla SM, Mundinger GS, Chang CC, et al. Gastrostomy placement rates in infants with Pierre Ro-bin sequence: a comparison of tongue-lip adhesion and mandibular distraction osteogenesis[J]. Plast Reconstr Surg, 2017, 139(1): 149-154.
41 Zhang RS, Hoppe IC, Taylor JA, et al. Surgical ma-nagement and outcomes of Pierre Robin sequence: a comparison of mandibular distraction osteogenesis and tongue-lip adhesion[J]. Plast Reconstr Surg, 2018, 142(2): 480-509.
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